60 results on '"Jolanta Gozdzik"'
Search Results
2. Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working PartyResearch in context
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Olaf Penack, Gloria Tridello, Urpu Salmenniemi, Rodrigo Martino, Nina Khanna, Katia Perruccio, Franca Fagioli, Monika Richert-Przygonska, Hélène Labussière-Wallet, Johan Maertens, Charlotte Jubert, Mahmoud Aljurf, Herbert Pichler, Gergely Kriván, Desiree Kunadt, Marina Popova, Melissa Gabriel, Elisabetta Calore, Igor Wolfgang Blau, Fabio Benedetti, Maija Itäla-Remes, Elizabeth de Kort, Domenico Russo, Maura Faraci, Anne-Lise Ménard, Peter von dem Borne, Xavier Poiré, Akif Yesilipek, Jolanta Gozdzik, Zeynep Arzu Yeğin, Lucrecia Yañez, Luca Facchini, Gwendolyn Van Gorkom, Lorenz Thurner, Ulker Kocak, Antònia Sampol, Tsila Zuckerman, Marc Bierings, Stephan Mielke, Fabio Ciceri, Lotus Wendel, Nina Knelange, Malgorzata Mikulska, Dina Averbuch, Jan Styczynski, Rafael de la Camara, and Simone Cesaro
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Invasive ,Aspergillosis ,Stem cell transplantation ,Mortality ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed. Methods: We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints. Findings: 1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2–26.0) and 11.2% (9.6–13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2–3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3–68.9] vs. 70.4 [67.9–72.8]; multivariate HR 1.5 [1.1–2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8–77.4] vs. 79.0% [76.7–81.1]; multivariate HR 1.7 [1.1–2.5]; p = 0.01). Interpretation: Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure. Funding: There was no external funding source for this study.
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- 2024
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3. Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey
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Katarzyna Bobeff, Agata Pastorczak, Zuzanna Urbanska, Walentyna Balwierz, Edyta Juraszewska, Jacek Wachowiak, Katarzyna Derwich, Magdalena Samborska, Krzysztof Kalwak, Iwona Dachowska-Kalwak, Paweł Laguna, Iwona Malinowska, Katarzyna Smalisz, Jolanta Gozdzik, Aleksandra Oszer, Bartosz Urbanski, Maciej Zdunek, Tomasz Szczepanski, Wojciech Mlynarski, and Szymon Janczar
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venetoclax ,ABT-199 ,BH3 mimetics ,acute lymphoblastic leukaemia ,acute myeloid leukaemia ,juvenile myelomonocytic leukaemia ,Pediatrics ,RJ1-570 - Abstract
Venetoclax, the best established BH3-mimetic, is a practice-changing proapoptotic drug in blood cancers in adults. In paediatrics the data are fewer but exciting results were recently presented in relapsed or refractory leukaemias demonstrating significant clinical activity. Importantly, the in-terventions could be potentially molecularly guided as vulnerabilities to BH3-mimetics were re-ported. Currently venetoclax is not incorporated into paediatric treatment schedules in Poland but it has been already used in patients that failed conventional therapy in Polish paediatric haemato-oncology departments. The aim of the study was to gather clinical data and correlates of all paediatric patients treated so far with venetoclax in Poland. We set out to gather this experience to help choose the right clinical context for the drug and stimulate further research. The questionnaire regarding the use of venetoclax was sent to all 18 Polish paediatric haemato-oncology centres. The data as available in November 2022 were gathered and analysed for the diagnoses, triggers for the intervention, treatment schedules, outcomes and molecular associations. We received response from 11 centres, 5 of which administered venetoclax to their patients. Clinical benefit, in most cases consistent with hematologic complete remission (CR), was reported in 5 patients out of ten, whereas 5 patient did not show clinical benefit from the intervention. Importantly, patients with CR included subtypes expected to show venetoclax vulnerability, such as poor-prognosis ALL with TCF::HLF fusion. We believe BH3-mimetics have clinical activity in children and should be available to pae-diatric haemato-oncology practitioners in well-selected applications.
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- 2023
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4. Disseminated Juvenile Xanthogranuloma and Hemophagocytic Lymphohistiocytosis Developed During Treatment of Acute Lymphoblastic Leukemia: Case Report
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Katarzyna Pawińska-Wa̧sikowska, Magdalena Cwiklinska, Elzbieta Wyrobek, Walentyna Balwierz, Karolina Bukowska-Strakova, Agnieszka Dluzniewska, Jolanta Gozdzik, Grazyna Drabik, Monika Rygielska, Konrad Stepien, and Szymon Skoczen
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acute lymphoblastic leukemia ,non-Langerhans cell histiocytosis ,hemophagocytic lymphohistiocytosis ,juvenile xanthogranuloma ,case report ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The association between acute lymphoblastic leukemia (ALL), non-Langerhans cell histiocytosis (non-LCH), and hemophagocytic lymphohistiocytosis (HLH), to the best of our knowledge, has not been published to date. Juvenile xanthogranuloma (JXG), as a type of non-LCH, is usually a benign disease limited to the skin. Systemic involvement is rarely reported. The present case report describes a 15-year-old boy diagnosed with disseminated JXG involving skin and bone marrow concurrent with severe symptoms of HLH during ALL therapy. Examination of immunoglobulin heavy chain genes in B-cell precursor leukemic blasts and histiocytes in the skin and bone marrow revealed identical rearrangements, confirming clonal relationship between both diseases. Implementation of corticosteroids, vinblastine, etoposide, cyclosporine, and tocilizumab resulted in partial skin lesion resolution with no improvement of bone marrow function; therefore, hematopoietic stem cell transplantation (HSCT) was eventually performed. The patient's hematological and general status has improved gradually; however, remarkable recovery of skin lesions was observed after empirical antitubercular therapy. Mycobacterium spp. infection should be considered as a possible secondary HLH trigger. Triple association of ALL, non-LCH, and HLH highlights heterogeneity of histiocytic disorders and possible common origin of dendritic and lymphoid cells.
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- 2020
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5. Supplementary figure 2 from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
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Overall survival of patients with Nijmegen breakage syndrome depending on the time when they were treated due to malignancies: before and after 2000 year.
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- 2023
6. Supplementary figure 1 from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
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The dynamics of primary cancer incidence among patients with NBS described using the three-stage joint-point model.
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- 2023
7. Supplementary Figure 3 from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
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Overall survival of patients with Nijmegen breakage syndrome after cancer diagnosis. Patients who underwent HSCT were marked with an asterix.
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- 2023
8. Supplementary Data legend from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
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Supplementary Data legend
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- 2023
9. Supplementary Table 1 from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
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Supplementary Table 1
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- 2023
10. Epidemiology, Outcome and Risk Factors Analysis of Viral Infections in Children and Adolescents Undergoing Hematopoietic Cell Transplantation: Antiviral Drugs Do Not Prevent Epstein–Barr Virus Reactivation
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Jolanta Gozdzik, Natalia Bartoszewicz, Przemyslaw Galazka, Magdalena Dziedzic, Krzysztof Czyżewski, Olga Zajac-Spychala, Małgorzata Salamonowicz, Ewa Demidowicz, Agnieszka Zaucha-Prażmo, Jowita Fraczkiewicz, and Jan Styczyński
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0301 basic medicine ,viral infections ,030106 microbiology ,medicine.disease_cause ,Virus ,03 medical and health sciences ,infectious complications ,0302 clinical medicine ,Pharmacotherapy ,children ,EBV ,immune system diseases ,hemic and lymphatic diseases ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Risk factor ,Original Research ,Pharmacology ,Acute leukemia ,risk factors analysis ,business.industry ,medicine.disease ,BK virus ,Transplantation ,surgical procedures, operative ,Graft-versus-host disease ,Infectious Diseases ,Infection and Drug Resistance ,HCT ,Immunology ,Rituximab ,business ,medicine.drug - Abstract
Krzysztof Czyzewski,1 Magdalena Dziedzic,1 Malgorzata Salamonowicz,2 Jowita Fraczkiewicz,2 Olga Zajac-Spychala,3 Agnieszka Zaucha-Prazmo,4 Jolanta Gozdzik,5 Przemyslaw Galazka,6 Natalia Bartoszewicz,1 Ewa Demidowicz,1 Jan Styczynski1 1Department of Pediatric Hematology and Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland; 2Department of Pediatric Transplantation, Oncology and Hematology, Medical University, Wroclaw, Poland; 3Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznan, Poland; 4Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical University, Lublin, Poland; 5Stem Cell Transplant Center, University Children’s Hospital, Department of Clinical Immunology and Transplantology, Jagiellonian University Collegium Medicum, Krakow, Poland; 6Department of General and Oncological Surgery for Children and Adolescents, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, PolandCorrespondence: Krzysztof CzyzewskiDepartment of Pediatric Hematology and Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Ul. Sklodowskiej-Curie 9, Bydgoszcz 85-094, PolandTel +48 52 585 48 60Fax +48 52-585 4087Email k.czyzewski@cm.umk.plObjective: The analysis of epidemiology, risk factors and outcome of viral infections in children and adolescents after hematopoietic cell transplantation (HCT).Methods: In this multicenter nationwide study a total of 971 HCT procedures (741 allo-HCT; 230 auto-HCT) over a period of 6 years were analyzed.Results: During this period 801 episodes of viral infections were diagnosed in 442 patients. The incidence of viral infections was 57.9% in allo-HCT and 4.8% in auto-HCT patients. The most frequent infections after allo-HCT were caused by cytomegalovirus (CMV), polyoma BK virus (BKV) and Epstein–Barr virus (EBV). The majority of infections occurred within the first 4 months after allo-HCT and over 80% required pharmacotherapy or symptomatic therapy. The median time of treatment of specific viral infection ranged from 7 (for EBV) to 24 (for CMV) days. The highest mortality was observed in case of CMV infection. The risk factors for viral infections were allo-HCT, acute leukemia, acute and chronic graft versus host disease (a/cGVHD), and matched unrelated donor (MUD)/mismatched unrelated donor (MMUD)-HCT. The risk factor for death from viral infection were CMV-IgG seropositivity in acute lymphoblastic leukemia recipient, and MUD/MMUD-HCT. The incidence of EBV infection requiring pre-emptive treatment with rituximab in allo-HCT children was 19.3%. In 30.8% cases of EBV infection, these episodes were preceded by other viral infection and treated with antivirals, which did not prevent development of EBV-DNA-emia with need of rituximab treatment in 81.5% cases. In 47.7% of these cases, GVHD was a factor enabling development of significant EBV-DNA-emia during antiviral therapy of other infection.Conclusion: We have shown that antiviral drugs do not prevent EBV reactivation in allo-HCT pediatric patients.Keywords: children, EBV, HCT, infectious complications, risk factors analysis, viral infections
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- 2019
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11. „Ми з Вами' (We Stand with You) – saving child war refugees from Ukraine by haematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy in Poland
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Tomasz Jarmoliński, Anna Fałkowska, Krzysztof Czyżewski, Agnieszka Sobkowiak-Sobierajska, Jolanta Goździk, Iwona Malinowska, Katarzyna Drabko, Jan Styczyński, Jacek Wachowiak, Paweł Łaguna, Marek Ussowicz, Oleksandr Istomin, Oleksandr Lysytsia, Wojciech Młynarski, and Krzysztof Kałwak
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poland ,ukraine ,children war refugees ,haematopoietic stem cell transplantation ,car-t cell therapy. ,Pediatrics ,RJ1-570 - Published
- 2024
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12. Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006-2014 European cohort
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Rita Beier, Marina Cavazzana, Figen Dogu, Yves Bertrand, Paul Veys, Francesca Ferrua, Robbert G. M. Bredius, Roland Meisel, Arnalda Lanfranchi, Renata Formankova, Stéphane Blanche, Virginie Courteille, Elena Soncini, Tayfun Güngör, Jolanta Gozdzik, Kim Vettenranta, Krzysztof Kałwak, Mikael Alligon, Natacha Entz-Werle, Ansgar Schulz, Nizar Mahlaoui, Savaş Kansoy, Wilhelm Friedrich, Amos Toren, Mehmet A. Yeşilipek, Alina Ferster, Andrew R. Gennery, Mary Slatter, Despina Moshous, Fulvio Porta, Marco Zecca, Anders Fasth, Karoline Ehlert, Gérard Michel, Bénédicte Neven, Victoria Bordon, Alphan Kupesiz, Mikael Sundin, Kanchan Rao, Cristina Diaz-de-Heredia, Isabelle Badell Serra, Michael H. Albert, Herbert Pichler, Arjan C. Lankester, Andrew J. Cant, Marta González-Vicent, Petr Sedlacek, Jose Moraleda, Caroline A. Lindemans, Peter Bader, Manfred Hoenig, Alain Fischer, Austen Worth, Dmitry Balashov, Erik G J von Asmuth, Carsten Speckmann, Nuno Miranda, Aydan Ikinciogullari, Clinicum, Children's Hospital, Lastentautien yksikkö, HUS Children and Adolescents, University of Zurich, Lankester, Arjan C, Institut Català de la Salut, [Lankester AC, von Asmuth EGJ] Pediatric Stem Cell Transplantation Program and Laboratory for Pediatric Immunology, Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden, The Netherlands. [Neven B] Unité d’Immuno-hematologie et Rhumatologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. Université de Paris, Paris, France. Institut Imagine, INSERM UMR1163, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Paris, France. [Mahlaoui N, Courteille V, Alligon M] French National Reference Center for Primary Immunodeficiencies (CEREDIH) and European Registry for Stem Cell Transplantation for Primary Immunodeficiencies (SCETIDE), Hôpital Universitaire Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. [Diaz-de-Heredia C] Servei d’Oncologia i Hematologia Pediàtriques, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Oncology ,Transplantation Conditioning ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Cohort Studies ,0302 clinical medicine ,conditioning ,Immunology and Allergy ,OUTCOMES ,0303 health sciences ,Otros calificadores::Otros calificadores::/genética [Otros calificadores] ,Hematopoietic Stem Cell Transplantation ,immune reconstitution ,3. Good health ,surgical procedures, operative ,medicine.anatomical_structure ,Cohort ,2723 Immunology and Allergy ,SURVIVAL ,Malalties congènites ,Unrelated Donors ,medicine.medical_specialty ,Immunology ,610 Medicine & health ,pretransplantation infections ,SCID ,03 medical and health sciences ,Internal medicine ,enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades del recién nacido::inmunodeficiencia combinada grave [ENFERMEDADES] ,Other subheadings::Other subheadings::/genetics [Other subheadings] ,medicine ,Humans ,genetic subgroups ,Interleukin-7 receptor ,030304 developmental biology ,Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Infant, Newborn, Diseases::Severe Combined Immunodeficiency [DISEASES] ,2403 Immunology ,Severe combined immunodeficiency ,Cèl·lules mare hematopoètiques - Trasplantació ,business.industry ,medicine.disease ,Anti-thymocyte globulin ,Transplantation ,RECONSTITUTION ,Graft-versus-host disease ,10036 Medical Clinic ,3121 General medicine, internal medicine and other clinical medicine ,Severe Combined Immunodeficiency ,Bone marrow ,business ,030215 immunology - Abstract
Genetic subgroups; Immune reconstitution; Pretransplantation infections Subgrupos genéticos; Reconstitución inmune; Infecciones previas al trasplante Subgrups genètics; Reconstitució immune; Infeccions prèvies al trasplantament Background Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome. Objective We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome. Methods HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed. Results Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P < .001). The 2-year event-free survival (EFS) was similar in matched and mismatched unrelated donor and less favorable in mismatched related donor (MMRD) HSCT (P < .001). Genetic subgroups did not differ in 2-year OS (P = .1) and EFS (P = .073). In multivariate analysis, pretransplantation infections and use of MMRDs were associated with less favorable OS and EFS. With a median follow-up of 6.2 years (range, 2.0-11.8 years), 73 of 152 patients in the IR cohort were alive and well without Ig dependency. IL-2 receptor gamma chain/Janus kinase 3/IL-7 receptor–deficient SCID, myeloablative conditioning, matched donor HSCT, and naive CD4 T lymphocytes >0.5 × 10e3/μL at +1 year were identified as independent predictors of favorable clinical and immunologic outcome. Conclusion Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.
