70 results on '"Tatiana Tzenou"'
Search Results
2. Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia
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Katerina Sarris, Dimitrios Maltezas, Efstathios Koulieris, Vassiliki Bartzis, Tatiana Tzenou, Sotirios Sachanas, Eftychia Nikolaou, Anna Efthymiou, Katerina Bitsani, Maria Dimou, Theodoros P. Vassilakopoulos, Marina Siakantaris, Maria K. Angelopoulou, Flora Kontopidou, Panagiotis Tsaftaridis, Nikolitsa Kafasi, Gerasimos A. Pangalis, Panayiotis P. Panayiotidis, Stephen Harding, and Marie-Christine Kyrtsonis
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients. Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients’ series. Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients’ followup was 32 months (range 4–228). Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P=0.0005 and P=0.000003, resp.) and overall survival (P=0.05 and P=0.003, resp.). They also correlated with β2-microglobulin (P=0.009 and P=0.03, resp.), serum albumin (P=0.009 for summated sFLC), hemoglobin (P
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- 2013
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3. Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib
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Konstantinos Anargyrou, Evangelos Terpos, Theodoros P. Vassilakopoulos, Anastasia Pouli, Sotirios Sachanas, Tatiana Tzenou, Stavroula Masouridis, Dimitrios Christoulas, Maria K. Angelopoulou, Evangelia M. Dimitriadou, Christina Kalpadakis, Konstantinos Tsionos, Panayiotis Panayiotidis, Meletios A. Dimopoulos, Gerassimos A. Pangalis, and Marie-Christine Kyrtsonis
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Neoangiogenesis is involved in the pathophysiology of multiple myeloma and angiopoietins possibly contribute to myeloma-induced neovascularization. Bortezomib’s antineoplastic potential includes an anti-angiogenic effect. We determined serum levels of angiopoietin-1 and angiopoietin-2 with ELISA pre- and post-bortezomib administration in 35 patients with relapsed/refractory multiple myeloma. Pre-bortezomib, serum angiopoietin-1 levels did not differ in patients and in healthy individuals, while serum angiopoietin-2 levels were elevated. Corresponding serum angiopoietin-1/angiopoietin-2 ratio was reduced in patients compared with controls. After treatment, serum angiopoietin-1 levels increased, while serum angiopoietin-2 levels decreased, therefore the angiopoietin-1/angiopoietin-2 ratio increased and normalized. This increase was significant in patients who responded to treatment. In conclusion, angiopoietin-1/angiopoietin-2 ratio normalization reflected response to bortezomib.
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- 2008
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4. Figure S1 from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
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Kostas Stamatopoulos, Paolo Ghia, Richard Rosenquist, Anastasia Hadzidimitriou, Frederic Davi, Chrysoula Belessi, Nikos Darzentas, Ioanna Chouvarda, Stephan Stilgenbauer, Diane F. Jelinek, Gianluca Gaidano, David Oscier, Nikos Maglaveras, Nicholas Chiorazzi, Elias Campo, Michael Hallek, Sarka Pospisilova, Anton W. Langerak, Hartmut Döhner, Carsten Niemann, Marco Montillo, Livio Trentin, Darko Antic, Ioannis Vlahavas, Achilles Anagnostopoulos, Gunnar Juliusson, Panagiotis Panagiotidis, Marie-Paule Lefranc, Véronique Giudicelli, Charles C. Chu, Karin E. Smedby, Larry Mansouri, Lone Bredo Pedersen, Christiane Pott, Jasmin Bahlo, Monica Facco, Maria Chatzouli, Dirk Kienle, Mark Catherwood, Teodora Karan-Djurasevic, Tatiana Tzenou, Silvio Veronese, Andrey Sudarikov, Niki Stavroyianni, Lydia Scarfo, Fie Juhl Vojdeman, Yorick Sandberg, Alba Navarro, Zadie Davis, Davide Rossi, Myriam Boudjogra, Karla Plevova, Tait Shanafelt, Xiao-Jie Yan, Eugen Tausch, Stavroula Ntoufa, Eva Minga, Lesley-Ann Sutton, Andreas Agathangelidis, Ioannis Kavakiotis, Panagiotis Baliakas, and Aliki Xochelli
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Distribution of IGHV4-34 CLL according to IGHV mutational status and subset membership.
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- 2023
5. Data from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
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Kostas Stamatopoulos, Paolo Ghia, Richard Rosenquist, Anastasia Hadzidimitriou, Frederic Davi, Chrysoula Belessi, Nikos Darzentas, Ioanna Chouvarda, Stephan Stilgenbauer, Diane F. Jelinek, Gianluca Gaidano, David Oscier, Nikos Maglaveras, Nicholas Chiorazzi, Elias Campo, Michael Hallek, Sarka Pospisilova, Anton W. Langerak, Hartmut Döhner, Carsten Niemann, Marco Montillo, Livio Trentin, Darko Antic, Ioannis Vlahavas, Achilles Anagnostopoulos, Gunnar Juliusson, Panagiotis Panagiotidis, Marie-Paule Lefranc, Véronique Giudicelli, Charles C. Chu, Karin E. Smedby, Larry Mansouri, Lone Bredo Pedersen, Christiane Pott, Jasmin Bahlo, Monica Facco, Maria Chatzouli, Dirk Kienle, Mark Catherwood, Teodora Karan-Djurasevic, Tatiana Tzenou, Silvio Veronese, Andrey Sudarikov, Niki Stavroyianni, Lydia Scarfo, Fie Juhl Vojdeman, Yorick Sandberg, Alba Navarro, Zadie Davis, Davide Rossi, Myriam Boudjogra, Karla Plevova, Tait Shanafelt, Xiao-Jie Yan, Eugen Tausch, Stavroula Ntoufa, Eva Minga, Lesley-Ann Sutton, Andreas Agathangelidis, Ioannis Kavakiotis, Panagiotis Baliakas, and Aliki Xochelli
- Abstract
Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication.Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34–expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes.Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively).Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. Clin Cancer Res; 23(17); 5292–301. ©2017 AACR.
- Published
- 2023
6. Table S1 from Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
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Kostas Stamatopoulos, Paolo Ghia, Richard Rosenquist, Anastasia Hadzidimitriou, Frederic Davi, Chrysoula Belessi, Nikos Darzentas, Ioanna Chouvarda, Stephan Stilgenbauer, Diane F. Jelinek, Gianluca Gaidano, David Oscier, Nikos Maglaveras, Nicholas Chiorazzi, Elias Campo, Michael Hallek, Sarka Pospisilova, Anton W. Langerak, Hartmut Döhner, Carsten Niemann, Marco Montillo, Livio Trentin, Darko Antic, Ioannis Vlahavas, Achilles Anagnostopoulos, Gunnar Juliusson, Panagiotis Panagiotidis, Marie-Paule Lefranc, Véronique Giudicelli, Charles C. Chu, Karin E. Smedby, Larry Mansouri, Lone Bredo Pedersen, Christiane Pott, Jasmin Bahlo, Monica Facco, Maria Chatzouli, Dirk Kienle, Mark Catherwood, Teodora Karan-Djurasevic, Tatiana Tzenou, Silvio Veronese, Andrey Sudarikov, Niki Stavroyianni, Lydia Scarfo, Fie Juhl Vojdeman, Yorick Sandberg, Alba Navarro, Zadie Davis, Davide Rossi, Myriam Boudjogra, Karla Plevova, Tait Shanafelt, Xiao-Jie Yan, Eugen Tausch, Stavroula Ntoufa, Eva Minga, Lesley-Ann Sutton, Andreas Agathangelidis, Ioannis Kavakiotis, Panagiotis Baliakas, and Aliki Xochelli
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Univariable and multivariable analysis for TTFT within M-CLL.
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- 2023
7. Novel M-Component Based Biomarkers in Waldenström's Macroglobulinemia
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Leleu, Xavier, Koulieris, Efstathios, Maltezas, Dimitrios, Itzykson, Raphael, Xie, Wanling, Manier, Salomon, Dulery, Remy, Boyle, Eilleen, Gauthier, Jordan, Poulain, Stéphanie, Tatiana, Tzenou, Panayiotidis, Panayiotis, Bradwell, Arthur R., Harding, Stephen, Leblond, Veronique, Kyrtsonis, Marie-Christine, and Ghobrial, Irene M.
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- 2011
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8. MANTLE CELL LYMPHOMA, A SINGLE CENTER EXPERIENCE
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M Bouzani, G Tounta, Stavros Gigantes, V Babali, Dimitra Rontogianni, I Tsonis, I Darmani, A Roumelioti, P Kosmas, K Kaouranis, D Ikonopoulou, M Dellatola, E Andreou, M. Bakiri, K. Sakellariou, F Karaolidou, D Gardeli, A Loutsidi, E.-K Dimitraki, Z Mellios, K Souravla, G Kanellis, N El-Gkotmi, C Giatra, Tatiana Tzenou, Ioannis Baltadakis, D Karakasis, L Ligdi, and Themistoklis Karmiris
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Cancer Research ,Oncology ,Cancer research ,medicine ,Mantle cell lymphoma ,Hematology ,General Medicine ,Single Center ,medicine.disease ,Geology - Published
- 2021
9. Chimeric Antigen Receptor T Cells for Refractory/Relapsed Diffuse Large B Cell Lymphoma and Acute Lymphoblastic Leukemia: The Hellenic Real-World Experience in Adult Patients
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Eleni Gavriilaki, Ifigeneia Tzannou, Stavros Gigantes, Tatiana Tzenou, Ioanna Sakellari, Ioannis Batsis, Thomas Chatzikonstantinou, Achilles Anagnostopoulos, Damianos Sotiropoulos, Ioannis Tsonis, Christos Varelas, Dimitrios Karakasis, Ioannis Baltadakis, Despina Mallouri, and Maria Bouzani
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Adult patients ,business.industry ,Lymphoblastic Leukemia ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Chimeric antigen receptor ,Refractory ,Cancer research ,Medicine ,business ,Diffuse large B-cell lymphoma - Abstract
Introduction: Immunotherapy with Chimeric Antigen Receptor T cells (CAR-Τ) is a promising innovative treatment for refractory B cell malignancies offering a considerable chance for long-term survival in patients (pts) with an otherwise dismal prognosis. Since January 2020, two anti-CD19 CAR T cell products have been introduced into clinical practice in Greece: a) tisagenlecleucel (Kymriah) for adults with relapsed/refractory diffuse large B-cell Lymphoma (r/r DLBCL) including transformed follicular lymphoma (TFL), as well as for children or young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL), and b) axicabtagene ciloleucel (Yescarta) for adults with r/r DLBCL including TFL and primary mediastinal B-cell lymphoma (PMBCL). The aim of this study was to present the real-world experience of the initial application of CAR T cell therapy in adult pts in Greece, with special focus on early toxicity and disease outcomes. Methods: Data from all consecutive pts were collected from the two transplant centers which were initially accredited for CAR T cell therapies in adult pts: Evangelismos Hospital, Athens and George Papanicolaou Hospital, Thessaloniki. Between November 2019 and July 2021, 51 pts were referred for CAR T cell treatment. In 41 pts lymphocyte collection was performed and product manufacturing was successfully completed in 35; in 2 pts insufficient cell expansion was noted and in 4 manufacturing was terminated due to disease progression and patient death. Results: From January 2020 until July 2021, CAR T cells were infused in 27 pts; 3 pts could not receive the product due to clinical deterioration/death and 5 pts are presently being scheduled for infusion. Of the 27 treated pts, 16 received tisagenlecleucel and 11 axicabtagene ciloleucel. The median age of infused pts was 49 (18-69) years. Diagnosis was DLBCL (n=16), PMBCL (n=3), TFL (n=2), B-ALL (n=6), and the median number of previous lines of treatment was 4 (2-5). Five pts with lymphoma had undergone autologous, and 4 pts with B-ALL allogeneic stem cell transplantation. In total 18/27 pts received bridging therapy, including radiotherapy (n=5), chemoimmunotherapy (n=9), steroids (n=3), and inotuzumab ozogamicin (n=1). The median time from leukapheresis to product delivery and infusion was 35 (15-81) and 59 (35-152) days, respectively. All pts received lymphodepleting therapy before CAR T cell infusion with combination of cyclophosphamide and fludarabine. For patient monitoring, prophylactic therapy and management of toxicity, the EBMT (Yakoub-Agha I, et al. Haematologica 2020) and MD Anderson (Neelapu S, et al. Nat Rev Clin Oncol 2018) guidelines were adopted. Twenty-six pts developed neutropenia (grade II: 2, grade IV: 24) and 20 thrombocytopenia (grade I: 7, grade II: 3, grade III: 1, grade IV: 9), with a median duration of 11 (4-132) and 20 (3-150) days, respectively. Cytokine release syndrome (CRS) and neurotoxicity (ICANS) were noted in 21 (grade I: 8, grade II: 7, grade III: 6) and 5 (grade I: 3, grade III: 2) pts, respectively. Tocilizumab was administered for CRS according to guidelines, and steroids were additionally required for CRS and/or ICANS in 12 pts. In 2 pts, persistent ICANS necessitated further treatment with anakinra (n=2), siltuximab (n=1), and cyclophosphamide (n=1). Hypogammaglobulinemia was encountered in 14/27 pts. With a median follow-up of 7.3 (1-17) months, overall response rate was 48% with 12 (45%) pts being currently in complete remission (CR). No treatment related mortality was observed. Disease-free (DFS) and overall survival (OS) were 52% and 85.3% at 1-year, respectively. DFS and OS were significantly associated with baseline LDH levels (p=0.017 and 0.050, respectively) and grade II/III CRS (p=0.041 and 0.015, respectively, Figure). Conclusions: Despite the limited experience in the real-world setting, CAR T cell therapy can be administered safely and may successfully rescue patients with DLBCL or B-ALL who lack alternative treatment options. Close monitoring of patients and prompt recognition and management of side effects are mandatory for achieving the benefits of therapy. Figure 1 Figure 1. Disclosures Baltadakis: WinMedica: Other: Travel Grants; Gilead: Other: Travel Grants; Genesis Pharma: Other: Travel Grants; Abbvie: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Pfizer: Honoraria, Other: Travel Grants; Astellas: Honoraria; Alexion: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Baxalta Hellas: Other: Travel Grants. Gavriilaki: Pfizer Corporation: Research Funding; Gilead Corporation: Honoraria; Alexion, Omeros, Sanofi Corporation: Consultancy. Tzannou: Allovir: Current equity holder in publicly-traded company; Gileas: Honoraria. Anagnostopoulos: Abbvie: Other: clinical trials; Sanofi: Other: clinical trials ; Ocopeptides: Other: clinical trials ; GSK: Other: clinical trials; Incyte: Other: clinical trials ; Takeda: Other: clinical trials ; Amgen: Other: clinical trials ; Janssen: Other: clinical trials; novartis: Other: clinical trials; Celgene: Other: clinical trials; Roche: Other: clinical trials; Astellas: Other: clinical trials .