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- 2022
13. Stem Cell Transplantation for Diamond-Blackfan Anemia. A Retrospective Study on Behalf of the Severe Aplastic Anemia Working Party of the European Blood and Marrow Transplantation Group (EBMT)
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Peter Bader, Ardeshir Ghavamzadeh, Bénédicte Bruno, Akif Yeşilipek, Josu de la Fuente, Charlotte M. Niemeyer, Tatiana A Bykova, Stefano Giardino, Roland Meisel, Yasmina Mozo, Antonio M. Risitano, Jolanta Gozdzik, Ivana Bodova, Jean Hugues Dalle, Wolfgang Holter, Anne Sirvent, Henrik Sengeløv, Yves Beguin, Gergely Kriván, Miguel Pérez, Jelena Rascon, Dirk-Jan Eikema, Régis Peffault de Latour, Yves Bertrand, Maura Faraci, Marc Ansari, Vanderson Rocha, Renata Formankova, Daniela Onofrillo, Carlo Dufour, Sonia Bonanomi, Karin Mellgren, Safiatou Diallo, Matthias Wölfl, Frans J. Smiers, Andrzej Lange, Maurizio Miano, Tariq Mahmood Satti, and Paul Bosman
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medicine.medical_specialty ,Anemia ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Gastroenterology ,Bone Marrow ,Internal medicine ,medicine ,Congenital disorder ,Immunology and Allergy ,Humans ,Cumulative incidence ,Diamond–Blackfan anemia ,Child ,Diamond-Blackfan Anemia ,Anemia, Diamond-Blackfan ,Retrospective Studies ,Transplantation ,business.industry ,Hazard ratio ,Bone marrow failure ,Hematopoietic Stem Cell Transplantation ,Anemia, Aplastic ,Cell Biology ,Hematology ,medicine.disease ,Bone Marrow Failure ,surgical procedures, operative ,Cord blood ,Molecular Medicine ,business ,Stem Cell Transplantation - Abstract
Data on stem cell transplantation (SCT) for Diamond-Blackfan Anemia (DBA) is limited. We studied patients transplanted for DBA and registered in the EBMT database. Between 1985 and 2016, 106 DBA patients (median age, 6.8 years) underwent hematopoietic stem cell transplantation from matched-sibling donors (57%), unrelated donors (36%), or other related donors (7%), using marrow (68%), peripheral blood stem cells (20%), both marrow and peripheral blood stem cells (1%), or cord blood (11%). The cumulative incidence of engraftment was 86% (80% to 93%), and neutrophil recovery and platelet recovery were achieved on day +18 (range, 16 to 20) and +36 (range, 32 to 43), respectively. Three-year overall survival and event-free survival were 84% (77% to 91%) and 81% (74% to 89%), respectively. Older patients were significantly more likely to die (hazard ratio, 1.4; 95% confidence interval, 1.06 to 1.23; P < .001). Outcomes were similar between sibling compared to unrelated-donor transplants. The incidence of acute grades II to IV of graft-versus-host disease (GVHD) was 30% (21% to 39%), and the incidence of extensive chronic GVHD was 15% (7% to 22%). This study shows that SCT may represent an alternative therapeutic option for transfusion-dependent younger patients. (C) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.
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- 2021
14. Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Karl-Walter Sykora, Larysa Kostyuchenko, Jolanta Gozdzik, Bożena Dembowska-Bagińska, Peter Svec, Sara Sebnem Kilic, Barbara Pietrucha, Ewa Więsik-Szewczyk, Katarzyna Drabko, Michael H. Albert, Hanna Gregorek, Beata Wolska-Kusnierz, Barbara Piątosa, Mary Eapen, Alexandra Y. Kreins, Wojciech Młynarski, Agata Pastorczak, Krystyna H. Chrzanowska, Sylwia Kołtan, Dmitry Balashov, Agnieszka Tomaszewska, Zdenka Krenova, Monika Lejman, Natalia Miakova, Marek Ussowicz, E.V. Deripapa, Edyta Heropolitańska-Pliszka, Bendik Lund, Anna Wakulińska, Eva Hlaváčková, Johann Greil, Markus G. Seidel, Sujal Ghosh, Anna Pieczonka, Alina Fedorova, Jochen Buechner, Jan Styczyński, Krzysztof Kałwak, Wojciech Fendler, and Andrew R. Gennery
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Adult ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Comorbidity ,Kaplan-Meier Estimate ,Hematopoietic stem cell transplantation ,Malignancy ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Neoplasms ,Internal medicine ,Prevalence ,medicine ,Humans ,Child ,Nijmegen Breakage Syndrome ,Immunodeficiency ,business.industry ,Incidence ,Hematopoietic Stem Cell Transplantation ,Cancer ,medicine.disease ,3. Good health ,Natural history ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,Poland ,business ,Nijmegen breakage syndrome ,Follow-Up Studies - Abstract
Purpose: Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematologic malignancies. Experimental Design: We describe the natural history of NBS, including cancer incidence, risk of death, and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency. Results: Among 241 patients with NBS enrolled in the study from 11 countries, 151 (63.0%) patients were diagnosed with cancer. Incidence rates for primary and secondary cancer, tumor characteristics, and risk factors affecting overall survival (OS) were estimated. The cumulative cancer incidence was 40.21% ± 3.5% and 77.78% ± 3.4% at 10 years and 20 years of follow-up, respectively. Most of the tumors n = 95 (62.9%) were non-Hodgkin lymphomas. Overall, 20 (13.2%) secondary malignancies occurred at a median age of 18 (interquartile range, 13.7–21.5) years. The probability of 20-year overall survival (OS) for the whole cohort was 44.6% ± 4.5%. Patients who developed cancer had a shorter 20-year OS than those without malignancy (29.6% vs. 86.2%; P < 10−5). A total of 49 patients with NBS underwent HSCT, including 14 patients transplanted before malignancy. Patients with NBS with diagnosed cancer who received HSCT had higher 20-year OS than those who did not (42.7% vs. 30.3%; P = 0.038, respectively). In the group of patients who underwent preemptive transplantation, only 1 patient developed cancer, which is 6.7 times lower as compared with nontransplanted patients [incidence rate ratio 0.149 (95% confidence interval, 0.138–0.162); P < 0.0001]. Conclusions: There is a beneficial effect of HSCT on the long-term survival of patients with NBS transplanted in their first complete remission of cancer.
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- 2021
15. Infections with Klebsiella pneumoniae in Children Undergoing Anticancer Therapy or Hematopoietic Cell Transplantation: A Multicenter Nationwide Study
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Alicja Sękowska, Krzysztof Czyżewski, Kamila Jaremek, Patrycja Zalas-Więcek, Olga Zając-Spychała, Jacek Wachowiak, Anna Szmydki-Baran, Łukasz Hutnik, Agnieszka Gietka, Olga Gryniewicz-Kwiatkowska, Bożenna Dembowska-Bagińska, Katarzyna Semczuk, Katarzyna Dzierżanowska-Fangrat, Wojciech Czogała, Walentyna Balwierz, Iwona Żak, Renata Tomaszewska, Tomasz Szczepański, Ewa Bień, Ninela Irga-Jaworska, Katarzyna Machnik, Justyna Urbańska-Rakus, Sonia Pająk, Marcin Płonowski, Maryna Krawczuk-Rybak, Aleksandra Królak, Tomasz Ociepa, Tomasz Urasiński, Paweł Wawryków, Jarosław Peregud-Pogorzelski, Tomasz Brzeski, Katarzyna Mycko, Hanna Mańko-Glińska, Wanda Badowska, Agnieszka Urbanek-Dądela, Grażyna Karolczyk, Weronika Stolpa, Katarzyna Skowron-Kandzia, Agnieszka Mizia-Malarz, Filip Pierlejewski, Wojciech Młynarski, Jakub Musiał, Radosław Chaber, Joanna Zawitkowska, Agnieszka Zaucha-Prażmo, Katarzyna Drabko, Jolanta Goździk, Jowita Frączkiewicz, Małgorzata Salamonowicz-Bodzioch, Krzysztof Kałwak, and Jan Styczyński
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acute leukemia ,children ,hematopoietic cell transplantation ,infection ,Klebsiella pneumoniae ,Medicine - Abstract
Background: Klebsiella pneumoniae is a nosocomial pathogen that causes severe infections in immunocompromised patients. The aim of the study was to conduct a microbiological and clinical analysis of K. pneumoniae infections in children with malignancies or undergoing hematopoietic cell transplantation in Poland. Methods: We conducted a retrospective, multicenter study including children and adolescents under 19 years old treated between 2012 and 2021. We analyzed patients’ characteristics, microbiological data, and the outcomes of antibiotic therapy. Results: A total of 9121 newly diagnosed children were treated for malignancy and 1697 pediatric patients underwent hematopoietic cell transplantation. K. pneumoniae infections were diagnosed in 527 patients. Their overall incidence was 4.86% in pediatric hematology and oncology patients and 4.95% in patients who underwent hematopoietic cell transplantation. The incidence of infection was higher in patients with acute leukemia than with solid tumors (7.8% vs. 4.1%; OR = 2.0; 95% CI = 1.6–2.4; p < 0.0001). The most frequent source of infection was in the urinary tract at 55.2%. More than 57% of K. pneumoniae strains were extended-spectrum β-lactamase-positive and almost 34% were multidrug-resistant. Infections with K. pneumoniae contributed to death in 3.22% of patients. Conclusions: K. pneumoniae is one of the most critical pathogens in children suffering from malignancies or undergoing hematopoietic cell transplantation. The incidence of multidrug-resistant K. pneumoniae strains is increasing and contributing to poor clinical outcome.
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- 2024
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16. Hematopoietic cell transplantation in chronic granulomatous disease: a study of 712 children and adults
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Petr Sedlacek, Susanne Matthes, Polina Stepensky, Caroline A. Lindemans, Junfeng Wang, Jolanta Gozdzik, Manfred Hoenig, Krzysztof Kałwak, Juliana F Fernandes, Su Han Lum, Brigitte Strahm, Matthias Felber, Bénédicte Neven, Arjan C. Lankester, Amal Al Seraihy, Mervi Taskinen, Ansgar Schulz, Tayfun Güngör, Franco Locatelli, Andrew R. Gennery, Mathias Hauri-Hohl, Giovanna Lucchini, Michael H. Albert, Sheree Hazelaar, Despina Moshous, Robert Wynn, Fulvio Porta, Henric Jan Blok, Brenda Gibson, Marco Zecca, Paul Veys, Fabian Hauck, Per Ljungman, Urs Schanz, Dmitry Balashov, Serap Aksoylar, Robert Chiesa, Karl Walter Sykora, Musa Karakukcu, Mary Slatter, and Ege Üniversitesi
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Immunology ,Hematopoietic stem cell transplantation ,Disease ,Granulomatous Disease, Chronic ,Biochemistry ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Chronic granulomatous disease ,Antigen ,medicine ,Humans ,Transplantation, Homologous ,Child ,Retrospective Studies ,030304 developmental biology ,0303 health sciences ,Hematopoietic cell transplantation ,Hematopoietic cell ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Infant ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,3. Good health ,Survival Rate ,Transplantation ,surgical procedures, operative ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Child, Preschool ,Primary immunodeficiency ,Female ,business ,Follow-Up Studies ,030215 immunology - Abstract
Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can cure the disease, but the indication to transplant remains controversial. We performed a retrospective multicenter study of 712 patients with CGD who underwent allo-HCT transplantation from March 1993 through December 2018. We studied 635 children (aged 1 antigen mismatch. Choice of conditioning regimen did not influence OS or EFS. In summary, we report an excellent outcome after allo-HCT in CGD, with low incidence of graft failure and mortality in all ages. Older patients and recipients of 1-antigen-mismatched grafts had a less favorable outcome. Transplantation should be strongly considered at a younger age and particularly in the presence of a well-matched donor.
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- 2020
17. Disseminated Juvenile Xanthogranuloma and Hemophagocytic Lymphohistiocytosis Developed During Treatment of Acute Lymphoblastic Leukemia: Case Report
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Elżbieta Wyrobek, Magdalena Ćwiklińska, Jolanta Gozdzik, Karolina Bukowska-Strakova, Szymon Skoczeń, Agnieszka Dluzniewska, Katarzyna Pawińska-Wa Sikowska, Monika Rygielska, Konrad Stepien, Walentyna Balwierz, and Grazyna Drabik
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0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Juvenile xanthogranuloma ,medicine.medical_treatment ,juvenile xanthogranuloma ,Hematopoietic stem cell transplantation ,acute lymphoblastic leukemia ,lcsh:RC254-282 ,03 medical and health sciences ,chemistry.chemical_compound ,Non-Langerhans cell histiocytosis ,0302 clinical medicine ,Tocilizumab ,hemic and lymphatic diseases ,medicine ,case report ,Histiocyte ,Hemophagocytic lymphohistiocytosis ,business.industry ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Histiocytosis ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Oncology ,hemophagocytic lymphohistiocytosis ,030220 oncology & carcinogenesis ,non-Langerhans cell histiocytosis ,Bone marrow ,business - Abstract
The association between acute lymphoblastic leukemia (ALL), non-Langerhans cell histiocytosis (non-LCH), and hemophagocytic lymphohistiocytosis (HLH), to the best of our knowledge, has not been published to date. Juvenile xanthogranuloma (JXG), as a type of non-LCH, is usually a benign disease limited to the skin. Systemic involvement is rarely reported. The present case report describes a 15-year-old boy diagnosed with disseminated JXG involving skin and bone marrow concurrent with severe symptoms of HLH during ALL therapy. Examination of immunoglobulin heavy chain genes in B-cell precursor leukemic blasts and histiocytes in the skin and bone marrow revealed identical rearrangements, confirming clonal relationship between both diseases. Implementation of corticosteroids, vinblastine, etoposide, cyclosporine, and tocilizumab resulted in partial skin lesion resolution with no improvement of bone marrow function; therefore, hematopoietic stem cell transplantation (HSCT) was eventually performed. The patient's hematological and general status has improved gradually; however, remarkable recovery of skin lesions was observed after empirical antitubercular therapy. Mycobacterium spp. infection should be considered as a possible secondary HLH trigger. Triple association of ALL, non-LCH, and HLH highlights heterogeneity of histiocytic disorders and possible common origin of dendritic and lymphoid cells.
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- 2020
18. Treosulfan-fludarabine-thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies
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Klaus Daniel Stachel, Katarzyna Drabko, Petr Sedlacek, Bernd Gruhn, Selim Corbacioglu, Jolanta Gozdzik, Krzysztof Kałwak, Peter Bader, Katharine Patrick, Franco Locatelli, Claudia Hemmelmann, Franca Fagioli, Joachim Baumgart, Paul G. Schlegel, Rita Beier, Jan Styczyński, Ann Kristin Möller, Johann Greil, Birgit Burkhardt, Ajay Vora, Karl Walter Sykora, Ingo Müller, and Monika Mielcarek
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Male ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Medizin ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,ThioTEPA ,Treosulfan ,hematopoietic stem cell transplantation ,children ,hematologic neoplasms ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Leukaemia ,Cumulative incidence ,Child ,Busulfan ,Transplantation ,Juvenile myelomonocytic leukemia ,business.industry ,Haematopoietic stem cells ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,medicine.disease ,Fludarabine ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,HSCT ,Female ,business ,Thiotepa ,Vidarabine ,030215 immunology ,medicine.drug - Abstract
Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m2/day (7.7%), 12 g/m2/day (35.4%), or 14 g/m2/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I–IV and 26.6% for grades II–IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies.
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- 2020
19. HLA-inferred extended haplotype disparity level is more relevant than the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor
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Elżbieta Graczyk-Pol, Anna Lojko-Dankowska, Jolanta Gozdzik, Anna Koclęga, Agnieszka Tomaszewska, Beata Wójcik, Joanna Dziopa, M. Barańska, Mieczysław Komarnicki, Jacek Nowak, Marta Zubala, Sebastian Giebel, Jacek Wachowiak, Slawomira Kyrcz-Krzemien, Kazimierz Hałaburda, Jerzy Kowalczyk, Andrzej Hellmann, Tomasz Czerw, Agnieszka Witkowska, Krzysztof Kałwak, Maria Bieniaszewska, Lidia Gil, Anna Pieczonka, Andrzej Szczepiński, Urszula Szlendak, Slawomir Gwozdowicz, Sylwia Madej, Marta Rogatko-Koros, Jan Styczyński, Renata Mika-Witkowska, Anna Czyż, Barbara Nasiłowska-Adamska, Agnieszka Gawron, Miroslaw Markiewicz, Monika Mielcarek, Krzysztof Warzocha, Kazimierz Kuliczkowski, Mariusz Wysocki, Jarosław Dybko, Agnieszka Kucharska, Daria Pawliczak, Emilia Jaskula, Jerzy Holowiecki, Andrzej Lange, Katarzyna Koscinska, Klaudia Nestorowicz, Anna Gronkowska, Wiesław Wiktor Jędrzejczak, and Katarzyna Drabko
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Male ,0301 basic medicine ,Isoantigens ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,0302 clinical medicine ,HLA Antigens ,Immunology and Allergy ,Child ,education.field_of_study ,biology ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Middle Aged ,Prognosis ,Treatment Outcome ,surgical procedures, operative ,medicine.anatomical_structure ,Child, Preschool ,Hematologic Neoplasms ,Histocompatibility ,Female ,Adult ,Adolescent ,T cell ,Immunology ,Population ,Human leukocyte antigen ,Major histocompatibility complex ,Young Adult ,03 medical and health sciences ,medicine ,Humans ,education ,Alleles ,Polymorphism, Genetic ,business.industry ,Haplotype ,Infant ,medicine.disease ,Survival Analysis ,HLA Mismatch ,030104 developmental biology ,Graft-versus-host disease ,Haplotypes ,biology.protein ,business ,030215 immunology - Abstract
Serious risks in unrelated hematopoietic stem cell transplantation (HSCT) including graft versus host disease (GvHD) and mortality are associated with HLA disparity between donor and recipient. The increased risks might be dependent on disparity in not-routinely-tested multiple polymorphisms in genetically dense MHC region, being organized in combinations of two extended MHC haplotypes (Ehp). We assessed the clinical role of donor-recipient Ehp disparity levels in N = 889 patients by the population-based detection of HLA allele phase mismatch. We found increased GvHD incidences and mortality rates with increasing Ehp mismatch level even with the same HLA mismatch level. In multivariate analysis HLA mismatch levels were excluded from models and Ehp disparity level remained independent prognostic factor for high grade acute GvHD (p = 0.000037, HR = 10.68, 95%CI 5.50-32.5) and extended chronic GvHD (p 0.000001, HR = 15.51, CI95% 5.36-44.8). In group with single HLA mismatch, patients with double Ehp disparity had worse 5-year overall survival (45% vs. 56%, p = 0.00065, HR = 4.05, CI95% 1.69-9.71) and non-relapse mortality (40% vs. 31%, p = 0.00037, HR = 5.63, CI95% 2.04-15.5) than patients with single Ehp disparity. We conclude that Ehp-linked factors contribute to the high morbidity and mortality in recipients given HLA-mismatched unrelated transplant and Ehp matching should be considered in clinical HSCT.
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- 2018
20. Mesenchymal Stem Cells as a Salvage Treatment for Severe Refractory Graft-vs-Host Disease in Children After Bone Marrow Transplantation
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Marcin Majka, Wojciech Czogała, Magdalena Wozniak, Jolanta Gozdzik, A. Dluzniewska, Szymon Skoczeń, Oktawiusz Wiecha, Danuta Jarocha, and Aleksandra Krasowska-Kwiecień
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Disease ,Hematopoietic stem cell transplantation ,Mesenchymal Stem Cell Transplantation ,Gastroenterology ,Refractory ,Internal medicine ,medicine ,Humans ,Child ,Bone Marrow Transplantation ,Salvage Therapy ,Transplantation ,business.industry ,Remission Induction ,Mesenchymal stem cell ,Hematopoietic Stem Cell Transplantation ,Immunosuppression ,Overlap syndrome ,medicine.disease ,Haematopoiesis ,Child, Preschool ,Female ,Surgery ,business - Abstract
Application of mesenchymal stem cells (MSC) enables a novel approach to the therapy of graft- vs-host disease (GVHD) after hematopoietic stem cell transplantation. Herein we present our preliminary experience with the use of allogeneic bone marrow‒derived MSC in 9 pediatric patients after hematopoietic transplantation complicated by severe acute or chronic GVHD (aGVHD, cGVHD) resistant to steroids and second-line immunosuppressants. The MSC therapy was applied concurrently with immunosuppressive treatment in 5 patients as a single infusion, in four patients as 2-6 infusions. The median dose of cells per infusion was 1.9 × 106/kg of recipient body weight (range, 0.1–6.5 × 106/kg). The median quantity of cells applied to patients was 1.2 × 106/kg (range, 0.2–30.9 × 106/kg). We did not observe any adverse symptoms of MSC therapy. Overall, partial, or complete remission (PR and CR, respectively) was obtained in 56% of patients after the first MSC infusions, and 44% after completing therapy. In those with skin involvement 50% achieved permanent CR, 38% in those with gastrointestinal manifestations, and 33% in those with liver GVHD. Three patients with overlap syndrome had amelioration, but none had permanent remission. Long-term improvement after consecutive MSC doses was observed in 3 patients. In the 4- to 8-year follow-up, 3 patients are alive and 2 have attained permanent remission. Six patients died during follow-up: 4 with aGVHD and 2 with infectous complications. Co-treatment of streoid-resistant GVHD with MSC and conventional immunosuppression can improve the outcome, although therapy regimens remain to be established.
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- 2019
21. Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adults with Chronic Granulomatous Disease (CGD): A Study of the Inborn Errors Working Party (IEWP) of the EBMT
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Jolanta Gozdzik, Caroline A. Lindemans, Urs Schanz, Manfred Hoenig, Karl-Walter Sykora, Robert Chiesa, Benedicte Neven, Petr Sedlacek, Franco Locatelli, Henric-Jan Blok, Mary Slatter, Polina Stepensky, Michael H. Albert, Ansgar Schulz, Matthias Felber, Amal Al-Seraihy, Serap Aksoylar, Krzysztof Kałwak, Arjan C. Lankester, Marco Zecca, Andrew R. Gennery, Brigitte Strahm, Paul Veys, Fabian Hauck, Per Ljungman, Robert Wynn, Su Han Lum, Despina Moshous, Junfeng Wang, and Tayfun Guengoer
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medicine.medical_specialty ,business.industry ,Surrogate endpoint ,Proportional hazards model ,medicine.medical_treatment ,Incidence (epidemiology) ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,ThioTEPA ,030204 cardiovascular system & hematology ,medicine.disease ,Biochemistry ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,Graft-versus-host disease ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Cumulative incidence ,business ,medicine.drug - Abstract
Introduction: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by impairment of the phagocyte NADPH-oxidase complex, resulting in deficient microbial killing and life-threatening bacterial and fungal infections. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative approach, but it can be complicated by graft failure, graft versus-host disease (GvHD) and transplant-related mortality (TRM). In order to define prognostic risk factors in this setting, the IEWP of the EBMT performed a large retrospective registry study on 600 pediatric and adult patients with CGD undergoing allo-HSCT. Patients and Methods: We analyzed the outcome of patients with CGD who received allo-HSCT in EBMT centers between 1993 and 2017. The main end-points of the study were overall survival (OS) and event-free survival (EFS; events were death and primary or secondary engraftment failure) according to patient's age, donor type, stem cell source and conditioning regimen. One patient died before allo-HSCT and was excluded from analysis. Results: We studied 536 children (aged < 18 years) and 63 adults (aged ≥ 18 years) affected by CGD. The median follow-up was 45.37 months (IQR 15.8-81.8). Genetic results were available for 307 patients: inheritance was X-linked (75%) or autosomal recessive (25%). Median age at transplant was 7.2 years (range: 0.12-48.56). Conditioning regimen was Busulfan/Fludarabine (n=244; 41%), Busulfan/Cyclophosphamide (n=104; 17%), Treosulfan/Fludarabine (n=76; 13%), Treosulfan/Fludarabine/Thiotepa (n=52; 9%) or other drug combinations (n=123; 20%). Donors were human leukocyte antigen (HLA) matched related (MFD, 10/10; n=211, 40%), matched unrelated (MUD, 10/10 or 6/6 in UCB; n=201; 38%), mismatched related (MMFD, ≥ 9/10; n= 27; 5%) or mismatched unrelated (MMUD, ≥ 9/10 or 5/6 in UCB; n= 83; 16%). Stem cell source was bone marrow (BM; n=408; 69%), peripheral blood (PB; n=153; 26%) or umbilical cord blood (UCB; n=27; 5%). Donor engraftment occurred in 516 evaluable patients (88%), while primary or secondary engraftment failure occurred in 68 patients (12%). Seventy-nine patients (13%) died after allo-HSCT. The 2 year Kaplan-Meier estimate of OS and EFS were 87.1% (95% CI, 84.2-89.9) and 77.8% (95% CI, 74.2-81.4), respectively (Fig A). The 2-year cumulative incidence of grade II-IV acute GvHD, chronic GvHD and extensive chronic GvHD was 18.6% (95%, 15.1-22.2), 16.2 % (95%, 18.8-19.7) and 5.5% (95%, 3.4-7.7), respectively. A univariate cox model with spline term demonstrated that older age at transplant was associated with an increased risk of death (p=0.002). Children undergoing allo-HSCT had a superior 2y OS (88.1%; 95% CI 85.2-91.0), compared to adults (78.2%; 95% CI, 67.7-88.7), p=0.03 (Fig B). Patients undergoing allo-HSCT from a MFD had a superior EFS (86.5%; 95% CI 81.5-91.4) compared to MUD (73.3%; 95% CI 66.7-79.9), MMUD (78.2%; 95% CI 69-87.5) and MMFD (59.7; 95% CI 40.4-79.1), p< 0.001 (Fig C). Patients receiving BM grafts had superior 2y EFS (81.0%; 95% CI 76.9-85.1) compared to PB (72.5%; 95% CI 64.7-80.4) and UCB (66.7%; 95% CI 48.9-84.4), p=0.04. The pattern of disease inheritance and the choice of conditioning regimen didn't have an impact on outcome (Fig D). Fifty-three patients with graft failure underwent a second allo-HSCT and the 2y OS in this group was 82.1% (95% CI, 71.5-92.7). Year of transplantation didn't have an influence on outcome. Conclusion: This is the largest study describing the outcome of allo-HSCT in children and adults affected by CGD. We demonstrate an excellent outcome, with a low incidence of graft failure, TRM and GvHD. Older patients with CGD have reduced survival after allo-HSCT, indicating that transplant should be considered at a younger age. The use of a MMFD is associated with poorer outcome; indication to transplant in this setting should be carefully evaluated by the treating physicians. Disclosures Chiesa: Bluebird Bio: Consultancy; Gilead: Consultancy. Kalwak:medac: Other: travel grants; Sanofi: Other: travel grants. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Locatelli:Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; bluebird bio: Consultancy; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wynn:Orchard SAB: Membership on an entity's Board of Directors or advisory committees; Orchard Therapeutics: Equity Ownership; Chimerix: Research Funding; Genzyme: Honoraria; Bluebird Bio: Consultancy; Orchard Therapeutics: Consultancy; Chimerix: Consultancy. Zecca:Chimerix: Honoraria. Veys:Pfizer: Honoraria; Servier: Research Funding; Novartis: Honoraria. Slatter:Medac: Other: Travel assistance.