- Published
- 2021
10. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
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Véronique Giudicelli, Lesley-Ann Sutton, Panagiotis Baliakas, Anastasia Hadzidimitriou, David Oscier, Kostas Stamatopoulos, Michael Hallek, Eugen Tausch, Marco Montillo, Achilles Anagnostopoulos, Elias Campo, Yorick Sandberg, Silvio Veronese, Šárka Pospíšilová, Dirk Kienle, Karin E. Smedby, Xiao-Jie Yan, Lydia Scarfò, Andreas Agathangelidis, Nikos Darzentas, Richard Rosenquist, Stavroula Ntoufa, Larry Mansouri, Darko Antic, Niki Stavroyianni, Aliki Xochelli, Tait D. Shanafelt, Tatiana Tzenou, Andrey Sudarikov, Charles C. Chu, Anton W. Langerak, Marie-Paule Lefranc, Nicholas Chiorazzi, Eva Minga, Carsten Utoft Niemann, Ioanna Chouvarda, Nikos Maglaveras, Gianluca Gaidano, Maria Chatzouli, Karla Plevová, Mark Catherwood, Hartmut Döhner, Chrysoula Belessi, Myriam Boudjogra, Zadie Davis, Ioannis Kavakiotis, Gunnar Juliusson, Livio Trentin, Frederic Davi, Davide Rossi, Jasmin Bahlo, Diane F. Jelinek, Monica Facco, Christiane Pott, Lone Bredo Pedersen, Panagiotis Panagiotidis, Fie Juhl Vojdeman, Stephan Stilgenbauer, Teodora Karan-Djurasevic, Alba Navarro, Paolo Ghia, Ioannis Vlahavas, Immunology, Xochelli, Aliki, Baliakas, Panagioti, Kavakiotis, Ioanni, Agathangelidis, Andrea, Sutton, Lesley-Ann, Minga, Eva, Ntoufa, Stavroula, Tausch, Eugen, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey, Veronese, Silvio, Tzenou, Tatiana, Karan-Djurasevic, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pott, Christiane, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E, Chu, Charles C, Giudicelli, Véronique, Lefranc, Marie-Paule, Panagiotidis, Panagioti, Juliusson, Gunnar, Anagnostopoulos, Achille, Vlahavas, Ioanni, Antic, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Döhner, Hartmut, Langerak, Anton W, Pospisilova, Sarka, Hallek, Michael, Campo, Elia, Chiorazzi, Nichola, Maglaveras, Niko, Oscier, David, Gaidano, Gianluca, Jelinek, Diane F, Stilgenbauer, Stephan, Chouvarda, Ioanna, Darzentas, Niko, Belessi, Chrysoula, Davi, Frederic, Hadzidimitriou, Anastasia, Rosenquist, Richard, Ghia, Paolo, and Stamatopoulos, Kostas
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Male ,0301 basic medicine ,Cancer Research ,Chronic lymphocytic leukemia ,B-cell receptor ,Immunoglobulin Variable Region ,Somatic hypermutation ,Immunogenetics ,Disease ,Biology ,03 medical and health sciences ,hemic and lymphatic diseases ,medicine ,Humans ,Amino Acid Sequence ,breakpoint cluster region ,Chronic Lymphocytic Leukemia B cell receptor BCR Immunoglobulin ,medicine.disease ,ADP-ribosyl Cyclase 1 ,Leukemia, Lymphocytic, Chronic, B-Cell ,3. Good health ,Gene Expression Regulation, Neoplastic ,Leukemia ,030104 developmental biology ,Oncology ,Immunology ,biology.protein ,Female ,Somatic Hypermutation, Immunoglobulin ,Antibody ,Immunoglobulin Heavy Chains - Abstract
Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34–expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. Clin Cancer Res; 23(17); 5292–301. ©2017 AACR.
- Published
- 2017
11. Viral Reactivation after T Cell Replete Haploidentical Stem Cell Transplantation: Increased Incidence in Association with Immune Reconstitution
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Maria Bouzani, Zois Mellios, Maria Katsareli, Tatiana Tzenou, Dimitris Karakasis, Dimitra Oikonomopoulou, Chara Giatra, Ioannis Baltadakis, Dimitra Gardeli, Stavros Gigantes, Ioannis Tsonis, Themistoklis Karmiris, Maria-Eleni Karatza, and Eirini Grispou
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Transplantation ,medicine.medical_specialty ,Cellular immunity ,Myeloid ,Cyclophosphamide ,business.industry ,Hematology ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,BK virus ,Letermovir ,medicine.anatomical_structure ,Internal medicine ,medicine ,Rituximab ,business ,Hemorrhagic cystitis ,medicine.drug - Abstract
Feasibility of haploidentical stem cell transplantation (haploSCT) is enhanced by use of post-transplant cyclophosphamide (PTCY). Despite preservation of non-alloreactive T cells, delayed reconstitution of cellular immunity and viral reactivation may compromise the outcome of T cell replete haploSCT. The study included 47 patients, aged 19-70 (median, 53) years, who underwent haploSCT with PTCY for myeloid (n=35) or lymphoid (n=12) malignancies. Myeloablative conditioning was mainly utilized (n=36). Graft source was peripheral blood (n=29) or bone marrow (n=18). Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood in cases with hemorrhagic cystitis (HC). Preemptive therapy was the principal modality for CMV infection in all but 1 patient who received letermovir prophylaxis. Reconstitution of cellular immunity was assessed by flow cytometry. With a median follow-up of 30 months, cumulative incidences (CIN) of relapse and non-relapse mortality were 13.4% (95% CI, 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free and overall survival were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. CIN of CMV reactivation (>100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34/45 patients at risk. Recurrent CMV infection occurred in 17/34 with median 1.5 (range, 1-6) episodes per patient. Median duration of anti-CMV therapy was 27 (range, 14-199) days. CMV disease was documented in 2 patients. CIN of EBV reactivation (>1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 1 year, and preemptive therapy with rituximab was required in 2 patients. HHV-6 reactivation (>1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%). CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy was required in 5/13 and nephrostomy in 1/13 patients. Reconstitution of T cell immunity was considerably delayed, with median CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was associated with the recovery of CD4+ cells at 3 months (Figure, median CD4+ count of 191/uL versus 62/uL in patients with 1 or ³2 episodes of CMV reactivation, respectively; p=0.009). Haplo-SCT with PTCY is associated with substantial rates of viral reactivation resulting in the need for prolonged antiviral therapy and considerable morbidity as well. Strategies to prevent viral infection are strongly warranted. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution.
- Published
- 2020
12. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy
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Tatiana Tzenou, Richard Rosenquist, Marie-Paule Lefranc, Karla Plevová, Charles C. Chu, Yorick Sandberg, Gunnar Juliusson, Véronique Giudicelli, Livio Trentin, Mark Catherwood, Frederic Davi, Šárka Pospíšilová, Xiao-Jie Yan, Silvio Veronese, Lesley-Ann Sutton, Carsten Utoft Niemann, Nikos Darzentas, Kostas Stamatopoulos, Achilles Anagnostopoulos, Diane F. Jelinek, David Oscier, Mattias Mattsson, Nicholas Chiorazzi, Karin E. Smedby, Panagiotis Panagiotidis, Chrysoula Belessi, Florence Nguyen-Khac, Marco Montillo, Eva Minga, Paolo Ghia, Anton W. Langerak, Lydia Scarfò, Andreas Agathangelidis, Tait D. Shanafelt, Panagiotis Baliakas, Niki Stavroyianni, Larry Mansouri, Anastasia Hadzidimitriou, Zadie Davis, Fie Juhl Vojdeman, Uppsala Universitet [Uppsala], Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Department of Immunology, Genetics and Pathology [Uppsala, Sueden] (IGP), Uppsala University, Department of Hematology [Uppsala], Università Vita-Salute San Raffaele, Milan, Italy., Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden, Università Vita e Salute, San Raffaele, Milano, Italy, Strategic Research Program in CLL, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy., Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK., The Feinstein Institute for Medical Research, CEITEC-Central European Institute of Technology, MasarykBrno, Czech Republic., Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Hematology, Rigshospitalet, Copenhagen, Denmark, First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, and Hematology Center, Karolinska University Hospital, Stockholm, Sweden, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hematology and Transplantation, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece, Universita degli Studi di Padova, Venetian Institute Molecular Medicine (VIMM), Department of Hemato-Oncology, Belfast City Hospital, Belfast, UK, University Hospital Brno, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Immunology, Mayo Clinic, Rochester, MV, USA, Mayo Clinic [Rochester], Hematology Department, Nikea General Hospital, Piraeus, Greece, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden., Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece., Institute of Applied Biosciences, Thessaloniki, Greece., Department of Immunology, Baliakas, Panagioti, Mattsson, Mattia, Hadzidimitriou, Anastasia, Minga, Eva, Agathangelidis, Andrea, Sutton, Lesley-Ann, Scarfo, Lydia, Davis, Zadie, Yan, Xiao-Jie, Plevova, Karla, Sandberg, Yorick, Vojdeman, Fie J, Tzenou, Tatiana, Chu, Charles C, Veronese, Silvio, Mansouri, Larry, Smedby, Karin E, Giudicelli, Véronique, Nguyen-Khac, Florence, Panagiotidis, Panagioti, Juliusson, Gunnar, Anagnostopoulos, Achille, Lefranc, Marie-Paule, Trentin, Livio, Catherwood, Mark, Montillo, Marco, Niemann, Carsten U, Langerak, Anton W, Pospisilova, Sarka, Stavroyianni, Niki, Chiorazzi, Nichola, Oscier, David, Jelinek, Diane F, Shanafelt, Tait, Darzentas, Niko, Belessi, Chrysoula, Davi, Frederic, Ghia, Paolo, Rosenquist, Richard, Stamatopoulos, Kostas, and Immunology
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Adult ,Male ,chemorefractorine ,Oncology ,medicine.medical_specialty ,Cyclophosphamide ,Chronic lymphocytic leukemia ,[SDV]Life Sciences [q-bio] ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Drug Therapy ,Chemoimmunotherapy ,Internal medicine ,medicine ,Humans ,Chronic Lymphocytic Leukemia ,[INFO]Computer Science [cs] ,stereotyped subsets ,Online Only Articles ,Survival rate ,ComputingMilieux_MISCELLANEOUS ,Aged ,Retrospective Studies ,Aged, 80 and over ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Hematology ,business.industry ,Middle Aged ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,3. Good health ,Fludarabine ,Survival Rate ,Leukemia ,030220 oncology & carcinogenesis ,Female ,Rituximab ,Immunotherapy ,business ,030215 immunology ,medicine.drug - Abstract
The overall survival (OS) of patients with chronic lymphocytic leukemia (CLL) has improved over the last decades mainly due to advances in the understanding of the disease biology and the introduction of novel therapeutic approaches(1). In the present retrospective study we investigated trends in OS in subgroups of cases defined by genetic and immunogenetic features aiming at addressing the question whether advances in chemoimmunotherapy had a uniform impact across all CLL patients. We found that such advances have translated into prolonged OS in all prognostic subgroups examined except those carrying TP53 abnormalities, as expected, but also those assigned to stereotyped subsets #1 and #2, that are generally devoid of such gene aberrations. This latter finding, reported here for the first time, indicates the need for alternative treatment options for these patients.
- Published
- 2018
13. Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations
- Author
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Eva Minga, Karin E. Smedby, Lesley-Ann Sutton, Nicholas Chiorazzi, Myriam Boudjogra, Kostas Stamatopoulos, Karla Plevová, Lone Bredo Pedersen, Zadie Davis, Lydia Scarfò, Andreas Agathangelidis, Monica Facco, Achilles Anagnostopoulos, Maria Chatzouli, Chrysoula Belessi, Athina Tsanousa, Panagiotis Baliakas, Kirsten van Lom, Lefteris Angelis, Yorick Sandberg, Gunnar Juliusson, Diane F. Jelinek, Fie Juhl Vojdeman, Anne Gardiner, Panagiotis Panagiotidis, Anton W. Langerak, Florence Nguyen-Khac, Hana Skuhrová Francová, Frederic Davi, Denis Moreno, Silvio Veronese, Richard Rosenquist, Marie-Paule Lefranc, Nikos Darzentas, Šárka Pospíšilová, Véronique Giudicelli, Xiao-Jie Yan, Charles C. Chu, Christian H. Geisler, Larry Mansouri, David Oscier, Mark Catherwood, Marco Montillo, Anastasia Hadzidimitriou, Livio Trentin, Paolo Ghia, Tait D. Shanafelt, Tatiana Tzenou, Baliakas, P, Agathangelidis, A, Hadzidimitriou, A, Sutton, La, Minga, E, Tsanousa, A, Scarfò, L, Davis, Z, Yan, Xj, Shanafelt, T, Plevova, K, Sandberg, Y, Vojdeman, Fj, Boudjogra, M, Tzenou, T, Chatzouli, M, Chu, Cc, Veronese, S, Gardiner, A, Mansouri, L, Smedby, Ke, Pedersen, Lb, Moreno, D, Van Lom, K, Giudicelli, V, Francova, H, Nguyen Khac, F, Panagiotidis, P, Juliusson, G, Angelis, L, Anagnostopoulos, A, Lefranc, Mp, Facco, M, Trentin, L, Catherwood, M, Montillo, M, Geisler, Ch, Langerak, Aw, Pospisilova, S, Chiorazzi, N, Oscier, D, Jelinek, Df, Darzentas, N, Belessi, C, Davi, F, Ghia, PAOLO PROSPERO, Rosenquist, R, Stamatopoulos K. Ghia P., is Co senior author, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Università Vita-Salute San Raffaele, Milan, Italy, Division of Molecular Oncology and Department of Onco-Hematology, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy, Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Department of Informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece, Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom, The Feinstein Institute for Medical Research, Mayo Clinic [Rochester], Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Hematology, Rigshospitalet, Copenhagen, Denmark, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Hematology Department, Nikea General Hospital, Piraeus, Greece, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Hematology Department and Hematopoietic Cell Transplantation Unit, Georgios Papanicolaou Hospital, Thessaloniki, Greece, Universita degli Studi di Padova, Department of Hemato-Oncology, Belfast City Hospital, Belfast, United Kingdom, Immunology, and Hematology
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Male ,Oncology ,medicine.medical_specialty ,Chronic lymphocytic leukemia ,Immunology ,B-cell receptor ,Gene Rearrangement, B-Lymphocyte, Heavy Chain ,Antineoplastic Agents ,Biology ,Biochemistry ,Time-to-Treatment ,Genetic Heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,10. No inequality ,ComputingMilieux_MISCELLANEOUS ,Survival analysis ,Aged ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,B-Lymphocytes ,0303 health sciences ,Lymphoid Neoplasia ,Hematology ,Gene Expression Regulation, Leukemic ,Genetic heterogeneity ,Cell Biology ,Middle Aged ,Prognosis ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Survival Analysis ,Treatment Outcome ,030220 oncology & carcinogenesis ,biology.protein ,Immunoglobulin heavy chain ,Female ,Somatic Hypermutation, Immunoglobulin ,Antibody ,Immunoglobulin Heavy Chains ,IGHV@ - Abstract
An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset # 2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset # 2. Within subset # 2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset # 2/IGHV3-21 was enriched for IGHV-unmutated cases (P =.002). Subset # 2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset # 2/IGHV3-21 (22 vs 60 months, P =.001). No such difference was observed between non-subset # 2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset # 2 emerges as uniformly aggressive, contrasting non-subset # 2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.