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- 2018
22. Low seroprevalence and low incidence of infection with Toxoplasma gondii (Nicolle et Manceaux, 1908) in pediatric hematopoietic cell transplantation donors and recipients: Polish nationwide study
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Małgorzata Salamonowicz, Jolanta Gozdzik, Agnieszka Zaucha-Prażmo, Jowita Fraczkiewicz, Krzysztof Czyżewski, Olga Zajac-Spychala, Anna Pieczonka, and Jan Styczyński
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,030231 tropical medicine ,030308 mycology & parasitology ,Serology ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,immune system diseases ,Seroepidemiologic Studies ,hemic and lymphatic diseases ,Internal medicine ,parasitic diseases ,Epidemiology ,medicine ,Prevalence ,Seroprevalence ,Humans ,Child ,Taxonomy ,Retrospective Studies ,0303 health sciences ,biology ,Incidence (epidemiology) ,Incidence ,Hematopoietic Stem Cell Transplantation ,Toxoplasma gondii ,Infant ,Retrospective cohort study ,Biodiversity ,Middle Aged ,medicine.disease ,biology.organism_classification ,Toxoplasmosis ,Tissue Donors ,Transplantation ,surgical procedures, operative ,Child, Preschool ,Parasitology ,Female ,Poland ,Toxoplasma - Abstract
Toxoplasmosis is a potentially fatal complication after hematopoietic cell transplantation (HCT). Pre-transplant seropositivity of graft recipient to Toxoplasma gondii (Nicolle et Manceaux, 1908) is an important factor for disease reactivation after HCT. As toxoplasmosis epidemiology varies all over the world, we performed a Polish nationwide retrospective cohort study to determine the seroprevalence of toxoplasmosis in donors and pediatric allogeneic and autologous HCT recipients and the incidence of clinically evident toxoplasmosis in this patient group. Polish adult donors had higher anti-T. gondii seroprevalence than Polish pediatric donors (28% vs 8%; OR = 4.4; p = 0.02) and allo-HCT recipients (28% vs 17%; OR = 1.9; p = 0.01). Clinically apparent disease occurred in 1% of allo-HCT recipients: it was diagnosed by PCR as cerebral and/or ocular toxoplasmosis and successfully treated with antiprotozoal therapy. Regarding current practice, no prospective screening for infection of T. gondii in pediatric HCT centres is being performed, but, vast majority of HCT pediatric patients are receiving anti-T. gondii active prophylaxis. Since pre-HCT T. gondii serology was not assessed in all HCT; recipients, we propose this test should be a standard practice. Standardisation of management with infection of T. gondii in children after HCT is needed.
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- 2018
23. Stem Cell Transplantation for Diamond-Blackfan Anemia. a Retrospective Study on Behalf of Severe Aplastic Anemia Working Party of the European Blood and Marrow Transplantation Group (EBMT)
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Yves Bertrand, Akif Yeşilipek, Vanderson Rocha, Tatiana A Bykova, Paul Bosman, Tariq Mahmood Satti, Antonio M. Risitano, Jolanta Gozdzik, Miguel Pérez, Yasmina Mozo, Ardeshir Ghavamzadeh, Gergely Kriván, Carlo Dufour, Dirk-Jan Eikema, Andrzej Lange, Régis Peffault de Latour, Josu de la Fuente, Henrik Sengeløv, Edoardo Lanino, Bénédicte Bruno, Jelena Rascon, Anne Sirvent, Renata Formankova, Matthias Wölfl, Yves Beguin, Karin Mellgren, Maurizio Miano, Charlotte M. Niemeyer, Marc Ansari, Frans J. Smiers, Peter Bader, Ivana Bodova, Attilio Rovelli, Roland Meisel, Dominique Bron, and Daniela Onofrillo
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medicine.medical_specialty ,business.industry ,Marrow transplantation ,medicine.medical_treatment ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,medicine.disease ,Biochemistry ,Severe Aplastic Anemia ,Transplantation ,Regimen ,Family medicine ,medicine ,Aplastic anemia ,Diamond–Blackfan anemia ,business ,health care economics and organizations - Abstract
INTRODUCTION Diamond-Blackfan Anemia (DBA) is a congenital pure red cell aplasia, secondary to ribosomal protein genetic defects that usually presents within the first year of age and can be associated with congenital abnormalities and increased risk of cancer. Some patients are successfully treated with steroids but most of them remain transfusion-dependent. Stem Cell Transplantation (SCT) represents the only curative option for this disease, however data from literature is scarce and limited to a very small number of cases. In this retrospective study we describe the outcome of SCT in patients with DBA reported in the EBMT data base. PATIENTS AND METHODS The study was conducted on behalf of Severe Aplastic Anemia Working Party of the EBMT and was based on data of patients affected with DBA who underwent SCT and registered in the EBMT Data Base. Clinical information of the disease and details on transplant procedures and follow-up were collected by a specific form distributed to Centres participating in the study. RESULTS Between 1985-2016, 106 patients (60 males-46 females) aged 6.8 yo (range 1-32) underwent SCT from matched sibling donor (58, 57%), unrelated donor (37, 36%) or from other donors (7, 7%) using bone marrow (73, 69%), peripheral blood (21, 20%) or cord blood (12, 11%) as cell source. 91 patients (86%) received a myeloblative regimen which included Busulfan in 66 cases. 86% (80-93%) of patients engrafted by day 28. Median days to neutrophils and platelets engraftment were 18 and 36, respectively. EFS and OS at 36 months were 81% (74-89%) and 84% (77-91%), respectively. OS was significantly higher (p=0.01) in patients CONCLUSION To the best of our knowledge, this is the largest reported cohort of patients transplanted for DBA and having a long follow-up. The very good OS of patients undergoing transplant from both sibling and unrelated donors and the rather low rate of cGvHD confirms that this procedure can be considered an alternative option for transfusion-dependent patients Disclosures Bader: Riemser, Neovii: Research Funding; Medac: Patents & Royalties, Research Funding; Amgen (Brasil), Novartis: Consultancy, Speakers Bureau; Celgene: Consultancy. Risitano:Alexion: Honoraria, Research Funding, Speakers Bureau; Achillion: Research Funding; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biocryst: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Research Funding, Speakers Bureau; Amyndas: Consultancy; Samsung: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amyndas: Consultancy; Biocryst: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ra Pharma: Research Funding; Ra Pharma: Research Funding; Alnylam: Research Funding; Alnylam: Research Funding; Achillion: Research Funding. Peffault de Latour:Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding.
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- 2019
24. Physicians Abstracts
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Yves Bertrand, Elena Soncini, A.C. Lankester, Iewp Ebmt, Francesca Ferrua, K. Kałwak, Manfred Hönig, Jolanta Gozdzik, B Al-Saud, EG Davies, Hamoud Al-Mousa, Benedicte Neven, Courteille, SJ Keogh, Gergely Kriván, Andrew R. Gennery, W Czogala, Per Ljungman, Michael H. Albert, Renata Formankova, Nizar Mahlaoui, Andrzej Lange, Claire Booth, Ales Janda, Dmitry Balashov, Isabelle Meyts, Mary Slatter, Bordon, A Fischer, Anders Fasth, Felipe Suarez, Aydan Ikinciogullari, Carsten Heilmann, and Figen Dogu
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Transplantation ,Haematopoiesis ,business.industry ,Cancer research ,Medicine ,Hematology ,CD40 Ligand Deficiency ,Stem cell ,business ,Article - Published
- 2015
25. Analysis of Risk Factors Determining Incidence and Outcome of Infections in Children and Adults after Hematopoietic Cell Transplantation
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Agnieszka Wierzbowska, Manko Joanna, Jacek Wachowiak, Sebastian Giebel, Monika Adamska, Grzegorz W. Basak, Jan Styczyński, Jolanta Gozdzik, Monika Biernat, Patrycja Mensah-Glanowska, Agnieszka Zaucha-Prażmo, Alicja Sadowska-Klasa, Jarosław Dybko, Lidia Gil, Jowita Fraczkiewicz, Mariusz Wysocki, Joanna Drozd-Sokołowska, Slawomira Kyrcz-Krzemien, Anna Waszczuk-Gajda, Jerzy Kowalczyk, Piotr Rzepecki, Agnieszka Piekarska, Olga Zajac-Spychala, Krzysztof Kałwak, Agnieszka Tomaszewska, Małgorzata Salamonowicz, Krzysztof Czyżewski, Kazimierz Hałaburda, and Marek Hus
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medicine.medical_specialty ,Acute leukemia ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Cmv reactivation ,medicine.disease ,Logistic regression ,Biochemistry ,Transplantation ,Internal medicine ,Relative risk ,Medicine ,business ,Multiple myeloma - Abstract
BACKGROUND: Recent EBMT analysis showed that infections are responsible for 21% of deaths after allo-HCT and 11% after auto-HCT. However, the risk, types and outcome of infections vary between age groups. The aim of the study is the direct comparison of risk factors of incidence and outcome of infections in children and adults. PATIENTS AND METHODS: We analyzed risk factors for the incidence and outcome of bacterial, fungal, and viral infections in 650 children and 3200 adults who received HCT between 2012-2015. The risk factors were determined by multivariable logistic regression analysis. RESULTS: A total number of 395/650 (60.8%) children and 1122/3200 (35.0%) adults were diagnosed for microbiologically confirmed infection, including 345/499 (69.1%) and 679/1070 (63.5%), respectively after allo-HCT, and 50/151 (33.1%) and 443/2130 (20.8%) respectively, after auto-HCT. At 2 years after HCT, the incidences of microbiologically documented bacterial infection were 36.0% and 27.6%, (p21d) hematological recovery (HR=3.3; p21 days (HR=1.4; p=0.038) were associated with increased risk of death from infection. Among patients with bacterial infections, the risk was higher in G- infections (HR=1.6; p=0.031). Among auto-HCT patients, no child died of infection. In adults, the risk of death was higher if duration of treatment of infection was >21 days (HR=1.7; p CONCLUSIONS: The profile of infections and related deaths varies between children and adults. MMUD transplants, diagnosis of acute leukemia, chronic GVHD, CMV reactivation and prolonged infection are relative risk factors for death from infection after HCT. Disclosures Kalwak: Sanofi: Other: travel grants; medac: Other: travel grants.
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- 2018
26. Interactions of monocyte subpopulations generated from cord blood CD34+ hematopoietic progenitors with tumor cells: Assessment of antitumor potential
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Jarosław Baran, Monika Baj-Krzyworzeka, Bozenna Mytar, Jolanta Gozdzik, Marek Zembala, Rafał Szatanek, Małgorzata Stec, and Maciej Siedlar
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Cancer Research ,CD14 ,CD34 ,Mice, SCID ,CD16 ,Biology ,Monocytes ,Immunophenotyping ,Mice ,Mice, Inbred NOD ,Genetics ,medicine ,Animals ,Humans ,Progenitor cell ,Molecular Biology ,Monocyte ,Cell Biology ,Hematology ,Fetal Blood ,Hematopoietic Stem Cells ,Haematopoiesis ,medicine.anatomical_structure ,Cord blood ,Immunology ,Cancer research - Abstract
Monocytes and their subsets (CD14(++)CD16(+) and CD14(+)CD16(-)) generated from cord blood CD34(+) progenitor cells were used for determination of their capacity to interact with tumor cells in vitro and in vivo. The studies in vitro included adhesion to human umbilical vein endothelial cells, cytotoxicity, production of toxic mediators: reactive oxygen and nitrogen intermediates (ROI and RNI, respectively), and finally their effect on transplantable human tumor growth in nonobese diabetic severe combined immunodeficient mice. The CD14(++)CD16(+) subset exhibited an increased adherence to human umbilical vein endothelial cells and cytotoxicity toward tumor cells in vitro. CD14(+)CD16(-) monocytes showed a higher production of reactive oxygen and nitrogen intermediates after stimulation with tumor cells, and more pronounced inhibition of tumor growth in vivo. The results revealed significant differences in the behavior of CD14(++)CD16(+) and CD14(+)CD16(-) monocyte subsets toward tumor cells, thus providing further evidence that CD34(+) cell-derived monocytes differ in this respect from blood monocytes. The protocol for generation of monocytes with antitumor reactivity described here may be useful to obtain monocytes from CD34(+) progenitor cells of cancer patients. This might offer a basis for a novel approach for various forms of cellular immunotherapy of cancer.