- Published
- 2015
14. Aberrant Immunoglobulin Variations as Indicators of Eventual Clonal Changes in Symptomatic Multiple Myeloma Patients' Course
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Efstathios Koulieris, Panagiotis Tsaftaridis, Maria M. Angelopoulou, Ioanna Vardounioti, Eftychia Nikolaou, Aikaterini Bitsani, Marie-Christine Kyrtsonis, Maria Dimou, Theodoros P. Vassilakopoulos, Anna Efthymiou, Dimitrios Maltezas, Nikolitsa Kafasi, Theodoros Iliakis, Panayiotis Panayiotidis, Vasiliki Bartzis, Vasiliki Karali, Tatiana Tzenou, Aikaterini Sarris, Ilias Pessach, Kalliroi Tsalimalma, and Nora-Athina Vyniou
- Subjects
Cancer Research ,Oncology ,biology ,business.industry ,Immunology ,medicine ,biology.protein ,Molecular Medicine ,Antibody ,medicine.disease ,business ,Multiple myeloma - Published
- 2014
15. The Role of CXC-Chemokine IL-8, IL-6 and CXCR2 Receptor in Lymphoplasmacytic Lymphoma: Correlations with Microvascular Characteristics and Clinical Features
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Katerina Bitsanis, Tatiana Tzenou, Marie-Christine Kyrtsonis, Dimitris Maltezas, Panayiotis Panayiotidis, Nikolaos Kavantzas, Ilias Pessach, Eftychia Nikolaou, Efstathios Koulieris, Gerassimos A. Pangalis, Penelope Korkolopoulou, Georgia Levidou, Katerina Xirokosta, Maria Dimou, Vassiliki Bartzis, Athanasia Sepsa, and Efstratios Patsouris
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,biology ,business.industry ,Lymphoplasmacytic Lymphoma ,Oncology ,CxC chemokine ,Immunology ,biology.protein ,medicine ,CXC chemokine receptors ,Interleukin 8 ,Receptor ,Interleukin 6 ,business - Published
- 2014
16. Increased Incidence of Viral Reactivation after T Cell Replete Haploidentical Stem Cell Transplantation in Association with Delayed Immune Reconstitution
- Author
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Tatiana Tzenou, Maria Bouzani, Ioannis Tsonis, Chara Giatra, Ioannis Baltadakis, Stavros Gigantes, Eirini Grispou, Maria Katsareli, Kimon Fountoulis, Dimitra Oikonomopoulou, Georgia Tounta, Themistoklis Karmiris, Maria-Eleni Karatza, Dimitrios Karakasis, and Zois Mellios
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Foscarnet ,Cellular immunity ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Immunosuppression ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Gastroenterology ,Transplantation ,Letermovir ,Internal medicine ,medicine ,business ,Viral load ,Hemorrhagic cystitis ,medicine.drug - Abstract
Introduction: The preferred method for haploidentical stem cell transplantation (haploSCT) is currently the use of post-transplantation cyclophosphamide (PTCY) since it obviates the need for depletion of T lymphocytes, which is associated with profound immunosuppression. Despite preservation of non-alloreactive donor T cells, reconstitution of pathogen-specific immunity may be delayed even after T cell replete haploSCT. The incidence and clinical sequelae of viral reactivation may thus compromise the outcomes of the procedure. Patients and Methods: The study included 47 patients, who underwent haploSCT with PTCY from 12/2013 until 05/2019 and achieved stable donor engraftment. Median age at transplant was 53 years (range, 19-70). The indications for transplant were acute myeloid (n=19) or lymphoblastic (n=10) leukemia, myelodysplastic syndrome (n=10), myelofibrosis (n=4), chronic myeloid (n=2) or lymphocytic (n=1) leukemia, and T-prolymphocytic leukemia (n=1). Myeloablative conditioning was mainly utilized (n=36), with the exception of certain patients who received reduced-intensity (n=10) or non-myeloablative (n=1) regimens. The graft source was peripheral blood in 29 and bone marrow in 18 cases. Tacrolimus in combination with mycophenolate mofetil was administered for prevention of graft-versus-host disease. Recipient/donor cytomegalovirus (CMV) serostatus was -/- (n=2), -/+ (n= 5), +/- (n=11), or +/+ (n=29). CMV, Epstein-Barr virus (EBV), and human herpesvirus-6 (HHV-6) reactivation was monitored by real-time quantitative PCR (RQ-PCR) in plasma and/or leukocytes weekly for at least 6 months post haploSCT. BK virus (BKV) reactivation was assessed by RQ-PCR in urine and/or blood specimens in cases with symptoms suggestive of hemorrhagic cystitis (HC). Prophylaxis with letermovir was available in 1 patient only, and preemptive antiviral therapy was the principal modality for the management of CMV infection. Cellular immunity reconstitution was assessed by flow cytometry at 3, 6, and 12 months after transplant. Results: With a median follow-up time of 30 months (range, 2-64), the cumulative incidences (CIN) of relapse and non-relapse mortality (NRM) were 13.4% (95% confidence interval [CI], 5.4-25.1%) and 31.4% (95% CI, 18.3-45.4%) at 2 years, respectively. Disease-free (DFS) and overall survival (OS) were 55.2% (95% CI, 42.3-72.1%) and 61.8% (95% CI, 48.9-78.1%) at 2 years, respectively. The CIN of CMV reactivation (>100 copies/ml) plateaued at 75.6% (95% CI, 60.1-85.7%) at 3 months. CMV infection developed in 34 out of 45 patients who were at risk, whereas recurrent CMV reactivation was observed in 17 patients with a median number of 1.5 episodes (range, 1-6) per patient. The median total duration of antiviral therapy for CMV infection was 27 days (range, 14-199). CMV disease (pneumonia) was documented in 2 patients. The CIN of EBV reactivation (>1,000 copies/ml) was 47.1% (95% CI, 34.2-63.9%) at 12 months. No case of EBV-related post-transplant lymphoproliferative disorder was observed, however preemptive therapy with rituximab was required in 2 patients with rapidly increasing EBV viral load. HHV-6 reactivation (>1,000 copies/ml) was observed in 6 patients (CIN, 10.6% at 6 months; 95% CI, 3.8-21.4%), but only one required therapy with foscarnet due to high viral load (>10,000 copies/ml). The CIN of BKV-related HC reached 27.7% (95% CI, 15.7-40.9%) at 3 months. Cystoscopy for bladder hemostasis was required in 5/13 and nephrostomy in 1/11 patients with HC. Reconstitution of helper T cell immunity was considerably delayed, with median absolute CD4+ cell counts of 83/uL (range, 7-337), 216/uL (range, 80-509), and 236/uL (range, 97-586) at 3, 6 and 12 months, respectively. Recurrent CMV infection was significantly associated with the recovery of CD4+ cells at 3 months (Figure; median CD4+ count of 191/uL versus 62/uL in patients with 1 and 2 or more episodes of CMV reactivation, respectively; p=0.009). Conclusions: HaploSCT with PTCY is associated with substantial rates of viral reactivation (especially CMV and BKV) resulting in the need for prolonged antiviral therapy and considerable morbidity. Strategies to prevent viral infection are strongly warranted in haploidentical stem cell transplantation. The timing and duration of such interventions (like letermovir or adoptive immunotherapy) may be guided by the tempo of immune reconstitution following haploSCT. Figure Disclosures Tsonis: Gilead: Other: Travel Grant; Astellas: Other: Travel Grants; Gilead: Other: Travel Grant; Aenorasis: Other: Travel Grant; Takeda: Other: Travel Grant; Pfizer: Other: Travel Grant; Innovis: Other: Travel Grant.
- Published
- 2019
17. Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset #2
- Author
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Jitka Malčíková, Richard Rosenquist, Panagiotis Panagiotidis, C. Belessi, Tatiana Tzenou, P. F. Di Celle, Karla Plevová, Šárka Pospíšilová, Nicola Cahill, Anthonie Willem Langerak, Larry Mansouri, Nicholas Chiorazzi, Christian H. Geisler, Kostas Stamatopoulos, Lone B. Pedersen, Zadie Davis, Lesley-Ann Sutton, Diego Cortese, David Oscier, Panagiotis Baliakas, Evangelia Stalika, Paolo Ghia, Lydia Scarfò, Andreas Agathangelidis, Frederic Davi, Jonathan C. Strefford, Strefford, Jc, Sutton, La, Baliakas, P, Agathangelidis, A, Malcikova, J, Plevova, K, Scarfo, L, Davis, Z, Stalika, E, Cortese, D, Cahill, N, Pedersen, Lb, di Celle, Pf, Tzenou, T, Geisler, C, Panagiotidis, P, Langerak, Aw, Chiorazzi, N, Pospisilova, S, Oscier, D, Davi, F, Belessi, C, Mansouri, L, Ghia, PAOLO PROSPERO, Stamatopoulos, K, Rosenquist R. P., Ghia is joint last author, and Immunology
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Cancer Research ,Chronic lymphocytic leukemia ,Ubiquitin-Protein Ligases ,Biology ,medicine.disease_cause ,Somatic evolution in cancer ,Polymerase Chain Reaction ,law.invention ,Inhibitor of Apoptosis Proteins ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,law ,medicine ,Biomarkers, Tumor ,Humans ,Receptor, Notch1 ,Survival rate ,Gene ,Polymerase chain reaction ,030304 developmental biology ,0303 health sciences ,Mutation ,Hematology ,DNA, Neoplasm ,Ribonucleoprotein, U2 Small Nuclear ,medicine.disease ,Phosphoproteins ,Prognosis ,Leukemia, Lymphocytic, Chronic, B-Cell ,Baculoviral IAP Repeat-Containing 3 Protein ,Survival Rate ,Leukemia ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,RNA Splicing Factors ,Follow-Up Studies - Abstract
Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B-cell receptors and also exhibiting distinct prognoses. Here, we analyzed the mutation status of NOTCH1, SF3B1 and BIRC3 in three subsets with particularly poor prognosis, that is, subset # 1, # 2 and # 8, aiming to explore links between genetic aberrations and immune signaling. A remarkably higher frequency of SF3B1 mutations was revealed in subset # 2 (44%) versus subset # 1 and # 8 (4.6% and 0%, respectively; P
- Published
- 2013
18. Prognostic Contribution of the New Immunoglobulin (Ig) Biomarkers (Freelite™ and Hevylite™) in Waldenstrom’s Macroglobulinemia (WM)
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Efstathios Koulieris, Maria K. Angelopoulou, Dimitrios Maltezas, A. Efthymiou, E. Terpos, Christina Kalpadakis, K. Bitsanis, Ph. Beris, V. Bartzis, E Kastritis, T.P. Vassilakopoulos, N. Kafassi, M. Gavriatopoulou, S. Harding, Tatiana Tzenou, Meletios-Athanassios Dimopoulos, P. Panayiotidis, M.-C. Kyrtsonis, Gerasimos Pangalis, and A. R. Bradwell
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medicine.medical_specialty ,Heavy chain ,General Computer Science ,biology ,business.industry ,Time to first treatment ,Macroglobulinemia ,Immunoglobulin light chain ,Gastroenterology ,Serum free ,Internal medicine ,biology.protein ,medicine ,Antibody ,business ,Kappa - Abstract
Clinical utility of serum free light chains (sFLC) and heavy chain (HLC) IgM were assessed, using Freelite and Hevylite assays in 70 WM patients. The result showed that median involved (i) sFLC -kappa and -lambda were 45.6 and 78.3mg/ L respectively; median sFLC (kappa+lambda) was 67.4 mg/ L. While, median FLCR (involved/uninvolved FLC ratios) were 2.7 and 6.9 in ikappa- and ilambda -restricted patients respectively. Moreover, increased isFLC, sFLC (kappa+lambda) and FLCR were correlated significantly with shorter time to first treatment (TFT) and adverse survival (OVS). Median iIgM-kappa and iIgM -lambda were 25.4 and 34.8g/L respectively; median HLCR (involved/uninvolved HLC ratios) were 185.5 and 101.9 in kappa- and lambda- restricted patients respectively. In addition, the increased iHLC and HLCR correlated significantly with shorter TFT. Hence, sFLC and HLC measurements appeared to be both prognostic in WM.
- Published
- 2012
19. Re-evaluation of prognostic markers including staging, serum free light chains or their ratio and serum lactate dehydrogenase in multiple myeloma patients receiving novel agents
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Theodoros P. Vassilakopoulos, Maria K. Angelopoulou, Konstantinos Anargyrou, Marie-Christine Kyrtsonis, Aikaterini Stefanoudaki, Dimitrios Maltezas, Efstathios Koulieris, Anastasia Pouli, Panagiotis Repousis, Sossana Delimpasi, Gerassimos A. Pangalis, Meletios A. Dimopoulos, Evridiki Michalis, Tatiana Tzenou, Sotiris Sachanas, Irene Katodritou, Evangelos Terpos, Panayiotis Panayiotidis, Maria Dimou, and Maria Gavriatopoulou
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Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Gastroenterology ,Surgery ,Transplantation ,Thalidomide ,chemistry.chemical_compound ,Autologous stem-cell transplantation ,Oncology ,chemistry ,Lactate dehydrogenase ,Internal medicine ,Medicine ,Stage (cooking) ,business ,Survival analysis ,Multiple myeloma ,Lenalidomide ,medicine.drug - Abstract
International Staging System (ISS), serum free light chain ratio (sFLCR) and lactate dehydrogenase (LDH) are well known, easily assessed independent prognostic indicators of outcome in multiple myeloma (MM). The purpose of the study was to re-examine the prognostic contribution of these variables in a multicenter setting with special attention to MM patients treated with autologous stem cell transplantation (ASCT) or novel agents (NA). Three hundred and five symptomatic newly diagnosed MM patients were retrospectively studied. Twenty-seven per cent, 32% and 41% were in ISS stages 1, 2, and 3, respectively. Fifty-six per cent of them presented kappa light chain monoclonality; median sFLCR was 27.04 (0.37–1.9 × 105) and 47.97 (0.26–2.3 × 107) for kappa patients and lambda patients, respectively; patients with sFLCR above median constituted the high sFLCR group. Thirty-one per cent of patients had increased LDH. As first line treatment, 55.7% received conventional treatment and 44.3% NA. After induction, 24% underwent ASCT, whereas 76% received NA at any line, either bortezomib (82.5%), thalidomide (48%) or lenalidomide (27%). When the 305 patients were analyzed together, staging, high sFLCR and abnormal LDH were predictive of survival. The same was true for patients that never received NA, whereas neither high sFLCR nor abnormal LDH constituted adverse factors in patients that received NA frontline. In the last group of patients, no difference was observed between ISS stages 2 and 3. The median 5-year survival of patients that never received NA versus those who did frontline was 29% vs 47%, 7% vs 52% and 24% vs 40% in patients with abnormal LDH, high sFLCR and ISS stage 3, respectively (p = 0.03, p
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- 2012
20. CD138 Expression Helps Distinguishing Waldenström's Macroglobulinemia (WM) From Splenic Marginal Zone Lymphoma (SMZL)
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Dimitrios Maltezas, Maria K. Angelopoulou, Penelope Korkolopoulou, Maria Dimou, Panayiotis Panayiotidis, Marie-Christine Kyrtsonis, George Georgiou, Christina Kalpadakis, Efstathios Koulieris, Gerassimos A. Pangalis, Theodoros P. Vassilakopoulos, Efstratios Patsouris, Panagiotis Tsaftaridis, Tatiana Tzenou, Vassilis Salpeas, Vassiliki Bartzi, and Georgia Levidou
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Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Splenic Neoplasm ,Context (language use) ,Immunophenotyping ,Diagnosis, Differential ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Splenic marginal zone lymphoma ,Aged ,business.industry ,Splenic Neoplasms ,Macroglobulinemia ,Waldenstrom macroglobulinemia ,Lymphoma, B-Cell, Marginal Zone ,Hematology ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Female ,Syndecan-1 ,Bone marrow ,Waldenstrom Macroglobulinemia ,Differential diagnosis ,business - Abstract
The distinction between WM and SMZL may be difficult since both entities share overlapping clinical, immunophenotypic, and histopathologic characteristics. In this context we evaluated whether CD138 expression could be added in the armamentarium of tools used to differentiate these entities. Sixty-nine patients were studied, 47 WM and 22 SMZL. Paraffin-embedded sections of bone marrow biopsies were quantitatively and qualitatively evaluated for CD138 expression. Sixty percent of WM cases expressed CD138 in contrast to 18% of SMZL patients. Intermediate/high intensity of CD138 expression was observed in 47% of WM while it was low in all SMZL patients. Differences between WM and SMZL regarding the intensity and the percentage of CD138 positive cells were both significant (P = .0008 and, .00021 respectively). Moreover, CD138 expression was related to serum IgM levels in WM patients (P = .0006). In conclusion, CD138 expression may constitute an additional aid in the distinction between WM and SMZL.