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- 2012
27. Molecular Identification of Extrapulmonary Vaccine Adverse Events after BCG in Paraffin-Embedded Specimens
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Sylwia Brzezińska, Anna Zabost, Dagmara Borkowska-Tatar, Magdalena Klatt, Jolanta Goździk, Agnieszka Dłużniewska, Katarzyna Błasińska, and Ewa Augustynowicz-Kopeć
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Mycobacterium bovis BCG ,genetic test ,granulomas ,histopathological specimens ,Medicine - Abstract
According to the World Health Organization (WHO), around 1 million children worldwide are diagnosed with tuberculosis each year. The Bacillus Calmette–Guérin (BCG) vaccine has been used around the world for over 100 years. The complications of the BCG vaccination can occur in about 0,06% of children and include local or systemic adverse reactions. Due to the close analogy between the vaccine strain and other species of the Mycobacterium tuberculosis complex (MTBC), molecular methods are recommended for differential diagnosis of Vaccine adverse events (VAE) after BCG. The ability to quickly and specifically identify BCG is important in view of different treatment regimens. The aim of the study was to assess the usefulness of genetic testing for Mycobacterium bovis BCG in the paraffin-embedded specimens’ methods. We describe two cases of VAE in immune-compromised children presenting with osteoarticular changes that had been clinically suspected of tuberculosis and led to molecular identification through GeneXpert, GenoType MTBC, and Spoligotyping. Results: Mycobacterium bovis BCG was detected in osteoarticular changes embedded in paraffin block of two patients. Conclusion: Genetic tests using paraffin-embedded materials allow for quick identification and differential diagnosis of patients with Tuberculosis and VAE after BCG. This is an important issue, especially in cases where the tissue has only been submitted for histopathological examination without microbiological diagnostics for tuberculosis.
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- 2023
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28. Micafungin in invasive fungal infections in children with acute leukemia or undergoing stem cell transplantation
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Małgorzata Salamonowicz, Tomasz Urasiński, Weronika Stolpa, Wanda Badowska, Michał Matysiak, Grazyna Sobol, Jowita Frackiewicz, Lukasz Hutnik, Mariusz Wysocki, Krzysztof Kałwak, Lidia Gil, Bożenna Dembowska-Bagińska, Krzysztof Czyżewski, Mariola Woszczyk, Jacek Wachowiak, Jolanta Gozdzik, Karolina Siewiera, Grażyna Karolczyk, Agnieszka Kolodziejczyk-Gietka, Tomasz Ociepa, Jan Styczyński, Danuta Perek, Agnieszka Urbanek-Dadela, Olga Gryniewicz-Kwiatkowska, Zuzanna Gamrot, Olga Zajac-Spychala, and Zofia Małas
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Antifungal Agents ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,030106 microbiology ,Targeted therapy ,03 medical and health sciences ,Echinocandins ,Immunocompromised Host ,Lipopeptides ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Child ,Retrospective Studies ,Acute leukemia ,Leukemia ,business.industry ,Micafungin ,Infant, Newborn ,Infant ,Hematology ,medicine.disease ,Transplantation ,Haematopoiesis ,Treatment Outcome ,030220 oncology & carcinogenesis ,Child, Preschool ,Acute Disease ,Female ,Stem cell ,business ,Invasive Fungal Infections ,medicine.drug ,Stem Cell Transplantation - Abstract
This analysis shows that the use of micafungin was successful in preemptive and targeted therapy in children with IFD in 85% pediatric hemato-oncology (PHO) and 60% allogeneic hematopoietic stem ce...
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- 2016
29. Rapid full engraftment and successful immune reconstitution after allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in Omenn syndrome
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Anna Mordel, Marcin Majka, Ewa Lesko, Wojciech Czogała, Danuta Kowalczyk, Marek Zembala, Oktawiusz Wiecha, Szymon Skoczeń, Aleksandra Krasowska-Kwiecień, and Jolanta Gozdzik
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Male ,Human cytomegalovirus ,Transplantation Conditioning ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Antiviral Agents ,hemic and lymphatic diseases ,medicine ,Humans ,Transplantation, Homologous ,Eosinophilia ,Lymphocytes ,Bone Marrow Transplantation ,Transplantation ,Severe combined immunodeficiency ,business.industry ,Siblings ,Hematopoietic Stem Cell Transplantation ,Infant ,medicine.disease ,Omenn syndrome ,Treatment Outcome ,surgical procedures, operative ,medicine.anatomical_structure ,Immune System ,Cytomegalovirus Infections ,Pediatrics, Perinatology and Child Health ,Immunology ,Severe Combined Immunodeficiency ,Bone marrow ,Stem cell ,medicine.symptom ,business ,Immunosuppressive Agents - Abstract
OS is a variant of SCID characterized by generalized erythroderma, alopecia, eosinophilia, and elevated IgE levels. It is fatal unless treated with allogeneic HSCT, which is the only curative approach. However, treatment related complications and graft rejection are major obstacles to the success of treatment. In this report, we describe a patient with OS, complicated by prolonged cytomegalovirus infection, successfully treated by reduced intensity conditioning allogeneic HSCT from sibling donor.
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- 2009
30. National experience with adenosine deaminase deficiency related SCID in Polish children
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Nel Dąbrowska-Leonik, Barbara Piątosa, Ewa Słomińska, Nadezda Bohynikova, Katarzyna Bernat-Sitarz, Ewa Bernatowska, Beata Wolska-Kuśnierz, Krzysztof Kałwak, Sylwia Kołtan, Anna Dąbrowska, Jolanta Goździk, Marek Ussowicz, and Małgorzata Pac
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adenosine deaminase (ADA) deficiency ,SCID - severe combined immunodeficiency ,ERT (enzyme replacement therapy) ,HSCT = hematopoietic stem cell transplant ,lymphopenia ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionDeficiency of adenosine deaminase (ADA) manifests as severe combined immunodeficiency (SCID), caused by accumulation of toxic purine degradation by-products. Untreated patients develop immune and non-immune symptoms with fatal clinical course. According to ESID and EBMT recommendations enzyme replacement therapy (ERT) should be implemented as soon as possible to stabilize the patient’s general condition, normalize transaminases, treat pulmonary proteinosis, bone dysplasia, and protect from neurological damage. Hematopoietic stem cell transplantation (HSCT) from a matched related donor (MRD) is a treatment of choice. In absence of such donor, gene therapy (GT) should be considered. HSCT from a matched unrelated donor (MUD) and haploidentical hematopoietic stem cell transplantation (hHSCT) are associated with worse prognosis.Material and methodsWe retrospectively evaluated the clinical course and results of biochemical, immunological and genetic tests of 7 patients diagnosed in Poland with ADA deficiency since 2010 to 2022.ResultsAll patients demonstrated lymphopenia affecting of T, B and NK cells. Diagnosis was made on the basis of ADA activity in red blood cells and/or genetic testing. Patients manifested with various non-immunological symptoms including: lung proteinosis, skeletal dysplasia, liver dysfunction, atypical hemolytic-uremic syndrome, and psychomotor development disorders. Five patients underwent successful HSCT: 3 patients from matched unrelated donor, 2 from matched sibling donor, and 1 haploidentical from a parental donor. In 4 patients HSCT was preceded by enzyme therapy (lasting from 2 to 5 months). One patient with multiple organ failure died shortly after admission, before the diagnosis was confirmed. None of the patients had undergone gene therapy.ConclusionsIt is important to diagnose ADA SCID as early as possible, before irreversible multi-organ failure occurs. In Poland HSCT are performed according to international immunological societies recommendations, while ERT and GT are less accessible. Implementation of Newborn Screening (NBS) for SCID in Poland could enable recognition of SCID, including ADA-SCID.
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- 2023
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31. Treatment for primary refractory Hodgkin's disease: a comparison of high-dose chemotherapy followed by ASCT with conventional therapy
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Piotr Smolewski, Jerzy Holowiecki, Wanda Knopinska-Posluszny, Jolanta Gozdzik, Arnon Nagler, T. Zemelka, L. Kachel, Andrzej Hellmann, Tadeusz Robak, W.W. Jędrzejczak, Marek Z. Wojtukiewicz, M. Pawlicki, Richard Szydlo, Michal Osowiecki, Jan Walewski, Grzegorz Charliński, Jaroslaw Czyz, Z. Sawicki, Abraham Avigdor, and J. Hansz
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Disease ,Gastroenterology ,High dose chemotherapy ,Autologous stem-cell transplantation ,Refractory ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Child ,Bone Marrow Transplantation ,Retrospective Studies ,Salvage Therapy ,Transplantation ,Chemotherapy ,Univariate analysis ,business.industry ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Hodgkin Disease ,Survival Analysis ,Lymphoma ,Surgery ,Multivariate Analysis ,Refractory Hodgkin's Disease ,Female ,business - Abstract
Our previously published study showed promising results of autologous stem cell transplantation (ASCT) in patients with primary resistant Hodgkin's disease (HD). Probabilities of overall survival (OS) and progression-free survival (PFS) at 3 years were 55 and 36%, respectively. The present study was undertaken to compare these results with conventionally treated patients and thus evaluate therapeutic options. Retrospective data on 76 adult patients who underwent ASCT were matched with 76 conventionally treated patients from 17 centers. Comparison of clinical characteristics in both groups showed that ASCT patients were younger (24 vs 31.5 years, P=0.001), more frequently presented with 'B' symptoms (P=0.03) and that more patients treated with chemotherapy (CT) had elevated LDH (P=0.03). In univariate analyses, bulky disease (P=0.0043) and complete resistance to standard CT (P=0.051) were found to be risk factors for OS. In a multivariate survival analysis only bulky disease was found to an independent prognostic factor (P=0.005). There was no difference in survival between the treatment groups with 5 years OS 33.7 (CI: 23-46) in the ASCT group and 35.6% (CI: 25-50) for the CT group (P=0.92). We conclude that ASCT is not superior to standard CT for treatment of patients with primary refractory HD.
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- 2004
32. Adoptive therapy with donor lymphocyte infusion after allogenic hematopoietic SCT in pediatric patients
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Ewa Gorczyńska, Magdalena Wozniak, Anna Pieczonka, Aleksandra Krasowska-Kwiecień, Mariusz Wysocki, K. Kałwak, K Rewucka, Jerzy Kowalczyk, Jolanta Gozdzik, Agnieszka Zaucha-Prażmo, Robert Dębski, Katarzyna Drabko, Jacek Wachowiak, Alicja Chybicka, and J Krukowska-Jaros
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Male ,Donor lymphocyte infusion ,Disease-Free Survival ,immune system diseases ,hemic and lymphatic diseases ,Living Donors ,Medicine ,Humans ,Child ,Retrospective Studies ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Infant, Newborn ,Infant ,Hematology ,Allografts ,Survival Rate ,Haematopoiesis ,surgical procedures, operative ,Child, Preschool ,Hematologic Neoplasms ,Lymphocyte Transfusion ,Immunology ,Female ,business ,therapeutics ,human activities - Abstract
The aim of this study was to analyse the experience of Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in respect to donor lymphocyte infusion procedure. The study included 51 pediatric patients with malignant (45) and non-malignant (6) diseases treated with DLI in the period 1993-2012. The indications for DLI were as follows: (1) increasing recipient chimerism after non-ablative hematopoietic SCT (18 patients); (2) immunomodulation after a reduced intensity conditioning regimen (2 patients); (3) increase in minimal residual disease detection (3 patients); and (4) relapse (28 patients). DLI was carried out at a median of 6 (0.5-79) months after SCT. DLI was administered as either a single-dose (in 19 cases) or in escalating-dose regimens (in 32 cases). The median total dose of CD3-positive T cells was 28.0 (0.1-730.0) × 10(6)/kg body weight. The time for assessment of DLI efficacy ranged from 0 to 70 (median 3) months. At evaluation, 18 patients experienced CR, 3 achieved PR, 19 showed relapse and 11 rejected the graft. DLI was found to be effective in 39% of cases. Complications of the procedure occurred in 18 patients; of these, 2 died. To sum up DLI shows efficacy in a significant percentage of children. Mortality related to the therapy adverse effects is low. However, this method requires standardization.