- Published
- 2011
21. Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma
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Maria N. Dimopoulou, Marie-Christine Kyrtsonis, Theodoros P. Vassilakopoulos, Evangelia M. Dimitriadou, Zacharoula Galanis, Gerassimos A. Pangalis, Marina P. Siakantaris, Nicoletta Kafasi, Tatiana Tzenou, Argiroula Papadogiannis, Maria K. Angelopoulou, Christina Kalpadakis, Maria Dimou, Styliani I. Kokoris, Elias Kyriakou, Panayiotis Panayiotidis, and Sotirios Sachanas
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Male ,medicine.medical_specialty ,Pathology ,Immunoglobulin light chain ,Gastroenterology ,Immunoglobulin kappa-Chains ,chemistry.chemical_compound ,Immunoglobulin lambda-Chains ,Bone Marrow ,Serum free ,Lactate dehydrogenase ,Internal medicine ,medicine ,Humans ,In patient ,Multiple myeloma ,Aged ,Hematology ,L-Lactate Dehydrogenase ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Elevated serum creatinine ,chemistry ,Creatinine ,Monoclonal ,Female ,Immunoglobulin Light Chains ,Multiple Myeloma ,business ,Biomarkers - Abstract
The prognostic value of baseline serum free light chain ratio (sFLCR) was investigated in 94 multiple myeloma (MM) patients. sFLCR was calculated as kappa/lambda or lambda/kappa, depending on the patients' dominating monoclonal light chain. Median baseline sFLCR was 3.57 in kappa-MM patients, 45.09 in lambda-MM. 'High' sFLCR (or = the observed median value for kappa- and lambda-MM respectively) correlated with elevated serum creatinine and lactate dehydrogenase, extensive marrow infiltration and light chain type MM. The 5-year disease-specific survival was 82% and 30% in patients with sFLCR lower than and equal or greater than the median, respectively (P = 0.0001). sFLCR was an independent prognostic factor.
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- 2007
22. Validation of Frailty Assessment in Multiple Myeloma (MM) Patients
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Maria Dimou, Eftychia Nikolaou, Dimitrios Maltezas, Theodoros Iliakis, Sotiria Kotsanti, Paraskevi Papaioannou, Efstathios Koulieris, Marie-Christine Kyrtsonis, Tatiana Tzenou, Panayiota Petsa, Aikaterini Bitsani, and Panayiotis Panayiotidis
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Hematology ,medicine.disease ,Frailty assessment ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,030212 general & internal medicine ,business ,030217 neurology & neurosurgery ,Multiple myeloma - Published
- 2017
23. Assessment of bortezomib induced peripheral neuropathy in multiple myeloma by the reduced Total Neuropathy Score
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Chrysothea K Zaroulis, Ilias Pessach, Tatiana Tzenou, Efstathios Koulieris, Dimitris Maltezas, Eleni Koutra, Konstantinos Kilindireas, Marie-Christine Kyrtsonis, Gerasimos Pangalis, Konstantinos Chairopoulos, and Sotirios Sachanas
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents ,Bortezomib ,Risk Factors ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,In patient ,Multiple myeloma ,Aged ,Aged, 80 and over ,Neurologic Examination ,business.industry ,Follow up studies ,Peripheral Nervous System Diseases ,Refractory Multiple Myeloma ,Hematology ,Middle Aged ,medicine.disease ,Boronic Acids ,Surgery ,Peripheral neuropathy ,Pyrazines ,Female ,business ,Multiple Myeloma ,medicine.drug ,Follow-Up Studies - Abstract
We evaluated bortezomib induced peripheral neuropathy (BIPN) characteristics in an attempt to better clarify the type, grade, duration and reversibility of neuropathy as well as investigate possible peripheral neuropathy (PN) risk factors and detect the best way to manage it. We calculated the grading of neuropathy using the Total Neuropathy Score reduced version (TNSr) in a series of 51 patients with relapsed/refractory multiple myeloma treated with bortezomib. Seventy percent developed clinical PN. BIPN, although manageable, is frequently underestimated in patients treated with bortezomib intravenously. Continuous follow-up and management of PN are needed to avoid quality of life impairment.
- Published
- 2014
24. Clonotypic Analysis of Immunoglobulin Heavy Chain Sequences in Patients with Waldenström’s Macroglobulinemia: Correlation with MYD88 L265P Somatic Mutation Status, Clinical Features, and Outcome
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Tatiana Tzenou, Loizos Petrikkos, Marie-Christine Kyrtsonis, Anna Efthymiou, Maria Roumelioti, George Georgiou, and Panayiotis Panayiotidis
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Adult ,Male ,Article Subject ,DNA Mutational Analysis ,Somatic hypermutation ,lcsh:Medicine ,Locus (genetics) ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Germline mutation ,medicine ,Humans ,Aged ,Aged, 80 and over ,Genetics ,Base Sequence ,General Immunology and Microbiology ,lcsh:R ,Electrophoresis, Capillary ,Macroglobulinemia ,Waldenstrom macroglobulinemia ,General Medicine ,Middle Aged ,medicine.disease ,Clone Cells ,Treatment Outcome ,Amino Acid Substitution ,Mutation ,Myeloid Differentiation Factor 88 ,Immunology ,Monoclonal ,Immunoglobulin heavy chain ,Female ,Waldenstrom Macroglobulinemia ,Immunoglobulin Heavy Chains ,IGHV@ ,Research Article - Abstract
We performedIGHclonotypic sequence analysis in WM in order to determine whether a preferentialIGHgene rearrangement was observed and to assessIGHVmutational status in blood and/or bone marrow samples from 36 WM patients. In addition we investigated the presence ofMYD88L265P somatic mutation. AfterIGHVDJ locus amplification, monoclonal VDJ rearranged fragments were sequenced and analyzed.MYD88L265P mutation was detected by AS-PCR. The most frequent family usage wasIGHV3(74%);IGHV3-23andIGHV3-74segments were used in 26% and 17%, respectively. Somatic hypermutation was seen in 91% of cases.MYD88L265P mutation was found in 65,5% of patients and absent in the 3 unmutated. These findings did not correlate with clinical findings and outcome. Conclusion.IGH genes’repertoire differed in WM from those observed in other B-cell disorders with a recurrentIGHV3-23andIGHV3-74usage; monoclonalIGHVwas mutated in most cases, and a high but not omnipresent prevalence ofMYD88L265P mutation was observed. In addition, the identification of 3 patients with unmutatedIGHVgene segments, negative for theMYD88L265P mutation, could support the hypothesis that an extra-germinal B-cell may represent the originating malignant cell in this minority of WM patients.
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- 2014
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25. Serum Soluble TACI, a BLyS Receptor, Is a Powerful Prognostic Marker of Outcome in Chronic Lymphocytic Leukemia
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Maria K. Angelopoulou, Eftychia Nikolaou, Dimitrios Maltezas, Katerina Sarris, Maria Dimou, Petros P. Sfikakis, Nora Viniou, Mariana P. Siakandaris, Marie-Christine Kyrtsonis, Efstathios Koulieris, Vassiliki Bartzis, Tatiana Tzenou, Gerassimos A. Pangalis, Christina Kalpadakis, Panayiotis Panayiotidis, and Sotirios Sachanas
- Subjects
Adult ,Male ,Article Subject ,Anemia ,Chronic lymphocytic leukemia ,Transmembrane Activator and CAML Interactor Protein ,lcsh:Medicine ,Kaplan-Meier Estimate ,Immunoglobulin light chain ,General Biochemistry, Genetics and Molecular Biology ,Receptors, Tumor Necrosis Factor ,Disease activity ,medicine ,Biomarkers, Tumor ,Humans ,B-cell activating factor ,Receptor ,Aged ,Aged, 80 and over ,General Immunology and Microbiology ,business.industry ,Time to first treatment ,lcsh:R ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Leukemia, Lymphocytic, Chronic, B-Cell ,Immunology ,Female ,business ,Research Article - Abstract
BLyS is involved in CLL biology and its low soluble serum levels related to a shorter time to first treatment (TFT). TACI is a BLyS receptor and can be shed from cells’ surface and circulate in soluble form (sTACI). We investigated the impact of serum BLyS and sTACI levels at diagnosis in CLL patients and their relationship with disease parameters and patients’ outcome. Serum BLyS was determined in 73 patients, while sTACI in 60. Frozen sera drawn at diagnosis were tested by ELISA. sTACI concentrations correlated with BLyS (P=-0.000021), b2-microglobulin (P=0.005), anemia (P=-0.03), thrombocytopenia (P=0.04), Binet stage (P=0.02), and free light chains ratio (P=0.0003). Soluble BLyS levels below median and sTACI values above median were related to shorter TFT (P=0.0003and 0.007). During a ten-year followup, sTACI levels, but not BLyS, correlated with survival (P=0.048). In conclusion, we confirmed the prognostic significance of soluble BLyS levels with regard to TFT in CLL patients, and, more importantly, we showed for the first time that sTACI is a powerful prognostic marker, related to parameters of disease activity and staging and, more importantly, to TFT and OS.
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- 2014
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26. Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia
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Dimitrios Maltezas, Panayiotis Panayiotidis, Tatiana Tzenou, Katerina Bitsani, Katerina Sarris, Efstathios Koulieris, Marina P. Siakantaris, Flora N. Kontopidou, Anna Efthymiou, Theodoros P. Vassilakopoulos, Marie-Christine Kyrtsonis, Gerasimos Pangalis, Panagiotis Tsaftaridis, Eftychia Nikolaou, Sotirios Sachanas, Nikolitsa Kafasi, Maria Dimou, Stephen E. Harding, Maria K. Angelopoulou, and Vassiliki Bartzis
- Subjects
medicine.medical_specialty ,Pathology ,biology ,Article Subject ,business.industry ,Chronic lymphocytic leukemia ,Time to treatment ,Serum albumin ,Hematology ,Immunoglobulin light chain ,medicine.disease ,Gastroenterology ,Serum free ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Overall survival ,biology.protein ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Stage (cooking) ,business ,Research Article - Abstract
Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients.Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients’ series.Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients’ followup was 32 months (range 4–228).Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P=0.0005andP=0.000003, resp.) and overall survival (P=0.05andP=0.003, resp.). They also correlated withβ2-microglobulin (P=0.009andP=0.03, resp.), serum albumin (P=0.009for summated sFLC), hemoglobin (P<0.001), abnormal LDH (P=0.037andP=0.001, resp.), Binet stage (P<0.05) and with the presence of beta symptoms (P=0.004for summated sFLC).Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters.
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- 2013
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27. Incidence, clinical features, laboratory findings and outcome of patients with multiple myeloma presenting with extramedullary relapse
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Vassiliki Bartzis, Dimitris Maltezas, Elektra Dimitrakoloulou, Maria Kotsopoulou, Efstathios Koulieris, Gerasimos Pangalis, Maria K. Angelopoulou, Tatiana Tzenou, Katerina Megalakaki, Panagiotis Panayotidis, Marie-Christine Kyrtsonis, Xenofon Papanikolaou, and Panagiotis Repousis
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Constitutional symptoms ,Gastroenterology ,Recurrence ,Internal medicine ,Overall survival ,Medicine ,Humans ,In patient ,Survival analysis ,Multiple myeloma ,Aged ,business.industry ,Bortezomib ,Incidence (epidemiology) ,Incidence ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,Surgery ,Treatment Outcome ,Oncology ,Monoclonal ,Female ,business ,Multiple Myeloma ,medicine.drug ,Plasmacytoma - Abstract
Extramedullary plasmacytomas constitute a rare and not well studied subset of multiple myeloma (MM) relapses. We report the incidence, clinical-laboratory features and outcome of patients with MM and extramedullary relapse (ExMeR). A total of 303 patients with symptomatic MM were recorded in a 13-year period in two institutions. Twenty-eight cases of ExMeR (9%) were recorded. There was an increased frequency of elevated lactate dehydrogenase (LDH) (p = 0.026), bone plasmacytomas (p = 0.001) and fractures (p = 0.002) at diagnosis, in patients with ExMeR compared to the others. ExMeR was associated with an ominous outcome, high LDH, constitutional symptoms and a statistically significant decrease of monoclonal paraprotein compared to levels at diagnosis (p = 0.009). Prior treatment with bortezomib was associated with a decreased hazard of ExMeR (p = 0.041). Overall survival (OS) was decreased in patients with ExMeR compared to the others (38 vs. 59 months, p = 0.006). Patients with MM with ExMeR have a lower OS and their clinical and laboratory features differ from those without.
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- 2012
28. Chapter 8 The Contribution of Prognostic Factors to the Better Management of Multiple Myeloma Patients
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Tatiana Tzenou, Katerina Bitsani, Marie-Christine Kyrtsonis, Dimitrios Maltezas, Anna Efthymiou, Ilias Pessach, Vassiliki Bartzis, Panayiotis Panayiotidis, and Efstathios Koulieris
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Oncology ,medicine.medical_specialty ,business.industry ,Disease mechanisms ,Disease ,medicine.disease ,Pathogenesis ,medicine.anatomical_structure ,Internal medicine ,Etiology ,Medicine ,Variable disease course ,Bone marrow ,business ,Infiltration (medical) ,Multiple myeloma - Abstract
Multiple myeloma (MM) is an heterogeneous plasma cell disorder of unknown etiology, with a wide range of clinical manifestations and a highly variable disease course. Survival varies from a few months to more than ten years. The disease is characterized by bone marrow (BM) infiltration by malignant plasma cells usually secreting a serum or urine monoclonal immunoglobulin (Ig) component. Progress has been made in the understanding of its pathogenesis including knowledge of BM microenvironment and of cellular and genetic factors implicated in disease mechanisms that are not uniform in all patients, thus partly explaining disease variability. Furthermore, based on these, new very performing biology-based treatment modalities have been developed and are either already available for patients or under evaluation.