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- 2014
33. Visfatin concentrations in children with leukemia before and after stem cell transplantation
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Kamil Fijorek, Aleksandra Krasowska-Kwiecień, Jolanta Gozdzik, Krystyna Sztefko, Przemysław Tomasik, Wojciech Czogała, Szymon Skoczeń, A. Dłużniewska, Oktawiusz Wiecha, Jerzy Starzyk, and Maciej Siedlar
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Carbohydrate metabolism ,chemistry.chemical_compound ,Internal medicine ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,Autografts ,Child ,Nicotinamide Phosphoribosyltransferase ,Molecular Biology ,Leukemia ,Nicotinamide ,business.industry ,Insulin ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,medicine.disease ,Allografts ,Transplantation ,surgical procedures, operative ,Endocrinology ,C-Reactive Protein ,chemistry ,Child, Preschool ,Cytokines ,Female ,Stem cell ,business ,Lipoprotein ,Follow-Up Studies - Abstract
Visfatin (VF) is an adipocytokine that performs many functions, including enhancing cell proliferation and biosynthesis of nicotinamide mononucleotides and dinucleotides. It also seems to be involved in the development of glucose metabolism disturbances. The goal of the study was the determination of VF concentrations in children with leukemia who are treated with stem cell transplantation. VF concentrations were measured in plasma before and after oral glucose tolerance test (OGTT; 60 and 120 minutes) in 22 children with leukemia treated with hematopoietic stem cell transplantation (HSCT) and healthy control subjects (n = 24). The HSCT group was studied twice: before HSCT (22 children) and approximately 6 months after HSCT (12 of 22 children). After fasting, concentrations of glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein, and high-sensitivity C-reactive protein (hsCRP) were determined. Significantly lower (p0.05) median values of VF concentrations at all time points in the OGTT were found in pre- HSCT children compared with control subjects. The median VF concentration was significantly higher after HSCT compared with before HSCT. The decrease in VF in leukemic children in complete remission may be caused by myelosuppression and immunosuppression after prolong chemotherapy and is beneficial because of the decrease in its antiapoptotic activity. VF can serve as an additional biochemical marker for remission in patients with leukemia. Normalization of plasma VF concentration after HSCT might be caused by a process of immune reconstitution and prolonged inflammation (e.g., infections, graft-versus-host disease), injury to organs (e.g., lungs, gut, liver), and endocrinology deficiencies.
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- 2014
34. Chemokine receptors and chemokine production by CD34+ stem cell-derived monocytes in response to cancer cells
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Malgorzata, Stec, Jaroslaw, Baran, Monika, Baj-Krzyworzeka, Kazimierz, Weglarczyk, Jolanta, Gozdzik, Maciej, Siedlar, and Marek, Zembala
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Chemotaxis, Leukocyte ,Cell Line, Tumor ,Neoplasms ,Tumor Microenvironment ,Humans ,Antigens, CD34 ,Receptors, Chemokine ,Cell Communication ,Chemokines ,Fetal Blood ,Flow Cytometry ,Hematopoietic Stem Cells ,Monocytes - Abstract
The chemokine-chemokine receptor (CR) network is involved in the regulation of cellular infiltration of tumours. Cancer cells and infiltrating macrophages produce a whole range of chemokines. This study explored the expression of some CR and chemokine production by cord blood stem cell-derived CD34(+) monocytes and their novel CD14(++)CD16(+) and CD14(+)CD16(-) subsets in response to tumour cells.CR expression was determined by flow cytometry and their functional activity by migration to chemoattractants. Monocytes were cultured with tumour cells and the chemokine content was assessed in culture supernatants.CD14(++)CD16(+) monocytes exhibited increased expression of chemokine (C-C) receptor (CCR) 1, while CD14(+)CD16(-) of CCR2, chemokine (C-X-C) receptor (CXCR) 1, 2 and 4. The increased expression of CCR2 on CD14(+)CD16(-) monocytes was associated with their enhanced migration to monocyte chemoattractant protein-1 (CCL2), MCP-3 (CCL7), MCP-2 (CCL8) and MCP-4 (CCL13), while that of CXCR1 and 2 to interleukin 8 (CXCL8), and CXCR4 to stromal cell-derived factor-1 (CXCL12). Tumour cells induced production of macrophage inflammatory protein-1α (CCL3) MIP-1β and regulated on activation normal T-cells expressed and secreted (CCL5) but not CCL2 or CXCL8, monokine induced by gamma interferon (CXCL9), interferon gamma-induced protein 10 (CXCL10).The studied monocyte subsets, in comparison to those from blood, exhibit different expression of CRs and response to the stimuli that occur from tumour cells.
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- 2012
35. Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation compared to conventional anticancer therapy: a multicentre nationwide study
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Elżbieta Drożyńska, Jolanta Gozdzik, Tomasz Ociepa, Alicja Chybicka, Danuta Perek, Walentyna Balwierz, Grażyna Sobol-Milejska, Lidia Gil, K. Kałwak, Tomasz Urasiński, Weronika Stolpa, Jowita Fraczkiewicz, Grażyna Karolczyk, Krzysztof Czyżewski, Liliana Chełmecka-Wiktorczyk, Wanda Badowska, Jacek Wachowiak, Marcin Płonowski, Agnieszka Zaucha-Prażmo, Olga Gryniewicz-Kwiatkowska, Filip Pierlejewski, Jan Styczyński, Mariola Woszczyk, Renata Tomaszewska, Lukasz Hutnik, Maryna Krawczuk-Rybak, Zuzanna Gamrot, Olga Zajac-Spychala, Zofia Małas, Agnieszka Urbanek-Dadela, Bożenna Dembowska-Bagińska, A. Kolodziejczyk-Gietka, Jerzy Kowalczyk, Wojciech Młynarski, Małgorzata Salamonowicz, Tomasz Szczepański, Ninela Irga-Jaworska, M. Matysiak, Mariusz Wysocki, and Karolina Siewiera
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Microbiology (medical) ,medicine.medical_specialty ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,medicine.disease_cause ,Transplantation, Autologous ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Cumulative incidence ,Child ,Survival rate ,business.industry ,Incidence ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Varicella zoster virus ,Infant ,Bacterial Infections ,General Medicine ,BK virus ,Survival Rate ,Transplantation ,Infectious Diseases ,Mycoses ,Virus Diseases ,Child, Preschool ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Immunology ,Poland ,business ,030215 immunology - Abstract
This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.
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- 2016
36. Consolidation of first-line therapy with busulphan and melphalan, and autologous stem cell rescue in children with Ewing’s sarcoma
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Jerzy Kowalczyk, Marek Ussowicz, Katarzyna Bilska, Agnieszka Zaucha-Prażmo, Ewa Gorczyńska, Jolanta Gozdzik, Marta Choma, Anna Raciborska, Beata Wójcik, Szymon Skoczeń, Katarzyna Drabko, Mariusz Wysocki, Jan Styczyński, Alicja Chybicka, and W Wozniak
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Adult ,Male ,Melphalan ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Bone Neoplasms ,Sarcoma, Ewing ,autologous transplantation ,Young Adult ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Risk factor ,Child ,Busulfan ,Randomized Controlled Trials as Topic ,Retrospective Studies ,Transplantation ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Infant, Newborn ,Infant ,Ewing's sarcoma ,Retrospective cohort study ,Consolidation Chemotherapy ,Hematology ,medicine.disease ,Combined Modality Therapy ,Surgery ,Radiation therapy ,Child, Preschool ,high-dose therapy ,Female ,Sarcoma ,business ,Ewing0s sarcoma ,medicine.drug - Abstract
According to the published report on current practice of hematopoietic SCT in Europe, high-dose therapy (HDT) with autologous stem cell support is a standard of care in paediatric patients with high risk (HR) or relapsed Ewing's sarcoma (ES). Randomized trials, however, have not confirmed the value of this procedure yet. In this retrospective analysis we intended to evaluate the role of HDT as a consolidation therapy in first remission of ES. A total of 102 patients were included in the analysis and divided according to the following risk factors: metastatic disease at presentation, feasibility of surgery and histological response after induction. Forty-one patients were classified as standard risk (SR) patients, while the remaining 61 children, with at least one risk factor, were classified as HR patients. HR group patients were non-randomized and qualified according to the decision of the local clinician to give a conventional consolidation (CC) or to perform high-dose chemotherapy and radiotherapy in selected patients. Twenty-six children were given CC while 35 patients were treated with HDT. The HDT consisted of oral BU 4 mg/kg p.o. in divided doses daily for 4 days (total dose 16 mg/kg) followed by melphalan 140 mg/m(2) i.v. on day -2. Probability of relapse-free survival (RFS) in median observation time was significantly worse in HR patients who were given CC therapy as compared with children with HR features receiving high-dose chemotherapy (0.27 vs 0.66 (P = 0.008); OS 0.31 vs 0.71 (P = 0.007), respectively). Patients from the SR group had a probability of RFS of 0.72 and OS of 0.75, and the difference between SR and HR patients after HDT was NS (P = 0.37). Our observation confirms that the consolidation of the first-line treatment with BU and melphalan improves the outcome in ES patients with HR features.
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- 2012
37. Risk of complications during hematopoietic stem cell collection in pediatric sibling donors: A prospective European Group for Blood and Marrow Transplantation Pediatric Diseases Working Party study
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Miguel Angel Diaz, Franca Fagioli, Giorgio Dini, Jolanta Gozdzik, Adriana Balduzzi, Jacek Wachowiak, Chiara Messina, Jean-Hugues Dalle, Jelena Rascon, Matthias Eyrich, Myriam Labopin, Karoline Ehlert, Lidia Gil, Christina Peters, Christiane Vermylen, Rose-Marie Hamladji, Sarah Marktel, Maurizio Miano, M. Akif Yesilipek, Isabel Badell, Daphna Hutt, Martina Matulova, Jan Styczyński, Peter Dreger, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, Styczynski, J, Balduzzi, A, Gil, L, Labopin, M, Hamladji, R, Marktel, S, Yesilipek M., A, Fagioli, F, Ehlert, K, Matulova, M, Dalle, J, Wachowiak, J, Miano, M, Messina, C, Diaz Miguel, A, Vermylen, C, Eyrich, M, Badell, I, Dreger, P, Gozdzik, J, Hutt, D, Rascon, J, Dini, G, and Peters, C
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Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Immunology ,Blood Specimen Collection ,Bone Marrow Transplantation ,Child ,Child, Preschool ,Female ,Humans ,Infant ,Infant, Newborn ,Peripheral Blood Stem Cell Transplantation ,Siblings ,Hematopoietic Stem Cell Transplantation ,Tissue Donors ,Hematology ,Biochemistry ,Cell Biology ,Hematopoietic stem cell transplantation ,medicine ,Adverse effect ,Preschool ,hematopoietic stem cell transplantation, sibling, complications, stem cell donor, pediatric ,business.industry ,Hematopoietic stem cell ,medicine.disease ,Newborn ,medicine.anatomical_structure ,Apheresis ,Pneumothorax ,Donation ,Hydrothorax ,business ,Central venous catheter - Abstract
We investigated prospectively factors influencing the safety of hematopoietic stem cell (HSC) collection in 453 pediatric donors. The children in the study donated either BM or peripheral blood stem cells (PBSCs) according to center policy. A large variability in approach to donor issues was observed between the participating centers. Significant differences were observed between BM and PBSC donors regarding pain, blood allotransfusion, duration of hospital stay, and iron supplementation; however, differences between the groups undergoing BM vs PBSC donation preclude direct risk comparisons between the 2 procedures. The most common adverse event was pain, reported mainly by older children after BM harvest, but also observed after central venous catheter (CVC) placement for PBSC collection. With regard to severe adverse events, one patient (0.7%) developed a pneumothorax with hydrothorax after CVC placement for PBSC collection. The risk of allotransfusion after BM harvest was associated with a donor age of < 4 years and a BM harvest volume of > 20 mL/kg. Children < 4 years were at higher risk than older children for allotransfusion after BM harvest and there was a higher risk of complications from CVC placement before apheresis. We conclude that PBSC and BM collection are safe procedures in children. (Blood. 2012;119(12):2935-2942) We investigated prospectively factors influencing the safety of hematopoietic stem cell (HSC) collection in 453 pediatric donors. The children in the study donated either BM or peripheral blood stem cells (PBSCs) according to center policy. A large variability in approach to donor issues was observed between the participating centers. Significant differences were observed between BM and PBSC donors regarding pain, blood allotransfusion, duration of hospital stay, and iron supplementation; however, differences between the groups undergoing BM vs PBSC donation preclude direct risk comparisons between the 2 procedures. The most common adverse event was pain, reported mainly by older children after BM harvest, but also observed after central venous catheter (CVC) placement for PBSC collection. With regard to severe adverse events, one patient (0.7%) developed a pneumothorax with hydrothorax after CVC placement for PBSC collection. The risk of allotransfusion after BM harvest was associated with a donor age of < 4 years and a BM harvest volume of > 20 mL/kg. Children < 4 years were at higher risk than older children for allotransfusion after BM harvest and there was a higher risk of complications from CVC placement before apheresis.We conclude that PBSC and BM collection are safe procedures in children. © 2012 by The American Society of Hematology.
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- 2012
38. Homozygosity for the rs9939609T allele of the FTO gene may have protective effect on becoming overweight in survivors of childhood acute lymphoblastic leukaemia
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Jacek J Pietrzyk, Jolanta Gozdzik, Marcin Surmiak, Walentyna Balwierz, Danuta Galicka-Latała, Skoczen Szymon, Miroslaw Bik-Multanowski, and Wojciech Strojny
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Male ,medicine.medical_specialty ,Adolescent ,Population ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Overweight ,Biology ,FTO gene ,Polymorphism, Single Nucleotide ,Young Adult ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,medicine ,Odds Ratio ,overweight ,Asparaginase ,Humans ,Obesity ,Survivors ,education ,Child ,Thioguanine ,Cyclophosphamide ,Genetic Association Studies ,education.field_of_study ,Radiotherapy ,Daunorubicin ,Homozygote ,Cytarabine ,nutritional and metabolic diseases ,Proteins ,Odds ratio ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Methotrexate ,Vincristine ,Child, Preschool ,Attributable risk ,leukaemia ,Prednisone ,Female ,Population Risk ,medicine.symptom ,FTO - Abstract
Approximately 20% of adolescents and children in Europe are overweight, and 30% of those who are overweight actually fulfill the criteria of obesity (Branca et al. 2007). The prevalence of obesity in survivors of acute lymphoblastic leukaemia (ALL) is 16 to 57% (Gregory and Reilly 2004). Among others, cranial radiotherapy (CRT) and genetic factors have been implicated as risk factors of overweight/obesity (Ross et al. 2004; Chow et al. 2007). The fat mass and obesity associated gene (FTO) has been recently found to contribute to the risk of obesity. Polymorphism of rs9939609 T>A was associated with an increased BMI in children aged ≥7 years. Individuals homozygous for A allele at rs9939609 constituted 16% of the population and population risk was 20.4% for obesity and 12.7% for overweight (Frayling et al. 2007). The high-risk FTO haplotype yielded a proportion of attributable risk of 22% for uncomplicated obesity in adults and children of European ancestry (Dina et al. 2007). Therefore, the influence of rs9939609 T>A polymorphism of FTO gene on overweight in leukaemia survivors was studied. A total of 191 patients were genotyped for the above genetic variant. Significant negative association between the rs9939609T allele and prevalence of overweight status was found in a subset of patients treated with CRT. Patients who receive CRT and are carriers of this variant may be protected from becoming overweight.