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- 2012
29. Re-evaluation of prognostic markers including staging, serum free light chains or their ratio and serum lactate dehydrogenase in multiple myeloma patients receiving novel agents
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Dimitrios, Maltezas, Meletios A, Dimopoulos, Irene, Katodritou, Panagiotis, Repousis, Anastasia, Pouli, Evangelos, Terpos, Panayiotis, Panayiotidis, Sossana, Delimpasi, Evridiki, Michalis, Konstantinos, Anargyrou, Maria, Gavriatopoulou, Aikaterini, Stefanoudaki, Tatiana, Tzenou, Efstathios, Koulieris, Sotiris, Sachanas, Maria, Dimou, Theodoros P, Vassilakopoulos, Maria K, Angelopoulou, Gerassimos A, Pangalis, and Marie-Christine, Kyrtsonis
- Subjects
L-Lactate Dehydrogenase ,Biomarkers, Tumor ,Hematopoietic Stem Cell Transplantation ,Humans ,Multiple Myeloma ,Prognosis ,Survival Analysis ,Transplantation, Autologous ,Disease-Free Survival ,Neoplasm Staging - Abstract
International Staging System (ISS), serum free light chain ratio (sFLCR) and lactate dehydrogenase (LDH) are well known, easily assessed independent prognostic indicators of outcome in multiple myeloma (MM). The purpose of the study was to re-examine the prognostic contribution of these variables in a multicenter setting with special attention to MM patients treated with autologous stem cell transplantation (ASCT) or novel agents (NA). Three hundred and five symptomatic newly diagnosed MM patients were retrospectively studied. Twenty-seven per cent, 32% and 41% were in ISS stages 1, 2, and 3, respectively. Fifty-six per cent of them presented kappa light chain monoclonality; median sFLCR was 27.04 (0.37-1.9 × 10(5) ) and 47.97 (0.26-2.3 × 10(7) ) for kappa patients and lambda patients, respectively; patients with sFLCR above median constituted the high sFLCR group. Thirty-one per cent of patients had increased LDH. As first line treatment, 55.7% received conventional treatment and 44.3% NA. After induction, 24% underwent ASCT, whereas 76% received NA at any line, either bortezomib (82.5%), thalidomide (48%) or lenalidomide (27%). When the 305 patients were analyzed together, staging, high sFLCR and abnormal LDH were predictive of survival. The same was true for patients that never received NA, whereas neither high sFLCR nor abnormal LDH constituted adverse factors in patients that received NA frontline. In the last group of patients, no difference was observed between ISS stages 2 and 3. The median 5-year survival of patients that never received NA versus those who did frontline was 29% vs 47%, 7% vs 52% and 24% vs 40% in patients with abnormal LDH, high sFLCR and ISS stage 3, respectively (p = 0.03, p 0.00001 and p = 0.035). In conclusion, patients gaining the most from NA are those with an aggressive disease as reflected by advanced stage, abnormal LDH and high sFLCR. In addition, the adverse impact of these three variables is obscured by NA.
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- 2012
30. Study of MGUS-Series: Disease Evolution, Coexistant Disorders and Other Clinical Observations
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Panayiotis Panayiotidis, Aikaterini Bitsani, Sotiria Kotsanti, Nikolaou Eftychia, Dimitrios Maltezas, Theodoros Iliakis, Paraskevi Papaioannou, Marie-Christine Kyrtsonis, Tatiana Tzenou, Panagiota Petsa, and Maria Dimou
- Subjects
medicine.medical_specialty ,education.field_of_study ,Pathology ,business.industry ,Myelodysplastic syndromes ,Thyroid disease ,Immunology ,Population ,Waldenstrom macroglobulinemia ,Cell Biology ,Hematology ,medicine.disease ,Malignancy ,Biochemistry ,Asymptomatic ,Gastroenterology ,hemic and lymphatic diseases ,Internal medicine ,medicine ,medicine.symptom ,business ,education ,Monoclonal gammopathy of undetermined significance ,Multiple myeloma - Abstract
Introduction: Monoclonal Gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder occurring mainly in the elderly population. Its evolution, association with various diseases and behavior is an interesting study field in an attempt to understand its pathogenesis and disease course. Aim: To study the grade of coexistence of non-malignant and malignant diseases along with disease evolution and behavior in patients with MGUS, diagnosed in a single center. Patients and methods:We studied 138 MGUS-patients that were diagnosed in our center and then followed up to a median of 36 months (6months - 22 years). Median age was 66 years (27-92 years). 57% were of female sex. Monoclonal heavy chain was IgG in 76%, IgA in 14% and IgM in 10% of the patients while 63% presented k-chain clonality. Non-malignant and malignant preexisting diseases were documented at the time point of MGUS-Diagnosis. Patients with B-NHL expressing monoclonal Protein were not classified as MGUS since malignant B-Lymphocytes can be responsible for its production. Results: 10.9% of the patients presented solid tumors. The most common malignancy was Prostate-Cancer in 8.5% of the male patients followed by Thyroid-Cancer which was present in 2.2% of the whole patient group.Hematological malignancies were existent in 10.9% of the patients. 4.3% presented myeloproliferative neoplasms while myelodysplastic syndromes were represented in 5% of the patients.18.1% of the patients presented with diverse benign tumors, 8% had been diagnosed with Diabetes Mellitus while 32.6% presented cardiovascular disease, mainly hypertension (23.2%). Hyperlipidemia was present in 8.7%. Finally 18.1% of the patients presented non-malignant thyroid disease, mainly hypothyroidism (10.9%) which is increased compared to the general population.17 MGUS-Patients (12%) presented disease evolution. 3 Patients evolved directly to multiple myeloma while 3 more evolved initially to smoldering myeloma (SMM) before developing overt myeloma. 8 patients evolved to SMM without any further progression. 2 patients with IgM-MGUS presented Waldenström's maroglobulinemia in the follow up while one patient developed a B-NHL. We performed a statistical analysis, where only abnormal serum free light chain ratio (sFLCR) was found to have a prognostic impact on MGUS-progression (p=0.03).Within this group of evolving MGUS-patients two of them presented a very remarkable course. The first one was diagnosed with MGUS while she was in remission after Hodgkin's Lymphoma. She evolved then to SMM confirmed by bone marrow biopsy with more than 10% plasma cell infiltration by immunohistochemistry. After being stable for several months, monoclonal protein was no longer detectable and plasma cells in the bone marrow were normal without any treatment. The second patient was initially diagnosed with MGUS with a high sFLCR of 60. She then evolved to SMM with further sFLCR-increase up to 100 but remained without treatment according to the guidelines at that time. Four years later she developed anemia and the final diagnosis was B-NHL. Conclusion: In our study group MGUS was associated with numerous malignant and non-malignant disorders. Hypothyroidism was a common finding, increased compared to the general population. MGUS-evolution was also observed however disease course was unexpected in some patients showing the heterogeneity of the disease. sFLCR was confirmed as a prognostic factor. Further study is necessary to investigate any possible implication of the above findings in the disease pathogenesis and course. Disclosures Kyrtsonis: Genesis: Honoraria; Millenium: Research Funding; Lilly: Research Funding; Amgen: Research Funding.
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- 2015
31. CLL with Mutated IGHV4-34 Antigen Receptors Is Clinically Heterogeneous: Antigen Receptor Stereotypy Makes the Difference
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Alba Navarro, Panagiotis Baliakas, Lone Bredo Pedersen, Richard Rosenquist, Stephan Stilgenbauer, Véronique Giudicelli, Yorick Sandberg, Elias Campo, Tatiana Tzenou, Gunnar Juliusson, Monica Facco, Andrey Sudarikov, Niki Stavroyianni, Teodora Karan-Djurasevic, Nikos Darzentas, Charles C. Chu, Eva Minga, Karla Plevová, Frederic Davi, Maria Chatzouli, Chrysoula Belessi, Livio Trentin, Paolo Ghia, Marie-Paule Lefranc, Davide Rossi, Xiao J. Yan, Šárka Pospíšilová, Diane F. Jelinek, Carsten Utoft Niemann, Jasmin Bahlo, Karin E. Smedby, Myriam Boudjogra, Mark Catherwood, Larry Mansouri, Darko Antic, Silvio Veronese, Lydia Scarfò, Andreas Agathangelidis, Marco Montillo, Zadie Davis, Anastasia Hadzidimitriou, Michael Hallek, Tait D. Shanafelt, Hartmut Döhner, Kostas Stamatopoulos, Achilles Anagnostopoulos, David Oscier, Nicholas Chiorazzi, Gianluca Gaidano, Eugen Tausch, Fie Juhl Vojdeman, Panagiotis Panagiotidis, Dirk Kienle, Aliki Xochelli, Lesley-Ann Sutton, and Anton W. Langerak
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0303 health sciences ,medicine.medical_specialty ,Mutation ,Hematology ,biology ,Immunology ,Cell Biology ,CD38 ,medicine.disease_cause ,Biochemistry ,3. Good health ,03 medical and health sciences ,Stereotypy (non-human) ,0302 clinical medicine ,Antigen ,Immunoglobulin M ,Internal medicine ,biology.protein ,medicine ,Gene ,Antigen receptors ,030304 developmental biology ,030215 immunology - Abstract
The IGHV4-34 gene is very frequent (~10%) in the B cell receptor immunoglobulin (BcR IG) gene repertoire of chronic lymphocytic leukemia (CLL). Over 30% of IGHV4-34 CLL cases can be assigned to different subsets with stereotyped BcR IG. The largest is subset #4 which represents ~1% of all CLL and ~10% of IGHV4-34 CLL and is considered a prototype for indolent disease. The BcR IG of a great majority (~85%) of IGHV4-34 CLL cases carry a significant load of somatic hypermutation (SHM), often with distinctive SHM patterns. This holds especially true for stereotyped subsets and is suggestive of particular modes of interactions with the selecting antigen(s). In detail, subsets #4 and #16, both involving IgG-switched cases (IgG-CLL), exhibit the greatest sequence similarity in SHM profiles, whereas they differ in this respect from IgM/D subsets #29 and #201. Prompted by these observations, here we explored the extent that these subset-biased SHM profiles in different IGHV4-34 stereotyped subsets were reflected in distinct demographics, clinical presentation, genomic aberrations and outcomes. Within a multi-institutional series of 20,331 CLL patients, 1790 (8.8%) expressed IGHV4-34 BcR IG. Following established bioinformatics approaches for the identification of BcR IG stereotypy, 573/1790 IGHV4-34 CLL cases (32%) were assigned to stereotyped subsets; of these, 340 cases (19% of all IGHV4-34 CLL and 60% of stereotyped IGHV4-34 cases) belonged to subsets #4, #16, #29 and #201, all concerning IGHV-mutated CLL (M-CLL). Clinicobiological information was available for 275/340 patients: #4, n=150; #16, n=44; #29, n=39; and #201, n=42. Comparisons between subsets revealed no differences in gender and age distribution. Interestingly, however, 36-43% of each subset cases were young for CLL (defined as patients aged ≤55 years), which is higher compared to general CLL cohorts, where young patients generally account for ~25% of cases. In contrast, significant differences were identified between subsets regarding: (i) disease stage at diagnosis, with >90% of IgG subsets #4 and #16 diagnosed at Binet stage A versus 83% in subset #201 and 74% in subset #29 (p=0.029); (ii) CD38 expression, ranging from 1% in subset #4 to 10% in subset #201 (p=0.013); (iii) the distribution of del(13q), peaking at a remarkable 92% in subset #29 versus only 37% in subset #16 (p Disclosures Tausch: Gilead: Other: Travel support. Shanafelt:Glaxo-Smith_Kline: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Polyphenon E Int'l: Research Funding; Hospira: Research Funding; Janssen: Research Funding; Pharmactckucs: Research Funding; Cephalon: Research Funding. Niemann:Gilead: Consultancy; Janssen: Consultancy; Roche: Consultancy; Novartis: Other: Travel grant. Langerak:InVivoScribe: Patents & Royalties: Licensing of IP and Patent on BIOMED-2-based methods for PCR-based Clonality Diagnostics.; DAKO: Patents & Royalties: Licensing of IP and Patent on Split-Signal FISH. Royalties for Dept. of Immunology, Erasmus MC, Rotterdam, NL; Roche: Other: Lab services in the field of MRD diagnostics provided by Dept of Immunology, Erasmus MC (Rotterdam). Hallek:Celgene: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; AbbVie: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Roche: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Boehringher Ingelheim: Honoraria, Other: Speakers Bureau and/or Advisory Boards; Pharmacyclics: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Mundipharma: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Janssen: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding; Gilead: Honoraria, Other: Speakers Bureau and/or Advisory Boards, Research Funding. Ghia:Janssen Pharmaceuticals: Research Funding.
- Published
- 2015
32. Mutation analysis of IgVH genes in splenic marginal zone lymphomas: correlation with clinical characteristics and outcome
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Christina, Kalpadakis, Gerassimos A, Pangalis, Evangelia, Dimitriadou, Maria K, Angelopoulou, Marina P, Siakantaris, Marie-Christine, Kyrtsonis, Maria, Ximeris, Tatiana, Tzenou, Sotirios, Sahanas, Xanthi, Yiakoumis, Eleni A, Papadaki, Panayiotis, Panayiotidis, and Theodoros, Vassilakopoulos
- Subjects
Adult ,Aged, 80 and over ,Male ,Treatment Outcome ,Lymphoma ,Genes, Immunoglobulin Heavy Chain ,Splenic Neoplasms ,Mutation ,Humans ,Female ,Middle Aged ,Aged - Abstract
To determine the immunoglobulin variable heavy chain (IgVH) gene usage and somatic mutation patterns in a series of SMZL patients and to correlate these findings with the clinical features and outcome.IgVH genes were amplified and sequenced from 22 SMZL cases. Clinical and laboratory data of these patients were recorded.A biased usage of IgVH gene was found with overrepresentation of VH3 in 16/22 cases. A total of 13/22 (59%) of cases were found to have mutated IgVH genes, whereas 9/22 (41%) were unmutated. Positive antigen selection process was identified in two cases. Treatment was different between the cases with mutation and those without. No differences in clinical and laboratory characteristics, or survival were found between the mutated and unmutated cases.SMZL are characterized by marked molecular heterogeneity. A biased usage of certain sequences suggests antigen selection. Prognostic significance of mutational status was not confirmed in this study. However further studies are needed in order to confirm these results.
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- 2009
33. Staging systems and prognostic factors as a guide to therapeutic decisions in multiple myeloma
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Dimitrios Maltezas, Tatiana Tzenou, Marie-Christine Kyrtsonis, Arthur R. Bradwell, and Efstathios Koulieris
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Oncology ,medicine.medical_specialty ,Performance status ,L-Lactate Dehydrogenase ,business.industry ,Renal function ,Cancer ,Hematology ,medicine.disease ,Kidney ,Disease-Free Survival ,Surgery ,Survival Rate ,Risk groups ,Serum free ,Internal medicine ,medicine ,Humans ,Variable disease course ,business ,Multiple Myeloma ,Survival rate ,Multiple myeloma ,Serum Albumin ,Neoplasm Staging - Abstract
Multiple myeloma (MM) patients have a highly variable disease course and survival varies from a few months to more than 10 years. Numerous prognostic factors have been identified, including age, performance status (PS), serum albumin, beta2-microglobulin (beta2M), lactate dehydrogenase (LDH), renal function, genetic factors, and serum free light chains (sFLCs) or their ratio (sFLCR). Several models have been built to separate patients into various risk groups with different outcomes. Staging systems need to be simple, accurate, and readily available in order to effectively guide treatment decisions now that effective treatments exist that prolong survival. The International Staging System (ISS) is currently in use; it is highly prognostic but presents some limitations. We suggest that the ISS prognostic potential could be improved with the addition of sFLCR and eventually LDH.