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- 2011
39. Plasma levels of leptin and soluble leptin receptor and polymorphisms of leptin gene -18G > A and leptin receptor genes K109R and Q223R, in survivors of childhood acute lymphoblastic leukemia
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Krystyna Sztefko, Szymon Skoczeń, Marcin Surmiak, Jacek J Pietrzyk, Jolanta Gozdzik, Danuta Galicka-Latała, Wojciech Strojny, Przemysław Tomasik, Walentyna Balwierz, and Miroslaw Bik-Multanowski
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Leptin ,Male ,growth hormone deficiency ,denature high performance liquid chromatography ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Genotype ,body mass index percentile ,Context (language use) ,acute lymphoblastic leukemia ,Overweight ,lcsh:RC254-282 ,Polymorphism, Single Nucleotide ,Growth hormone deficiency ,Internal medicine ,medicine ,Humans ,Survivors ,Child ,Childhood Acute Lymphoblastic Leukemia ,Leptin receptor ,Anthropometry ,business.industry ,Research ,Infant ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Obesity ,Regimen ,Endocrinology ,Oncology ,Child, Preschool ,overweight status ,Receptors, Leptin ,Female ,medicine.symptom ,business - Abstract
Background Approximately 20% of children and adolescents in Europe are overweight. Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk of overweight and obesity. The purpose of this study was to assess leptin and leptin soluble receptor levels, as well as polymorphisms of selected genes in survivors of pediatric ALL, and the influence of chemo- and radiotherapy on development of overweight in the context of leptin regulation. Methods Eighty two patients (55% males), of median age 13.2 years (m: 4.8 years; M: 26.2 years) were included in the study. The ALL therapy was conducted according to modified Berlin-Frankfurt-Munster (BFM; n = 69) regimen or New York (n = 13) regimen. In 38% of patients cranial radiotherapy (CRT) was used in median dose of 18.2Gy (m: 14Gy; M: 24Gy). Median age at diagnosis was 4.5 (m: 1 year; M: 16.9 years) and median time from completion of ALL treatment was 3.2 years (m: 0.5 year; M: 4.3 years). Patients with BMI ≥85 percentile were classified as overweight. Correlation of plasma levels of leptin and leptin soluble receptor, and polymorphisms of leptin gene -18G > A, leptin receptor genes K109R and Q223R, and the overweight status were analyzed in relation to gender, intensity of chemotherapy (high intensity vs. standard intensity regimens) and to the use of CRT. Results Significant differences of leptin levels in patients treated with and without CRT, both in the entire study group (22.2+/- 3.13 ng/ml vs. 14.9+/-1.6 ng/ml; p < 0.03) and in female patients (29.9+/-4.86 ng/ml vs. 16.9+/-2.44 ng/ml; p = 0.014), were found. Significant increase of leptin levels was also found in overweight patients compared to the non-overweight patients in the entire study group (29.2+/-2.86 ng/ml vs. 12.6+/-1.51 ng/ml; p < 0.0001), female patients (35.4+/-6.48 ng/ml vs. 18.4+/-2.5 ng/ml; p = 0.005), and male patients (25.7+/-2.37 ng/ml vs. 6.9+/-0.95 ng/ml; p < 0.0001). Negative correlation was observed for plasma levels of soluble leptin receptor and overweight status, with significant differences in overweight and non-overweight patients, both in the entire study group (18.2+/-0.75 ng/ml vs. 20.98+/-0.67 ng/ml; p = 0.017) and in male patients (18.2+/-1.03 ng/ml vs. 21.8+/- 1.11 ng/ml; p = 0.038). Significant (p < 0.05) negative correlation was found between leptin and leptin receptor levels in the entire group (correlation coefficient: 0.393) and in both gender subgroups (correlation coefficient in female patients: -0.427; in male patients: -0.396). Conclusions The prevalence of overweight in our cohort was higher than in general European population (31% vs 20%) and increased regardless of the use of CRT. Leptin and leptin receptor levels may be used as useful markers of high risk of becoming overweight in ALL survivors, particularly in females treated with CRT. Polymorphisms of leptin gene -18G > A and leptin receptor genes K109R and Q223R were not associated with overweight status in ALL survivors.
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- 2011
40. [Can brain-machine interface improve quality of life of patients with chronic motor dysfunction?]
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Szymon, Skoczeń, Jolanta, Gozdzik, Aleksandra, Krasowska-Kwiecień, Oktawiusz, Wiecha, Wojciech, Czogała, Anna, Wedrychowicz, and Dorota, Zygadło
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User-Computer Interface ,Wheelchairs ,Quality of Life ,Stroke Rehabilitation ,Humans ,Brain Damage, Chronic ,Equipment Design ,Neuromuscular Diseases ,Man-Machine Systems - Abstract
In departments of neurology, neurosurgery and hospice care there is a group of patients with compete motor function impairment having normal central nervous system function. Victims of spinal cord injury, cerebral palsy, cerebral stroke, loss of extremities, neuromuscular diseases, between others belong to them. Since two decades an intensive studies of use of brain waves to steer peripheral equipments has been performed. Brain Computer Interface and Brain-Machine Interface will allow in the near future for even partial restore of skills in permanently disabled patients. Recently new sets composed of games steered by brain waves have been introduced to the market. Exercises with such equipment will help to control an ability to concentrate and precise steer of the peripheral electronic equipments. The next phase will be use of the new skills to steer the wheelchairs and other computer programs with the brain signals to control own healthy organs or artificial machines.
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- 2010
41. [Sinusoidal obstruction disease (SOS), previous hepatic venoocclusive disease (VOD)--still serious complication after hematopoietic stem cell transplantation]
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Jolanta, Gozdzik, Aleksandra, Krasowska-Kwiecień, and Anna, Wedrychowicz
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Treatment Outcome ,Recurrence ,Hematopoietic Stem Cell Transplantation ,Hepatic Veno-Occlusive Disease ,Humans - Abstract
Hepatic venocclusive disease (VOD) lastly named sinusoidal obstruction syndrome (SOS) is a serious toxicity associated with high dose therapy used to prepare patients for stem cell transplantation. A sizable proportion of patients who develop VOD/SOS die. It is clear that injury to endothelial cells and hepatocytes in zone 3 of the liver acinus is the initial event in the pathogenesis of VOD/SOS. Although clinical presentation and diagnostic criteria are well known, the cause of VOD/SOS, its prevention and treatment remain still unclear. Currently treatment of VOD/SOS has largely consisted of supportive measures designed to maintain intravascular volume and decrease interstitial edema. Other treatments used with various measures of success have included substitution of antitrombine and glutamine or aggressive fibrinolitic and antithrombotic therapy. Despite these treatments, the outcome remains fairly dismal.
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- 2008
42. [Why should we revaccinate children after stem cell transplantations?]
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Ewa, Kacińska, Jolanta, Gozdzik, and Hanna, Czajka
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Infection Control ,Vaccines ,Transplantation Conditioning ,Antibody Formation ,Vaccination ,Humans ,Poland ,Child ,Communicable Diseases ,Immunization Schedule ,Bone Marrow Transplantation ,Stem Cell Transplantation - Abstract
Stem cell transplantation is a procedure often used in treatment of proliferative and non-prolifarative diseases. Recipient's immunological system has been damaged during pretransplant and conditioning therapy: deprived from B- and T-cell mediated immunological response and memory cells. One of the prophylactic procedures against post-transplant infections in recipients is efficient and safe revaccination. In Poland so far there is no uniform revaccination schedule for stem cell transplantation recipients.
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- 2008
43. Atrial Natriuretic Factor in Untreated Hyperthyroidism
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Jolanta Gozdzik, Urszula Majewska, Krystyna Widecka, Tomasz Dutkiewicz, and Stanislaw Czekalski
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Adult ,Male ,Thyroid Hormones ,endocrine system ,030213 general clinical medicine ,medicine.medical_specialty ,endocrine system diseases ,Clinical Biochemistry ,Blood Pressure ,030209 endocrinology & metabolism ,Peptide hormone ,Hyperthyroidism ,03 medical and health sciences ,0302 clinical medicine ,Atrial natriuretic peptide ,Heart Rate ,Internal medicine ,Blood plasma ,Heart rate ,otorhinolaryngologic diseases ,medicine ,Humans ,Chemistry ,Sodium ,Radioimmunoassay ,General Medicine ,Middle Aged ,Blood pressure ,Endocrinology ,Thyroid hormones ,Plasma concentration ,Potassium ,cardiovascular system ,Female ,Atrial Natriuretic Factor ,hormones, hormone substitutes, and hormone antagonists - Abstract
Increased plasma concentration of atrial natriuretic factor (ANF) in untreated hyperthyroid patients is reported. A significant positive correlation between the concentration of ANF and serum thyroid hormones (T4 and T3) has been found when hyperthyroid patients and healthy controls were pooled together. The mechanism by which thyroid hormones raise plasma ANF concentration and its relevance to the symptomatology of hyperthyroidism is discussed.
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- 1990
44. HSP90 antagonist, geldanamycin, inhibits proliferation, induces apoptosis and blocks migration of rhabdomyosarcoma cells in vitro and seeding into bone marrow in vivo
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Marcin Majka, Oktawiusz Wiecha, Jolanta Gozdzik, Ewa Lesko, Bartosz Jenner, and Jacek Kijowski
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musculoskeletal diseases ,Cancer Research ,medicine.medical_specialty ,genetic structures ,Lactams, Macrocyclic ,Apoptosis ,Bone Marrow Cells ,Mice, SCID ,Biology ,Hsp90 inhibitor ,chemistry.chemical_compound ,Mice ,Neoplasm Seeding ,Internal medicine ,Cell Line, Tumor ,medicine ,Benzoquinones ,Animals ,Humans ,Pharmacology (medical) ,Rhabdomyosarcoma, Embryonal ,HSP90 Heat-Shock Proteins ,Rhabdomyosarcoma ,Rhabdomyosarcoma, Alveolar ,Cell Proliferation ,Pharmacology ,Antibiotics, Antineoplastic ,Cell growth ,musculoskeletal, neural, and ocular physiology ,Chemotaxis ,Apoptosis Inducing Factor ,Geldanamycin ,Cell cycle ,medicine.disease ,eye diseases ,Endocrinology ,medicine.anatomical_structure ,Oncology ,chemistry ,Cell culture ,Cancer research ,Hepatocyte growth factor ,Bone marrow ,human activities ,medicine.drug - Abstract
In this study, geldanamycin (GA) was found to have an antiproliferative effect on both embryonal and alveolar rhabdomyosarcoma (RMS) cell lines. The maximum level of inhibition reached 80% for both embryonal and alveolar RMS. After GA treatment, cells also became apoptotic as judged by Annexin V-positive staining, activation of caspase-3 pathway and poly(ADP ribose) polymerase cleavage. GA was responsible for the arrest of RMS cells in both G 1 and G 2 /M phases of the cell cycle. G 1 blockade, however, was transient and was seen only in the first 24 h of GA treatment RMS often gives distant metastases to various organs including bone marrow. RMS cells express high levels of MET receptor and respond to hepatocyte growth factor with increased motility. In our study, we found that GA decreased the level of MET expression and inhibited the chemotaxis of RMS cells toward the hepatocyte growth factor gradient. GA also blocked the homing of RMS cells into bone marrow of severe combined immune deficient mice. In all our experiments embryonal RMS cell lines were significantly more sensitive, and lower concentrations of GA were sufficient to block embryonal RMS cell proliferation, induce apoptosis and inhibit motility. Our data show that the HSP90 inhibitor GA has the potential to become a new drug in RMS treatment. It blocks RMS proliferation, decreases cell survival and inhibits motility of RMS cells.