- Published
- 2009
34. Non-gastric extra-nodal marginal zone lymphomas--a single centre experience on 76 patients
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Eleni Papadaki, Panagiota Roussou, Tatiana Tzenou, Theodoros P. Vassilakopoulos, Xanthi Yiakoumis, Maria K. Angelopoulou, Sotirios Sahanas, Flora N. Kontopidou, Marina P. Siakantaris, Christina Kalpadakis, Dimitra Anagnostou, Evangelos Patsouris, Panayiotis Panayiotidis, Evangelia M. Dimitriadou, Gerassimos A. Pangalis, Panagia Bobotsis, Penelope Korkolopoulou, and Maria-Christina Kyrtsonis
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents ,Gastroenterology ,Young Adult ,Internal medicine ,medicine ,Humans ,Progression-free survival ,Lymph node ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Lung ,Chlorambucil ,business.industry ,Remission Induction ,Hematology ,Lymphoma, B-Cell, Marginal Zone ,Middle Aged ,medicine.disease ,Marginal zone ,Survival Analysis ,Lymphoma ,Surgery ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,Female ,Bone marrow ,business ,medicine.drug - Abstract
In the present study, we assessed the clinical and pathological data of 76 patients with the diagnosis of non-gastric extranodal marginal zone B-cell lymphoma. The most commonly affected sites were salivary glands, skin, ocular adnexa, lung, intestine and Waldeyer's ring. Ann Arbor stage I disease was present in 39 patients (51%), stage II in 10 (13%) and stage IV in 27 (36%). In 17 cases (21%), the lymphoma presented at multiple mucosal sites. Lymph node and bone marrow involvement were present in 21% and 16%, respectively. Most cases were in the low or low-intermediate risk group. Treatment was heterogeneous and included chlorambucil in 59% either alone or in combination with other agents. Complete and partial remission was achieved in 79% and 7%, respectively, with an overall response rate of 86%. The 5- and 10-year overall survival and cause-specific survival rates were 94%, 82% and 95%, 91%, respectively. The 5- and 10-year progression free survival was 56% and 41%, respectively. The only feature associated with inferior outcome was disease localisation to the lung.
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- 2008
35. Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib
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Gerassimos A. Pangalis, Theodoros P. Vassilakopoulos, Anastasia Pouli, Meletios A. Dimopoulos, Evangelos Terpos, Tatiana Tzenou, Dimitrios Christoulas, Evangelia M. Dimitriadou, Christina Kalpadakis, Konstantinos Tsionos, Maria K. Angelopoulou, Panayiotis Panayiotidis, Sotirios Sachanas, Marie-Christine Kyrtsonis, Stavroula Masouridis, and Konstantinos Anargyrou
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Adult ,Male ,medicine.medical_specialty ,Antineoplastic Agents ,Gastroenterology ,Angiopoietin ,Neovascularization ,Angiopoietin-2 ,Bortezomib ,Bone Marrow ,Immunopathology ,Internal medicine ,medicine ,Angiopoietin-1 ,Biomarkers, Tumor ,Humans ,Protease Inhibitors ,cardiovascular diseases ,Multiple myeloma ,Aged ,Aged, 80 and over ,Salvage Therapy ,Hematology ,integumentary system ,Neovascularization, Pathologic ,business.industry ,Middle Aged ,medicine.disease ,Boronic Acids ,Receptor, TIE-2 ,Pathophysiology ,Neoplasm Proteins ,Endocrinology ,Treatment Outcome ,Drug Resistance, Neoplasm ,Pyrazines ,embryonic structures ,cardiovascular system ,Proteasome inhibitor ,Female ,medicine.symptom ,business ,Multiple Myeloma ,circulatory and respiratory physiology ,medicine.drug - Abstract
Neoangiogenesis is involved in the pathophysiology of multiple myeloma and angiopoietins possibly contribute to myeloma-induced neovascularization. Bortezomib's antineoplastic potential includes an anti-angiogenic effect. We determined serum levels of angiopoietin-1 and angiopoietin-2 with ELISA pre- and post-bortezomib administration in 35 patients with relapsed/refractory multiple myeloma. Pre-bortezomib, serum angiopoietin-1 levels did not differ in patients and in healthy individuals, while serum angiopoietin-2 levels were elevated. Corresponding serum angiopoietin-1/angiopoietin-2 ratio was reduced in patients compared with controls. After treatment, serum angiopoietin-1 levels increased, while serum angiopoietin-2 levels decreased, therefore the angiopoietin-1/angiopoietin-2 ratio increased and normalized. This increase was significant in patients who responded to treatment. In conclusion, angiopoietin-1/angiopoietin-2 ratio normalization reflected response to bortezomib.
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- 2008
36. Serum levels of soluble syndecan-1 in Hodgkin's lymphoma
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Theodoros P, Vassilakopoulos, Marie-Christine, Kyrtsonis, Argiroula, Papadogiannis, Gianpaolo, Nadali, Maria K, Angelopoulou, Tatiana, Tzenou, Maria N, Dimopoulou, Marina P, Siakantaris, Flora N, Kontopidou, Christina, Kalpadakis, Styliani I, Kokoris, Evangelia M, Dimitriadou, Panayiotis, Tsaftaridis, Giovanni, Pizzolo, and Gerassimos A, Pangalis
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Adult ,Male ,Membrane Glycoproteins ,Syndecans ,Adolescent ,Humans ,Female ,Proteoglycans ,Syndecan-1 ,Middle Aged ,Hodgkin Disease ,Disease-Free Survival ,Aged - Abstract
Syndecan-1 (CD138) is expressed by the Hodgkin-Reed-Sternberg (HRS) cells of classic Hodgkin's lymphoma (cHL), but not in nodular lymphocyte-predominant HL. Syndecan-1 may be involved in the interaction between HRS cells and the cellular and stromal microenvironment typical of nodular sclerosing HL.Serum levels of soluble syndecan-1 were determined by ELISA in 66 patients with HL and 14 age- and sex-matched healthy individuals.The levels of syndecan-1 were higher in HL patients than controls (100.2 +/- 35.9 ng/ml vs. 67.9 +/- 24.5 ng/ml, p0.001). They marginally correlated with advanced age (p = 0.06), male gender (p = 0.07) and consequently high IPS (p = 0.01), but did not correlate with markers of tumor burden and prognosis, including serum interleukin-10 and soluble CD30. At 6 years, failure-free survival was 70 +/- 9% vs. 50 +/- 11% (p = 0.32) for patients with serum soluble syndecan-1 levels above or below the observed median value of 91 ng/ml.The serum levels of syndecan-1 were elevated in patients with HL, but were not strongly correlated with other potential prognostic factors. Their effect on prognosis deserves further evaluation.
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- 2005
37. Differential diagnosis of Waldenstrom's macroglobulinemia and other B-cell disorders
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Christina Kalpadakis, Maria K. Angelopoulou, Panagiotis Tsaftaridis, Flora N. Kontopidou, Maria-Christina Kyrtsonis, Evangelia M. Dimitriadou, Styliani I. Kokoris, P Panayiotidis, Kaliroe Tsalimalma, Tatiana Tzenou, Theodoros P. Vassilakopoulos, Marina P. Siakantaris, Maria N. Dimopoulou, and Gerassimos A. Pangalis
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Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Lymphoma ,Chronic lymphocytic leukemia ,Follicular lymphoma ,Lymphoma, Mantle-Cell ,Diagnosis, Differential ,immune system diseases ,hemic and lymphatic diseases ,Gammopathy ,medicine ,Humans ,Splenic marginal zone lymphoma ,Aged ,Retrospective Studies ,business.industry ,Gene Expression Profiling ,Macroglobulinemia ,Middle Aged ,medicine.disease ,Cryoglobulinemia ,Leukemia, Lymphocytic, Chronic, B-Cell ,Immunoglobulin M ,Mantle cell lymphoma ,Female ,Waldenstrom Macroglobulinemia ,business - Abstract
Waldenstrom's macroglobulinemia (WM) is characterized by lymphoplasmacytic infiltration of bone marrow and/or other tissues and by the presence of serum monoclonal immunoglobulin M ([IgM], without cutoff limit). Differential diagnosis from other B-cell disorders (BCDs) is usually easy based on clinical, morphologic, histopathologic, immunophenotypic, and genetic features. However, all BCDs potentially produce monoclonal IgM. In this study we reviewed the medical files of 130 patients with IgM-secreting BCDs. Eighty-four patients were diagnosed with WM, 5 with IgM-monoclonal gammopathy of undetermined significance (MGUS), and 41 with other BCDs (9 with B-cell chronic lymphocytic leukemia, 5 with small lymphocytic lymphoma, 14 with marginal zone lymphoma, 5 with mantle-cell lymphoma, 2 with follicular lymphoma, 2 with diffuse large B-cell lymphoma, 2 with cryoglobulinemia, and 2 with low-grade lymphoma not otherwise specified). Median IgM levels were 3215 mg/dL in WM, 840 mg/dL in IgM-MGUS, and 285 mg/dL in other BCDs (5 had IgM levels > 1500 mg/dL). In 10% of non-WM BCDs, monoclonal IgM was found only when more sensitive immunofixation methods were used. Forty-four percent of patients with BCDs (splenic marginal zone lymphoma or small lymphocytic lymphoma) had diagnoses that corresponded to that of WM. Careful diagnosis requires the concomitant evaluation of all parameters of BCDs together. Marginal zone lymphoma is the most frequently overlapping entity. Special attention should be given to mantle cell lymphoma in its atypical forms. Research in this field should continue to further clarify the disease entities that overlap with WM. New technology such as gene-expression profile techniques may contribute to this purpose.
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- 2005
38. Chapter 8 The Contribution of Prognostic Factors to the Better Management of Multiple Myeloma Patients
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Marie-Christine Kyrtsonis, Dimitrios Maltezas, Efstathios Koulieris, Katerina Bitsani, Ilias Pessach, Anna Efthymiou, Vassiliki Bartzis, Tatiana Tzenou, Panayiotis Panayiotidis, Marie-Christine Kyrtsonis, Dimitrios Maltezas, Efstathios Koulieris, Katerina Bitsani, Ilias Pessach, Anna Efthymiou, Vassiliki Bartzis, Tatiana Tzenou, and Panayiotis Panayiotidis
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- 2012
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39. Evaluation Of Immunoglobulin Variations (Clonal Changes) In Symptomatic Multiple Myeloma (MM) Patients’ Course
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Vassiliki Bartzis, Panayiotis Panayiotidis, Dimitrios Maltezas, Anna Efthymiou, Theodoros Iliakis, Panagiotis Tsaftaridis, Ilias Pessach, Nikolitsa Kafasi, Tatiana Tzenou, Efstathios Koulieris, Katerina Sarris, Eftychia Nikolaou, Marie-Christine Kyrtsonis, Ioanna Vardounioti, Theodoros P. Vassilakopoulos, Vassiliki Karali, Maria K. Angelopoulou, Nora Vyniou, and Maria Dimou
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Immunoglobulin A ,medicine.medical_specialty ,biology ,business.industry ,Immunology ,Clone (cell biology) ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Immunoglobulin D ,Gastroenterology ,Immunoglobulin G ,Internal medicine ,Monoclonal ,biology.protein ,medicine ,Antibody ,business ,Survival analysis ,Multiple myeloma - Abstract
Changes in the production of monoclonal intact immunoglobulin (M-Ig) or of serum free light chains (sFLC) during symptomatic MM patients’ relapse eventually reflect molecular myeloma cells changes and / or reveal clonal cell competition. We aimed to study changes in Ig production (CIg) in symptomatic MM patients and to evaluate related frequency and corresponding specific disease characteristics. Patients and Methods 232 symptomatic MM patients with available follow-up sFLC measurements, were retrospectively studied. Light chain escape (LCE) was defined as sFLC increase with stable or falling M-Ig concentrations, M-Ig escape (MCE) as decreasing sFLC with increasing M-Ig, de-differentiation (DD) as clinical relapse with normal or decreased M-Ig and sFLC and Clonal Domination (CD) as normalization of formerly increased IgG, IgA or FLC in relapsing patients presenting increase of another component. Survival was calculated from diagnosis or from CIg date to last follow-up or death, survival curves were plotted by Kaplan-Meyer Method and assessed by the log-rank test. Results There were 94 women and 128 men, median aged 66 years; 29%, 42%, 29% and 22%, 30%, 48% were in Durie-Salmon and ISS stages I, II, III and 1, 2, 3 respectively. MM type was IgG MM in 59%, IgA in 21%, light chain only in 17%, IgD in 2% and non-secretory in1%. Median survival of the whole cohort was 46,4 months. CIg was observed in 39 patients (17%), consisting in LCE in 15 patients (6%), MCE in 7 (3%), DD in 5 (2%) and CD in 10 (4%); two additional patients (1 IgD and 1 LC) transiently produced another monoclonal component that was IgG in both cases, while in stringent complete remission. In CD patients, the dominated clone was IgG in 9 out of 10 patients, while the dominating one was LC in 8 and IgA in 2. LCE and MCE were more frequent in IgG patients. The median number of treatment lines received prior CIg was 5 for LCE, 4 for MCE, 2 for DD and 1 for CD. LCE and MCE patients had all received novel agents and/or ASCT. The median time from CIg to last follow-up or death was 2,6 months (2,2-3) for LCE, 3,3 months (2,2-4,4) for MCE, 6,3 months (1,1-11,6) for DD and 31,1 months (23,6-38,6) for CD. Patients presenting LCE, MCE and DD had a considerably shorter survival after CIg compared to patients presenting CD (p=0,0002). However because CIg was usually a late event in the course of the disease the overall survival of CIg patients was 60,6 months. In conclusion, LCE, MCE and DD are late events in the course of MM, mainly observed in patients whose previous treatments included with novel drugs. They reflect a very aggressive disease behavior with shortened survival thereafter, probably due to the emergence of a new resistant clone. CD was mainly observed in patients secreting low IgG levels and FLCs, and possibly reflect IgG clone remission in biclonal patients, given that thereafter, the disease behaves as a usual multiple myeloma, secreting however the other clone. Disclosures: No relevant conflicts of interest to declare.
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- 2013
40. Clonotypic Analysis Of Immunoglobulin Heavy Chain (IgH) Sequences In Patients With Waldenström’s Macroglobulinemia. Correlation With MYD88 L265P Somatic Mutation Status, Clinical Features and Outcome
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Loizos Petrikkos, Marie-Christine Kyrtsonis, Anna Efthymiou, Dimitrios Maltezas, Tatiana Tzenou, Panayiotis Panayiotidis, Maria Roumelioti, and George Georgiou
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Mutation ,Point mutation ,Immunology ,Macroglobulinemia ,Somatic hypermutation ,Cell Biology ,Hematology ,Biology ,medicine.disease_cause ,Biochemistry ,Germline mutation ,medicine ,biology.protein ,Immunoglobulin heavy chain ,Antibody ,IGHV@ - Abstract
Background and aim Waldenström’s Macroglobulinemia (WM) cells express a unique clonotypic rearrangement of heavy chain immunoglobulin (IgH) genes in each individual patient. Recent studies demonstrate high frequency of the MYD88 L265P somatic mutation in patients with WM, implying a new pathway for the pathogenesis of this disease. In this study we characterized clonal IgH genes rearrangements, IGHV gene use, somatic hypemutations (SHM) and presence of the ΜΥD88 L265P mutation in a cohort of WM patients and we investigated any eventual correlation with patients’ clinical features. Patients and methods 36 patients with WM were studied (median age 64y, 19 males and 17 females, symptomatic 72%, asymptomatic 28%) of whom 45%, 39% and 16% were stage IPSSWM 1, 2 and 3, respectively. Median time to treatment initiation was 13 months and median overall survival was 61 months. DNA was extracted from patients’ bone marrow/blood samples and clonal IgH VDJ rearrangements were amplified by PCR using the Biomed-2 Concerted Action protocol. Monoclonal VDJ rearranged PCR fragments were sequenced and analyzed using the IMGT database (www.imgt.org). Thirty-one patients’ DNA samples were also analyzed for the presence of the ΜΥD88 L265P mutation by using a mutation specific PCR assay. Results The most frequent clonal rearrangements observed in our patients were in the IGVH3 family (73% of cases); the IGVH3-23 gene and the IGVH3-74 gene were used in 24.4% and 18,9% of cases, respectively. Somatic hypermutation (>2%) was seen in all but three cases (92%). Mean percentage of mutations in all cases, IGVH3 family, IGVH3-23 and IGVH3-74 genes was 7,5%, 8%, 9,4% and 7,5%, respectively. Sixty-two percent of the patients were positive for the ΜΥD88 L265P mutation and notably all three unmutated WM cases were negative for this MYD88 point mutation. No correlation between VH or DH gene usage, CDR3 length, and mutational status with clinical parameters, time to treatment initiation, or survival was found. Conclusions WM IgH genes repertoire, as expected, differs from that observed in normal B-cells and other B-cell diseases such as MZL, MCL and B-CLL/SLL. In addition to the known hyper-representation of the IGVH3-23 gene, another member of the VH3 family, the IGVH3-74 gene is also over-represented in WM. The high IGVH mutation rate supports a derivation of WM cells from postgerminal center memory B cells in the majority (92%) of WM patients. However, the identification of a minority of WM patients (3 of 36) with unmutated IGHV gene segments, negative for the ΜΥD88 L265P mutation, supports the hypothesis that they represent a subgroup of WM not arising from post-germinal B cells with a different disease pathogenesis. Disclosures: No relevant conflicts of interest to declare.
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- 2013
41. The Presence Of Spine Bone Plasmacytomas At The Time Of Multiple Myeloma (MM) Diagnosis Confers Poor Prognosis
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Marie-Christine Kyrtsonis, Eftychia Nikolaou, Dimitrios Maltezas, Katerina Sarris, Efstathios Koulieris, Theodoros Iliakis, Nora Vyniou, Ioanna Vardounioti, Vassiliki Karali, Ilias Pessach, Vassiliki Bartzis, Tatiana Tzenou, Maria Dimou, Theodoros P. Vassilakopoulos, Maria K. Angelopoulou, Panagiotis Tsaftaridis, Irene Katodritou, and Panayiotis Panayiotidis
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medicine.medical_specialty ,business.industry ,Immunology ,Context (language use) ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Surgery ,Thalidomide ,Transplantation ,Internal medicine ,Cohort ,medicine ,Plasmacytoma ,Stage (cooking) ,business ,Multiple myeloma ,medicine.drug ,Lenalidomide - Abstract
The negative prognostic consequences of extramedullary plasmacytomas in the context of symptomatic MM is well known. On the contrary, the clinical impact of bone plasmacytomas (BP) has not been extensively studied, although their presence is one of Duries’ major MM diagnostic criteria. The aim of the present study was to study eventual differences between MM patients presenting at diagnosis with or without BP. Patients and Methods Two hundred and twelve symptomatic MM patients were studied from diagnosis to last follow-up. Their median age was 66 years and 60% were men. Twenty-three percent, 27% and 50% of patients were in ISS stage 1, 2 and 3 respectively; MM type was IgG in 59% , IgA in 26%, light chain only in 12%, IgD in 1,5% and non- or oligo-secretory in 1,5%. All patients required treatment and BP ones were additionally given radiotherapy. The median follow-up time of the whole cohort was 46,4 months. Results Forty patients (19%) had a BP at the time of their diagnosis. BP was located in the spine (BP-S) in 19 out of 40 and in other sites (BP-O: skull, pelvis, long bones, and ribs) in 21 patients. BP patients had equivalent demographics, stage and MM type as the others. Non-BP patients tended to have a better survival than BP ones but the difference was not statistically significant (p=0.1). However, BP-S patients had a significantly worse outcome than BP-O patients (24±6 versus 48±11 months, p In conclusion, MM patients presenting spine plasmacytoma at diagnosis constitute a distinct subgroup with adverse outcome that is difficultly predictable, given that the current staging system does not separate them. Further confirmation of this finding in larger cohorts is needed, as well as exploration of the biologic background. Disclosures: No relevant conflicts of interest to declare.
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- 2013
42. Contribution of new immunoglobulin-derived biomarkers in plasma cell dyscrasias and lymphoproliferative disorders
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Stephen Harding, Dimitrios Maltezas, Marie-Christine Kyrtsonis, Efstathios Koulieris, and Tatiana Tzenou
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medicine.anatomical_structure ,biology ,business.industry ,Immunology ,biology.protein ,medicine ,Lymphoproliferative disorders ,Antibody ,Plasma cell ,business ,medicine.disease ,Dyscrasia - Abstract
Contribution of new immunoglobulin-derived biomarkers in plasma cell dyscrasias and lymphoproliferative disorders
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- 2013
43. Increased Serum Transforming Growth Factor-beta1 (Tgf-beta1) Is Related to a Better Outcome in MM, WM and CLL Patients
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Maria Dimou, Efstathios Koulieris, Maria Gavriatopoulou, Meletios A. Dimopoulos, Katerina Sarris, Panayiotis Panayiotidis, Vassiliki Bartzis, Eftychia Nikolaou, Marie-Christine Kyrtsonis, Maria K. Angelopoulou, Evangelos Terpos, Tatiana Tzenou, Dimitrios Maltezas, Gerasimos Pangalis, and Theodoros P. Vassilakopoulos
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medicine.medical_specialty ,biology ,Beta-2 microglobulin ,Anemia ,business.industry ,Chronic lymphocytic leukemia ,Immunology ,Waldenstrom macroglobulinemia ,Macroglobulinemia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Immunoglobulin D ,Gastroenterology ,Surgery ,Median follow-up ,Internal medicine ,biology.protein ,medicine ,business ,Multiple myeloma - Abstract
Abstract 4976 Background and Aims: TGF-beta1 normally down-regulates B-cell proliferation. Resistance to its effects is reported in malignant cells of B-lineage such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) cells. There are however very few studies on serum TGF-beta1 levels in patients with B-cell lymphoproliferative diseases and their eventual correlations with parameters of disease activity and survival. The purpose of our study was to assess any eventual relationship between serum TGF-beta1 levels and disease parameters, as well as time to first treatment (TFT) and overall survival (OS) in a series of MM, Waldenstrom's macroglobulinemia (WM) and CLL patients at diagnosis. Patients and Methods: 92 MM, 64 WM and 110 CLL patients were studied. In the MM group, paraprotein was IgG in 64, IgA in 18, LC in 8 and IgD in 2 patients while 32, 25 and 43% of patients were in ISS stage 1, 2 and 3 respectively. MM patients' median follow-up was 51 months. All patients required treatment a some point, 55% immediately. In the WM group, 44, 27 and 29% of patients were in WM – IPSS stage 1, 2 and 3 respectively. WM patients' median follow-up was 49 months; 75% of them required treatment during follow – up. In the CLL group, 54% and 74%, 25% and 20%, 14% και 6%, were in stage 0 and A, 1 and β, 2 and C according to Rai and Binet respectively. Median follow up was 43 months; 14 patients needed immediate treatment, 30 more required treatment during follow up while the others are still just followed. Patients' frozen sera, drawn at diagnosis, were retrospectively analyzed while sera from 20 healthy individuals (HI) were tested as controls. Serum TGF-beta1 measurements were done by ELISA according to the manufacturer's instructions. Statistical analysis was performed by SPSS software, version 15. 0. Results: Median serum TGF-beta1 levels were 36330 pg/ml (range 4. 6 – 77976) in MM patients, 33965 pg/ml (range 1665–615000 pg/ml) in WM, 12207 pg/ml in CLL (range 0 – 42970) and 32902 pg/ml in HI (range 1941 – 58123). CLL patients presented significantly lower TGF-beta1 levels than those with MM and WM (p Conclusions: Our results of longer TFT in MM and CLL and improved OS in MM and WM patients with increased serum TGF-beta1 levels, suggest that a degree of sensitivity to the suppressive effect of TGF-beta1 may remain in neoplastic B-cells in the majority of B-cell lymphoproliferative disorders. Disclosures: No relevant conflicts of interest to declare.
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- 2012
44. A Shorter Time to First Treatment and Worst Overall survival Is Observed in Cll Patients with Reduced Serum IgM As Evaluated with Novel Serum Immunoassays
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Maria Dimou, Ioanna Vardounioti, Nikolitsa Kafasi, Dimitrios Maltezas, Theodoros P. Vassilakopoulos, Anna Efthymiou, Tatiana Tzenou, Maria K. Angelopoulou, Marie-Christine Kyrtsonis, Marina P. Siakantaris, Charis Matsouka, Efstathios Koulieris, Gerasimos Pangalis, Panagiotis Tsaftaridis, Vassiliki Bartzis, Katerina Sarris, Katerina Mpitsanis, Despoina Mparmparousis, Panayiotis Panayiotidis, and Sotirios Sachanas
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medicine.medical_specialty ,education.field_of_study ,biology ,business.industry ,Chronic lymphocytic leukemia ,Immunology ,Population ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Immunoglobulin G ,Hypogammaglobulinemia ,Internal medicine ,medicine ,biology.protein ,Antibody ,business ,education ,Nephelometry ,Survival analysis ,Multiple myeloma - Abstract
Abstract 4585 Background and Aims: Reduced serum IgM levels were proposed as an unfavorable prognostic factor in multiple myeloma1. We therefore investigated the possible impact of decreased serum IgM concentrations on the outcome of Chronic Lymphocytic Leukemia (CLL) patients, a disease that is frequently characterized by severe hypogammaglobulinemia. Serum IgM levels were measured by 2 methods. Patients and methods: 188 patients with CLL were studied. Of them 54%, 27%,10%, 7% και 2% where in RAI stage 0, 1, 2, 3, 4 respectively while 65%, 22% and 13% in Binet stages A, B and C. IgM was determined at diagnosis by both classical nephelometry and the new Hevylite™ methods; the first measures total IgM levels while the second one measures the immunoglobulin fractions bound to either kappa or lambda light chains therefore enabling us to determine the ratio of IgM-kappa/lambda (HLCR). Hevylite™ measurements were retrospectively performed in 69/188 patients with available frozen sera aliquots from drawn at the time of diagnosis. Of them the Ig subclasses IgMkappa and IgMlambda, IgGkappa and IgGlambda, IgAkappa and IgAlambda (HLC) were measured by Hevylite™ antibodies nephelometrically. Light chain restriction (kappa or lambda) was determined by flow cytometry or bone marrow/lymph node biopsy immunohistochemistry. The ratios (HLCRs) were calculate with the monoclonal immunoglobulin as numerator, i.e IgMkappa/IgMlambda, IgGkappa/IgGlambda and IgAkappa,/IgAlambda in kappa-restricted patients and IgMlambda/IgMkappa, IgGlambda/IgGkappa, IgAlambda/IgAkappa in lambda-ones. Serum IgM concentration by both methods were related to time to first treatment (TFT) and overall survival (OS). Statistical analysis was performed conventionally; survival curves were drawn by Kaplan-Meyer method and compared by the log-rank test. Results: Total IgM ranged from 12 to 246 mg/dl (median 47.6). The sum of IgMkappa plus IgMlambda from 12 to 369 (median 60). IgMkappa from 7.9 to 349 mg/dL (median 41) in kappa-restricted patients and IgMlambda from 7.6 ωζ 98 mg/dL (median 22) in lambda restricted ones. Low total IgM level ( Finally IgM-HLCR was abnormal in 35% of patients. Of them, 25% had also abnormal IgG-HLCR and/or IgA-HLCRs leading to the hypothesis of multiple clones coexistence within the neoplastic B-cell lymphocytic population. Conclusions: Low IgM levels determined by novel immunoassays (Hevylite™) correlate to shorter TFT and OS in patients with CLL. Their use may reveal new disease characteristic and are suggestive of a multi-oligoclonal disorder. Disclosures: No relevant conflicts of interest to declare.