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- 2007
45. The migration of bone marrow-derived non-hematopoietic tissue-committed stem cells is regulated in an SDF-1-, HGF-, and LIF-dependent manner
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Janina Ratajczak, Marcin Majka, Mariusz Z. Ratajczak, Jolanta Gozdzik, Ryan Reca, Magda Kucia, Bogdan Machalinski, Jarek Baran, and Wojtek Wojakowski
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Receptors, CXCR4 ,Leukemia Inhibitory Factor Receptor alpha Subunit ,Receptors, OSM-LIF ,Immunology ,Bone Marrow Cells ,CXCR4-SDF-1 ,Biology ,CXCR4 ,Leukemia Inhibitory Factor ,Models, Biological ,stem cell plasticity ,Mice ,Cell Movement ,medicine ,Immunology and Allergy ,Animals ,Humans ,Tissue Distribution ,Receptors, Cytokine ,Bone Marrow Transplantation ,Mice, Inbred BALB C ,Hepatocyte Growth Factor ,Interleukin-6 ,Stem Cells ,Hematopoietic Tissue ,Age Factors ,Hematopoietic stem cell ,General Medicine ,Proto-Oncogene Proteins c-met ,Molecular biology ,Chemokine CXCL12 ,stem cell mobilization ,Cell biology ,LIF-R-LIF ,c-MET-HGF ,Haematopoiesis ,medicine.anatomical_structure ,Gene Expression Regulation ,regeneration ,Leukocyte Common Antigens ,Hepatocyte growth factor ,Female ,Bone marrow ,Stem cell ,Leukemia inhibitory factor ,Chemokines, CXC ,medicine.drug - Abstract
Introduction: Recently we identified in bone marrow (BM) by employing chemotactic isolation to SDF-1 gradient combined with real time RT-PCR analysis a mobile population of CXCR4+ BM mononuclear cells that express mRNA for various markers of early tissue-committed stem cells (TCSCs). In this study we evaluated whether TCSCs respond to other motomorphogens, such as hepatocyte growth factor (HGF) and leukemia inhibitory factor (LIF). Materials and Methods: We again employed chemotactic isolation combined with real-time RT-PCR analysis to assess whether murine and human BM contain TCSCs that respond to HGF and LIF gradients. We also evaluated expressions of HGF and LIF in damaged organs. Results: We noted that the number of TCSCs is highest in BM from young (1- to 2-month-old) mice and decreases in 1-year–old animals. Murine and human TCSCs 1) respond to HGF and LIF gradients in addition to an SDF-1 gradient, 2) reside in populations of BM-derived non-hematopoietic CD45−cells, and 3) are released (mobilized) from BM into the peripheral blood (PB) during tissue injury (e.g. after partial body irradiation). Conclusions: These findings further support our theory of the BM as a “hideout” for TCSCs and we suggest that their presence in BM tissue should be considered before experimental evidence is interpreted simply as transdifferentiation/plasticity of hematopoietic stem cells. Since we demonstrated that not only SDF-1, but also HGF and LIF are upregulated in damaged tissues, we postulate that CXCR4+ c-Met+ LIF-R+ TCSC could be mobilized from the BM into the PB, from which they are subsequently chemoattracted to damaged organs, where they play a role in tissue repair/regeneration.
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- 2006
46. Factors Modifying Outcome After MIBG Therapy in Children With Neuroblastoma—A National Retrospective Study
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Marek Ussowicz, Aleksandra Wieczorek, Agnieszka Dłużniewska, Anna Pieczonka, Robert Dębski, Katarzyna Drabko, Jolanta Goździk, Walentyna Balwierz, Daria Handkiewicz-Junak, and Jacek Wachowiak
- Subjects
MIBG ,high-dose chemotherapy ,pediatric ,hematopoietic stem cell transplant ,treosulfan-based conditioning ,busulfan and melphalan ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundNeuroblastoma is the most common pediatric extracranial tumor with varied prognoses, but the survival of treated refractory or relapsing patients remains poor.ObjectiveThis analysis presents the outcomes of children with neuroblastoma undergoing MIBG therapy in Poland in 2006-2019.Study DesignA retrospective cohort of 55 patients with refractory or relapsed neuroblastoma treated with I-131 MIBG in Poland in 2006-2019 was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of second cancers and CI of hypothyroidism. Survival curves were estimated using the Kaplan-Meier method and compared between the cohorts by the log-rank test. Cox modeling was adopted to estimate hazard ratios for OS and EFS, considering factors with P < 0.2.ResultsFifty-five patients with a median age of 78.4 months (range 18-193) with neuroblastoma underwent one or more (4 patients) courses of MIBG I-131 therapy. Fifteen patients were not administered chemotherapy, 3 children received standard-dose chemotherapy, and 37 patients were administered high-dose chemotherapy (HDCT) (busulfan-melphalan in 24 and treosulfan-based in 12 patients). Forty-six patients underwent stem cell transplantation, with autologous (35 patients), haploidentical (6), allogeneic (4), and syngeneic grafts (1). The median time from first MIBG therapy to SCT was 22 days. Children with relapsing tumors had inferior OS compared to those with primary resistant disease (21.2% vs 58.7%, p=0.0045). Survival was better in patients without MYCN gene amplification. MIBG therapy was never curative, except in patients further treated with HDCT with stem cell rescue irrespective of the donor type. 31 patients were referred for immune therapy after MIBG therapy, and the 5-year OS in this group was superior to the untreated children (55.2% vs 32.7%, p=0.003), but the difference in the 5-year EFS was not significant (25.6% vs 32.9%, p=ns). In 3 patients, a second malignancy was diagnosed. In 19.6% of treated children, hypothyroidism was diagnosed within 5 years after MIBG therapy.ConclusionMIBG therapy can be incorporated into the therapeutic strategy of relapsed or resistant neuroblastoma patients as preconditioning with HDCT rather than stand-alone therapy. Follow-up is required due to the incidence of thyroid failure and risk of second cancers.
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- 2021
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47. LIF-LIF-R and SDF-1-CXCR4 Axes Regulate Overlapping and Complementary Steps of Metastasis of Rhabdomyosarcoma - Implication for Developing Better Antimetastatic Therapies.
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Miekus, Kasia, primary, Wysoczynski, Marcin, primary, Reca, Ryan, primary, Jolanta, Gozdzik, primary, Salvatore, Bertolone J., primary, Janowska-Wieczorek, Anna, primary, and Ratajczak, Mariusz Z., primary
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- 2005
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48. New GvHD Mouse Model for Assessing Both Acute and Chronic Phase of the Disease
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Witold Miezynski, Marcin Majka, Anna Wędrychowicz, Jolanta Gozdzik, Leszek Wojakiewicz, Oktawiusz Wiecha, and Anna Zebzda
- Subjects
education.field_of_study ,Pathology ,medicine.medical_specialty ,business.industry ,Immunology ,Population ,Spleen ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Transplantation ,Haematopoiesis ,medicine.anatomical_structure ,Graft-versus-host disease ,Syngeneic Graft ,Weight loss ,medicine ,medicine.symptom ,education ,business ,CD8 - Abstract
Graft versus host disease (GvHD) is still a very serious problem in hematopoietic stem cells transplantation which makes searching for new possibilities of its prevention and treatment necessary. Animal models are very useful tools for such research. We present a mouse model of GvHD allowing observation of both acute and chronic phase of the disease. C57Bl/6 mice (H-2b) were transplanted, one day after ablative TBI with 5×106 BM cells and 4×106 or 10×106 splenocytes isolated from allogeneic C3H. He (H-2k) or from syngeneic animals. Sex mismatched transplants were performed and chimerism of transplanted animals was confirmed by detection of sry gene with PCR. As a control group for blood examination after transplantation C3H syngeneic transplantations were performed. After transplantation, mice were weighted and physically examined by looking for changes in skin, posture, physical activity and peripheral blood parameters. Histopathological examination was performed on day +8, +16, +31 in some of the animals. Autopsy was also performed on mice which died during the experiment or which body weight decreased below 65% of the initial weight. We observed a characteristic pattern of physical symptoms of GvHD including weight loss, skin desquamation, hunching and loss of activity, diarrhea. Weight loss to 88.2% of the initial body weight on day +7 was followed by a return to the initial weight (101.1%) on day +14 and then another decrease either strong and leading to the death of the animal or moderate and leading to a long time plateau (the average body weight on days +31, +59 and +101 was 94.4%, 91.7% and 93.6%). On day +7 desquamation of the skin of paws was very well visible and since day +10 gradually intensifying desquamative changes of the skin of whole body were observed - the mean level of changes in the population was highest on days +21 to + 24. Interestingly areas of the skin which were nude before TBI and transplantation were affected earlier (changes were visible on day +7) and more severly than other regions of the skin suggesting that local more intensive damage caused by irradiation can locally aggravate the course of GvHD. The physical symptoms were accompanied with histopathological changes of liver, skin, spleen and gut. Neither physical nor histopathological symptoms of the disease were observed in mice transplanted with syngeneic cells. In fluorocytometric analysis of peripherial blood performed on days +17, +31 and +45 severe lymphopenia was observed. The average number of CD3+CD4+, CD3+CD8+ and B220+ cells was strongly decreased in animals transplanted with allogeneic cells as compared to syngeneic graft recipients. At the same time expression of CD69 activation antigen on CD4+ and CD8+ cells was strongly increased in allograft recipients as compared to syngeneic controls. The course of the disease, including weight loss and skin changes, was generally less severe in the population of mice transplanted with BM + 4×106 splenocytes as compared to BM + 10×106 of splenocytes recipients. The 25th, 50th and 75th percentiles of survival function for both populations were162, 301, 405 and 45, 88, 277 days, respectively.
- Published
- 2006
49. Comparison of Myeloma Cells Killing Efficiency by Geldanamycin and Its Analogs
- Author
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Aleksander B. Skotnicki, Wojciech Czogała, Artur Jurczyszyn, Marcin Majka, Jolanta Gozdzik, Ewa Lesko, and Anna Zebzda
- Subjects
biology ,business.industry ,Immunology ,Cell Biology ,Hematology ,Geldanamycin ,Cell cycle ,medicine.disease ,Biochemistry ,Hsp90 ,chemistry.chemical_compound ,chemistry ,Cell culture ,Apoptosis ,Heat shock protein ,Cancer research ,biology.protein ,medicine ,Growth inhibition ,business ,Multiple myeloma - Abstract
Multiple Myeloma (MM) is the second most commonly diagnosed hematologic malignancy and still an incurable disease with dismal prognosis and average survival of 3 – 4 years. None of conventional therapies gives total cure or long survival, so it is urgently necessary to find new treatment strategies. Heat shock protein 90 (HSP90) is a potentially good therapeutic target, because it interacts with diverse and wide panel of client proteins that are important for proliferation and survival of tumor cells. Geldanamycin (GA) and its analog 17-allylaminogeldamycin (17AAG) are HSP90 inhibitors and were shown to block various tumor cells growth including MM cells. 17AAG has been already tested in clinical trials and showed some antitumor properties. There are, however, other inhibitors belonging to geldanamycin family such as: 17DMAG, 17DMAP and 17AEP which have not been tested against multiple myeloma cell lines and primary samples. In this study we looked at the influence of GA and its analogs on proliferation and apoptosis of MM cells. We found that GA at 100 nM concentration inhibited growth of MM cells by 80%, 17AEP by 75%, 17DMAG and 17DMAP by 70% and 17AAG by 30%. Primary MM cells were more resistant and at 100 nM concentration we observed 30% inhibition with GA and 17DMAG. At the same time 17AAG did not effectively inhibit proliferation of primary MM cells. We also analyzed influence of 100 nM concentration of GA and analogs on the apoptosis of MM primary cells and cell lines after 6 h and 24 h of incubation. Percentage of Anexin V and propidium iodine double positive geldanamycines treated primary MM cells was similar to the control after 6 h but change after 24 h. In comparison to control, number of apoptotic cells increased by: 175% for 17DMAG, 140% for GA, 80% for 17DMAP and 17AEP, no changes in number of apoptotic cells were observed for 17AAG. Similar observation was made for MM cell lines and increase in number of Anexin V positive cells was noticed. Again, percentage of Anexin V positive cells did not increase after treatment with 17AAG and remained at the control level. We also observed, similarly to others, substantial block in G1 and G2/M phase of cell cycle in cells treated with GA and its analogs. In conclusion, besides to 17AAG other HSP90 inhibitors could be considered as potential therapeutics for treatment of MM. Particularly, based on our data, we suggest that 17DMAG and 17AEP are new HSP90 inhibitors that should be tested in a clinic because they exert strong MM cells growth inhibition.
- Published
- 2006
50. Unexpected Evidence That Dimethylsulphoxide (DMSO) Upregulates Expression of CXCR4 on Hematopoietic Stem/Progenitor Cells (HSPC), Increases Their Responsiveness to an SDF-1 Gradient and Enhances Homing to Bone Marrow
- Author
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Jolanta Gozdzik, Danuta Jarocha, Marcin Majka, Jacek Kijowski, Duygu Sag, Ewa K. Zuba-Surma, Marcin Wysoczynski, and Mariusz Z. Ratajczak
- Subjects
Immunology ,CD34 ,Cell Biology ,Hematology ,Biology ,CD38 ,Biochemistry ,Molecular biology ,Transplantation ,Haematopoiesis ,medicine.anatomical_structure ,Cord blood ,medicine ,Bone marrow ,Progenitor cell ,Homing (hematopoietic) - Abstract
Cryopreservation of bone marrow (BM), mobilized peripheral blood (mPB) and cord blood (CB) cells is a routine procedure to store hematopoietic stem/progenitor cells (HSPC) for transplantation. Dimethylsulphoxide (DMSO), the most commonly used cryoprotectant, is toxic to cells at higher concentrations (>10%); moreover, the freezing-thawing procedure itself is inevitably connected with the loss of HSPC. However, by chance we observed that short exposure of HSPC to DMSO enhances the responsiveness of these cells to an SDF-1 gradient and since SDF-1 is a major chemoattractant that navigates homing of HSPC to BM we became interested in elucidating this phenomenon. We found that short incubation (5–10 min) of human CB mononuclear cells (MNC) with DMSO at concentrations employed for cryopreservation (5–10%) significantly upregulates the expression of both CXCR4 (x 2–3) and CD34 (x 1.5) on CB MNC (as measured by FACS). Furthermore, DMSO significantly increased the chemotactic responsiveness (x 2–4) of CB MNC, BM MNC and selected CXCR4+ human hematopoietic cell lines (Jurkat, THP-1 cells) when the cells were exposed to 5–10% DMSO before chemotaxis assay. These responses to an SDF-1 gradient correlated with enhanced chemotaxis also of human CD34+, CD34+ CD38+, CD34+ CD38−, and CD34+ CXCR4+ clonogeneic progenitor cells, suggesting that DMSO directly enhances the responsiveness of human early progenitors (p
- Published
- 2005
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