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- 2012
45. Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia (cll) Prognosis
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Gerassimos A. Pangalis, Katerina Sarris, Nikolitsa Kafasi, Stephen Harding, Panagiotis Tsaftaridis, Marie-Christine Kyrtsonis, Theodoros P. Vassilakopoulos, Anna Efthymiou, Panayiotis Panayiotidis, Sotirios Sachanas, Maria K. Angelopoulou, Vassiliki Bartzis, Dimitris Maltezas, Eftychia Nikolaou, Marina P. Siakantaris, Maria Dimou, Efstathios Koulieris, Tatiana Tzenou, Katerina Bitsani, and Flora N. Kontopidou
- Subjects
medicine.medical_specialty ,Pathology ,biology ,medicine.diagnostic_test ,business.industry ,Proportional hazards model ,Chronic lymphocytic leukemia ,Immunology ,Hazard ratio ,Serum albumin ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Asymptomatic ,Gastroenterology ,hemic and lymphatic diseases ,Internal medicine ,Biopsy ,biology.protein ,Medicine ,medicine.symptom ,Stage (cooking) ,business ,Nephelometry - Abstract
Abstract 4568 Background and Aim: Symptomatic CLL patients need treatment immediately. For these patients, molecular-genetic factors (mutated-unmutated, ZAP 70, ATM, p53) are important prognostic factors of response and survival. Nevertheless, 2/3 of newly diagnosed patients are asymptomatic and require only of follow up that can last for months or years. For these patients overall survival (OS) depends on the time to first treatment (TFT). The most frequent paraprotein produced in CLL is serum free light chain in 50% of the patients. It has recently been shown that serum free light chains (sFLC) and their sum above 60 (κ+λ above 60) are useful prognostic factors for TFT. We therefore studied the eventual prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients' series. Patients and Methods: 143 CLL patients were studied of which 18 needed immediate treatment while 37 more needed treatment during their follow up. 64% and 72%, 28% and 18%, 7.5% and 10%, were in stage 0 and A, 1 and β, 2 and C according to Rai and Binet respectively. Median patients' follow up was 32 months (range 4–228). Light chain restriction was established by flow cytometry or bone marrow biopsy immunohistochemistry. Serum free light chain values were retrospectively determined by nephelometry (Freelite™, the Binding Site Birmingham, UK) in frozen sera drawn at diagnosis. Elevated sFLC values were defined using as cut-off values the 95th percentile range of healthy individuals. Statistical analysis was performed using SPSS v15.0. Hazard ratios and prognostic significance of abnormal sFLC, HLC and ratios were determined by univariate Cox regression analysis. Kaplan Meier method was used for pictorial representation of survival and time to treatment. Results: Increased sFLC were found in 45% of the patients while the summated FLC-kappa plus FLC-lambda was higher than 60 mg/dl in 14%. Increased sFLC values as well as values of FLC κ+λ>60 were related to shorter TFT (p=0,0005 and p=0,000003 respectively). In addition, high levels of sFLC and FLC κ+λ >60 correlated with β2-microglobulin (r=0.2, p=0.009 και r=0.2, p=0.03 respectively), serum albumin (r=0.2, p=0.009 only for FLC κ+λ > 60), negatively with hemoglobin (r=-0.3, p=0.000003 και r=-0.2, p=0.0002 respectively), increased LDH (p=0.037 και 0.001 respectively), Rai stage (p=0.03 και 0.003 respectively) and Binet stage (p=0.02 only for FLC κ+λ > 60) and with the presence of beta-symptoms (p=0.004 only for FLC κ+λ > 60). Finally, increased sFLC and FLC κ+λ>60 values correlated with shorter OS (p=0.05 and p=0.003 respectively). Conclusion: The results of our study confirmed the significance of sFLC in CLL with regard to TFT and their relationship with adverse prognostic clinical and laboratory parameters but also demonstrated for the first time their impact on OS. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2012
46. Ratio of involved/uninvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma
- Author
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George Georgiou, Stephen Harding, Marie-Christine Kyrtsonis, Panayiotis Panayiotidis, Dimitris Maltezas, Arthur R. Bradwell, Vassiliki Bartzis, Ladan Mirbahai, Maria Dimou, Efstathios Koulieris, Tatiana Tzenou, and Nikolitsa Kafasi
- Subjects
Cancer Research ,medicine.medical_specialty ,Pathology ,Anemia ,Serum immunoglobulin ,Heavy/light chain measurements ,Immunoglobulin light chain ,Gastroenterology ,Asymptomatic ,lcsh:RC254-282 ,HLCR ,Multiple myeloma ,Internal medicine ,medicine ,Hematology ,biology ,business.industry ,lcsh:RC633-647.5 ,Research ,lcsh:Diseases of the blood and blood-forming organs ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Oncology ,biology.protein ,Antibody ,medicine.symptom ,business ,Nephelometry ,Kappa - Abstract
Background HevyLite™ is a new, recently developed method that facilitates separate quantification of the kappa- and lambda-bounded amounts of a given immunoglobulin (Ig). Using this method, we measured intact immunoglobulin (heavy/light chain; HLC) IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda individually, as well as their deriving ratios (HLCR) in a series of IgG or IgA multiple myeloma (MM) patients, to investigate and assess the contribution of these tests to disease evaluation. Patients and methods HevyLite™ assays were used in sera from 130 healthy individuals (HI) and 103 MM patients, at time of diagnosis. In patients, the level of paraprotein was IgG in 78 (52 IgG-kappa, 26 IgG-lambda) and IgΑ in 25 (13 IgΑ-kappa, 12 IgΑ-lambda). Durie-Salmon and International Staging System stages were evenly distributed. Symptomatic patients (n = 77) received treatment while asymptomatic ones (n = 26) were followed. Patients' median follow-up was at 32.6 months. HLCR was calculated with the involved Ig (either G or A) as numerator. Results In HI, median IgG-kappa was 6.85, IgG-lambda 3.81, IgA-kappa 1.19 and IgA-lambda 0.98 g/L. The corresponding median involving HLC values in MM patients were 25.8, 23.45, 28.9 and 36.4 g/L. HLC-IgG related to anemia, high serum free light chain ratio and extensive bone marrow infiltration, while high HLCR correlated with the same plus increased β2-microglobulin. In addition, increased HLCR and the presence of immunoparesis correlated with time to treatment. Patients with high HLCR had a significantly shorter survival (p = 0.022); HLCR retained its prognostic value in multivariate analysis. Conclusions HLC and HLCR quantify the precise amount of the involved immunoglobulin more accurately than other methods; moreover, they carry prognostic information regarding survival in MM patients.
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- 2012
47. Heavy Chain Ratio (HLCR) IgGκ/IgGλ or IgAκ/IgAλ: Experience and Clinical Implications In Multiple Myeloma at Diagnosis and During Disease Course
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Marie-Christine Kyrtsonis, Ladan Mirbahai, George Georgiou, Stephen Harding, Nikolitsa Kafassi, Efstathios Koulieris, Vassiliki Bartzis, Panayiotis Panayiotidis, Maria Dimou, Tatiana Tzenou, Dimitris Maltezas, and Arthur R. Bradwell
- Subjects
medicine.medical_specialty ,biology ,Bone disease ,business.industry ,Immunology ,Cell Biology ,Hematology ,Plasma cell ,medicine.disease ,Biochemistry ,Gastroenterology ,Asymptomatic ,Immunoglobulin G ,medicine.anatomical_structure ,Internal medicine ,Monoclonal ,biology.protein ,Medicine ,Stage (cooking) ,Antibody ,medicine.symptom ,business ,Multiple myeloma - Abstract
Abstract 5019 A new method for the quantification of IgGκ, IgGλ, IgAκ and IgAλ individually and of deriving IgGκ/IgGλ and IgAκ/IgAλ ratios (HLCR) has been recently made available, allowing measurements of the monoclonal component alone as well as of the polyclonal, non-tumor immunoglobulins (Ig) in plasma cell dyscrasias. The purpose of the present study was to retrospectively determine HLCR and to investigate its contribution in a series of 98 multiple myeloma patients at presentation and in 38 of them, during their disease's course. There were 45 women and 53 men (median age 67 years). Disease stages were evenly distributed (36%, 30%, and 34% in ISS stage 1, 2, and 3 respectively). Paraprotein was IgG in 74 patients (50 IgGκ, 24 IgGλ) and IgA in 24 (12 IgAκ, 12 IgAλ) of them. Seventy-one symptomatic patients received conventional treatment while the other 27 were asymptomatic and were regularly followed only. Of the 38 patients also studied during disease course, 28 had IgG- and 10 IgA-MM; the median number of disease fluctuation events studied (remision-relapse) was 3 (range 2–9). Patients' median follow-up was 31 months. HLC analyses were performed on a Dade Behring BN™II nephelometer using polyclonal sheep antibodies (Hevylite™, Binding Site, UK) and HLCR was calculated with the involved Ig (either G or A) as numerator. HLC and HLCR values were then compared with disease parameters and survival. Statistical analysis was performed by standard methods. At patients' presentation, median monoclonal HLC IgG and IgA were 25 g/L and 32 g/L respectively while in patients with IgG-MM median IgG HLCR was 24.5 and IgA HLCR 60 in IgA-MM. HLCR was not correlated to b2-microglobulin, hypercalcemia, LDH or bone disease, FLCs or FLCR. It strongly correlated with time to treatment (p=0.0000093) and with a shorter overall survival (p=0.03) using as cut-0ff HLCR values in the upper tertile of symptomatic patients (>56 for IgG and >228 for IgA). Of patients also studied during their disease course, 25 out of 38 patients responded at least partially (PR) to first line treatment and 9 to a subsequent one; 20 relapsed and then responded again. In most patients HLCR followed disease fluctuations. It normalized in 9 patients and was below normal in 1 patient that achieved a complete (CR) or stringent response (sCR). In some patients HLCR allowed a better evaluation of disease status. In 5 thought to be responding, ηLCR remained stable or increased and disease course confirmed the fragility of the believed response. Interestingly, more than 50% of patients that received VAD showed greater reduction of the polyclonal Ig than the tumor Ig during treatment and sometimes thereafter. In conclusion, we provide evidence that HLCR correlates with survival in MM and allows, in some patients, better disease monitoring. Disclosures: Mirbahai: Binding Site Group Ltd: Employment. Bradwell:Binding Site: Equity Ownership, Patents & Royalties. Harding:Binding Site Group Ltd: Employment.
- Published
- 2010
48. Quantification of Serum IgMκ and IgMλ In Patients with Waldenstrom's Macroglobulinemia (WM) at Diagnosis and During Disease Course; Clinical Correlations
- Author
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Vassiliki Bartzis, George Georgiou, Stephen Harding, Efstathios Koulieris, Tatiana Tzenou, Charis Matsouka, Maria Dimou, Arthur R. Bradwell, Dimitris Maltezas, Ladan Mirbahai, Panayiotis Panayiotidis, Gerasimos Pangalis, Marie-Christine Kyrtsonis, and Nikolitsa Kafassi
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,biology ,business.industry ,Immunology ,Hypergammaglobulinemia ,Macroglobulinemia ,Waldenstrom macroglobulinemia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Hypogammaglobulinemia ,Internal medicine ,Serum protein electrophoresis ,Monoclonal ,medicine ,biology.protein ,Antibody ,business ,Nephelometry - Abstract
Abstract 3004 Resolution of IgM monoclonal proteins (M-proteins) on serum protein electrophoresis (SPE) can make accurate quantification difficult. The same applies to the determination of total IgM by nephelometry which inherently includes monoclonal and polyclonal immunoglobulins. Specific polyclonal antibodies, which recognise epitopes spanning the junction of the heavy and light chains of the individual immunoglobulin isotypes, have been produced and used to develop nephelometric assays (Hevylite™). The purpose of the present study is to evaluate the prognostic value IgMκ/IgMλ ratios (HLCR) at diagnosis and the role of HLCR in disease monitoring. Retrospective sera from 31 WM patients, 4 IgM-MGUS, 2 IgM-like syndrome at diagnosis and for 9 of them during disease course, were included in the study. Analysis of IgMκ and IgMλ was performed on a Siemens Dade-Behring BN™II nephelometer and results were compared with disease parameters such as blood count, beta2-microglobulin (β2M), serum albumin, lactate dehydrogenase (LDH), and lymphoplasmacytic bone marrow infiltration. Abnormal HLCR were reported in 30/31 WM patients. There was a good correlation between summated IgMκ + IgMλ and total IgM (r=0.832 p0.01). These 12 patients presented polyclonal hypogammaglobulinemia (with regard to their IgG and IgA levels). Median IgM HLCR (expressed as IgMκ/IgMλ or IgMλ/IgMκ with the involved Ig as numerator) were 90.88 (range 1.91–1000) in WM v 17.65 (range 1.08–34.57) in IgM-MGUS (p=0.06). Median IgM HLCR was significantly higher in WM patients requiring treatment (n=24) at presentation than in patients not (n=7) requiring treatment (185.7 v 13.45 p=0.023). IgM HLCR correlated with bone marrow infiltration (p=0.029) and time to first treatment (p=0.003). A simple risk stratification model utilising: IgM HLCR>median, β2M>5 and abnormal LDH, identified 3 prognostic groups with respect to survival (p Disclosures: Mirbahai: Binding Site Group Ltd: Employment. Bradwell:Binding Site: Equity Ownership, Patents & Royalties. Harding:Binding Site Group Ltd: Employment.
- Published
- 2010
49. Genetic and molecular mechanisms in multiple myeloma: a route to better understand disease pathogenesis and heterogeneity
- Author
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Tatiana Tzenou, George Georgiou, Xenophon Papanikolaou, Marie-Christine Kyrtsonis, Efstathios Koulieris, Vassiliki Bartzis, Panayiotis Panayiotidis, and Maria Dimou
- Subjects
genetic abnormalities ,Chromosomal translocation ,Review ,Disease ,Biology ,Bioinformatics ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Genetics (clinical) ,Multiple myeloma ,030304 developmental biology ,Chromosome 13 ,0303 health sciences ,pathogenesis ,Chromosome ,Plasma cell neoplasm ,medicine.disease ,3. Good health ,myeloma ,Immunoglobulin class switching ,030220 oncology & carcinogenesis ,prognosis ,heterogeneity - Abstract
Multiple myeloma (MM) is a heterogeneous plasma cell neoplasm presenting with a wide range of clinical manifestations. In spite of the availability of very performing treatment modalities, survival is highly varying, ranging from a few months to several years. Underlying genetic and microenvironmental mechanisms are thought to be responsible for clinical heterogeneity. Disease etiology is unknown but progresses in the understanding of its pathogenesis have shown that MM precursor cell transformation into a malignant one occurs in a multistep process. Possibly during class switch recombination a primary genetic event takes place. With the occurrence of additional events and the support of bone marrow microenvironmental cells, neoplastic plasma cells actively proliferate and disease behavior may change. Recurrent translocations involving the IgH locus (11q13, 4p16, 16q23, 21q12, and 6p21), deletions of chromosome 13, trisomies of chromosomes 3, 5, 9, 11, 15, 19, and 21, and dysregulated expression of cyclin D genes, are considered initiating or primary events. Alterations related to further disease transformation and adverse prognosis are deletion of 17p13, c-myc translocations, and gains of chromosome 1q21. In relation to the underlying genetic defects, disease subgroups are recognized. Accordingly treatment effectiveness may differ among groups. Intense research is ongoing in this field.
- Published
- 2010
50. Increased Immunohistochemical CD138 Expression in Waldenström's Macroglobulinemia (WM) in Comparison with Splenic Marginal Zone Lymphoma (SMZL)
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Theodoros P. Vassilakopoulos, Athina Androulaki, Dimitrios Maltezas, Vasiliki Bartzi, Penelope Korkolopoulou, Maria K. Angelopoulou, Spyros I. Siakavellas, Efstathios Koulieris, Marie-Christine Kyrtsonis, Georgios Georgiou, Styliani Kokkoris, Eystathios Patsouris, Tatiana Tzenou, Maria Dimou, Christina Kalpadakis, Panayiotis Panayiotidis, Gerasimos Pangalis, and Georgia Levidou
- Subjects
Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Chronic lymphocytic leukemia ,Immunology ,Macroglobulinemia ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Lymphoma ,medicine.anatomical_structure ,Immunophenotyping ,hemic and lymphatic diseases ,Biopsy ,medicine ,Bone marrow ,Splenic marginal zone lymphoma ,CD5 ,business - Abstract
Abstract 5008 Introduction Differentiating Waldenström's Macroglobulinemia (WM) from other lymphomas and especially Splenic Marginal Zone lymphoma (SMZL), which presents common features with WM, consists a challenge. There is no characteristic molecular abnormality neither for WM nor for SMZL, while in addition, serum IgM cut off is no longer used for the diagnosis of WM. Moreover, while paratrabecular and intrasinusoidal pattern of bone marrow infiltration are described as typical of WM and SMZL respectively, there is often overlap between them. B-lymphocytes' immunophenotype is usually CD5 and CD23 negative in both entities, although deviations from this pattern may be observed; CD38, a marker of lymphocyte activation, theoretically related to lymphoplasmacytic differentiation and adverse prognosis in Chronic Lymphocytic Leukemia, may be expressed. Both WM and SMZL are included among the least reproducible diagnoses of the WHO classification when the diagnosis is based only on clinical grounds, routine laboratory tests and bone marrow biopsy (absence of lymph node or spleen biopsy or typical leukemic picture). CD138 (Syndecan) is expressed in immature as well as in terminally differentiated B-lymphocytes, especially in plasma cells. A strong CD138 expression is observed in myeloma plasma cells. Aim To evaluate firstly whether CD138 is expressed in WM and SMZL and secondly if its expression may help in the differential diagnosis of these entities. Patients and methods 61 patients were studied at presentation, 40 with WM and 21 with SMZL. Among WM patients, 16 were females and 24 males with a median age of 64 years. 57% presented anemia with hemoglobin Results 62% of WM patients presented CD138 expression in contrast with 14% of SMZL patients. Median percentage of total CD138 expression in neoplastic cells in WM was 26.5% (range 2-100%) while in SMZL it was 8% (range 0-30%). These differences were statistically significant (p Conclusions Patients with WM presented increased CD138 expression when compared to SMZL patients. If confirmed in larger series, CD138 expression could help differentiating the two entities. Disclosures No relevant conflicts of interest to declare.
- Published
- 2009
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