423 results on '"Jindra, Pavel"'
Search Results
152. Successful Peripheral Blood Stem Cells Collection in Imatinib Pretreated and Nilotinib-Treated ChronicMyeloid Leukemia Patient.
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Vokurka, Samuel, Koza, Vladimir, Lysak, Daniel, Karas, Michal, Dvorak, Pavel, Jindra, Pavel, Hrabetova, Marcela, and Vozobulova, Vera
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CANCER treatment ,CHRONIC myeloid leukemia ,DRUG therapy ,IMATINIB ,ANTINEOPLASTIC agents ,PROTEIN-tyrosine kinase inhibitors ,GRANULOCYTE-colony stimulating factor ,PATIENTS - Abstract
We report a case of a successful mobilization and harvest of the peripheral blood stem cells (PBSCs) in imatinib-pretreated and nilotinib treated 52-year-old woman diagnosed with Philadelphia chromosome-positive and BCR-ABL (b2a2) positive chronic phase CML in 2/2002. She failed interferon-alfa and imatinib treatment. She achieved her first complete molecular remission after 16 months of nilotinib treatment and later on was mobilized with filgrastim at a dose of 10 ug/kg/day applied subcutaneously once daily. The total number of 2.98 × 10
6 CD34+ cells/kg was harvested on the fourth day of the mobilization. The autologous graft of the stem cells was cryopreserved and tested for the residual disease: the FISH revealed negative results and the RT-PCR was positive (BCR-ABL/ABL ratio 0,0017 in RQ-PCR). To our knowledge, this is the first report of successful PBSC harvest in a patient significantly pretreated with imatinib and nilotinib. [ABSTRACT FROM AUTHOR]- Published
- 2010
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153. Comparison of sequential versus myeloablative, reduced intensity and non-myleoablative conditioning for patients with myelodysplastic syndrome: An analysis of the CMWP of the EBMT
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Potter, Victoria, Wang, Jufeng, Ehninger, Gerhard, Auyk, Francis, Koster, Linda, Finke, Juergen, Beelen, Dietrich, Socie, Gerard, Ganser, Arnold, Sengeloev, Henrik, Labussiere-Wallet, Helene, Itala-Remes, Maija, Wreede, Lisbeth, Cascon, Marie, Jindra, Pavel, Mufti, Ghulam, Tischer, Johanna, Koe, Yener, Mutlu Arat, Bornhauser, Martin, Christopeit, Maximillian, Bertz, Hartmut, Steckel, Nina-Kristina, Kroeger, Nicolaus, and Robin, Marie
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Medizin
154. Measurable Residual Disease, FLT3-ITD Mutation And Disease Status Have Independent Prognostic Influence on Post-Transplant Outcomes in NPM1-Mutated Acute Myeloid Leukemia
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Al Hamed, Rama, Labopin, Myriam, Deconinck, Eric, Nuttyvuopio, Rutta, Huynh, Anne, Socie, Gerard, Yakoub-Agha, Ibrahim, Bourhis, Jean Henri, Naim, Hassan, Tholouli, Eleni, Choi, Goda, Poire, Xavier, Martin, Hans, Rubio, Marie-Therese, Jindra, Pavel, Didier Blaise, Beelen, Dietrich, Labussiere-Wallet, Helene, Esteve, Jordi, Nagler, Arnon, Bazarbachi, Ali, and Mohty, Mohamad
155. The Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: An Analysis By the EBMT Complications and Quality of Life WP
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Jagasia, Madan, Greinix, Hildegard T., Beohou, Eric, Werf, Steffie, Niederwieser, Dietger, Meijer, Ellen, Chevallier, Patrice, Sengeloev, Henrik, Blaise, Didier, Petersen, Eefke, Cornelissen, Jan J., Ehninger, Gerhard, Gribben, John G., Caballero, Dolores, Beguin, Yves, Michael Hallek, Jindra, Pavel, Fanin, Renato, Delage, Jeremy, Schoemans, Helene, Gedde-Dahl, Tobias, Nicolaus, Kroger, Basak, Grzegorz, and Duarte, Rafael F.
156. Allogeneic hematopoietic stem cell transplantation using HLA-compatible donors in younger high cytogenetic risk CLL patients results in very high long-term progression-free survival and may therefore favorably compete with sequential targeted therapy
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Gelder, Michel, Ziagkos, Dimitris, Wreede, Liesbeth, Biezen, Anja, Dreger, Peter, Gramatzki, Martin, Stelljes, Matthias, Andersen, Niels Smedegaard, Nicolaas Schaap, Vitek, Antonin, Beelen, Dietrich, Volin, Liisa, Finke, Juergen, Passweg, Jacob, Eder, Matthias, Machaczka, Maciej, Delgado, Julio, Krueger, William, Raida, Ludek, Socie, Gerard, Jindra, Pavel, Afanasyev, Boris, Wagner, Eva, Chalandon, Yves, Henseler, Anja, Schoenland, Stefan, Kroeger, Nicolaus, and Schetelig, Johannes
157. An EBMT Analysis of Matched Sibling, Mismatched Family or Matched Unrelated Donors for Allogeneic Stem Cell Transplants in MDS
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Raj, Kavita, Eikema, Diderik-Jan, Ehninger, Gerhard, Wolschke, Christine, Koster, Linda, Socie, Gerard, Finke, Juergen, Lint, Maria Teresa, Michallet, Mauricette, Ganser, Arnold, Volin, Liisa, Yener, Koc, Didier Blaise, Beelen, Dietrich W., Sengeloev, Henrik, Tischer, Johanna, Arat, Mutlu, Jindra, Pavel, Gulbas, Zafer, Pascual, Maria-Jesus, Ciceri, Fabio, Diez-Martin, Jose Luis, Robin, Marie, and Nicolaus, Kroger
158. External validation of scores predicting non-relapse mortality in patients with myelodysplastic syndrome: a study from MDS subcommittee of the CMWP EBMT
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Carre, Martin, Porcher, Raphael, Finke, Juergen, Ehninger, Gerhard, Koster, Linda, Beelen, Dietrich, Ganser, Arnold, Volin, Liisa, Lozano, Sara, Sengeloev, Henrik, Michallet, Mauricette, Tischer, Johanna, Olavarria, Eduardo, Pascual Cascon, Maria Jesus, Iacobelli, Simona, Koc, Yener, Jindra, Pavel, Mutlu Arat, Witte, Theo, Kroeger, Nicolaus, and Robin, Marie
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Medizin
159. Effectiveness of tixagevimab/cilgavimab in patients with hematological malignancies as a pre-exposure prophylaxis to prevent severe COVID-19: a Czech retrospective multicenter study.
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Demel, Ivo, Skopal, David, Šafránková, Eliška, Rozsívalová, Petra, Jindra, Pavel, Šrámek, Jiří, Turková, Adéla, Vydra, Jan, Labská, Klára, Vedrová, Jana, Čerňan, Martin, Szotkowski, Tomáš, Móciková, Heidi, Hynková, Lenka, Šušol, Ondrej, Kováčová, Ingrid, Belada, David, and Hájek, Roman
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SARS-CoV-2 , *PRE-exposure prophylaxis , *HIV seroconversion , *CORONAVIRUS diseases , *HEMATOPOIETIC stem cell transplantation , *HEMATOLOGIC malignancies , *SARS-CoV-2 Omicron variant - Abstract
Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies. [ABSTRACT FROM AUTHOR]
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- 2024
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160. An EBMT Analysis of Matched Sibling, Mismatched Family or Matched Unrelated Donors for Allogeneic Stem Cell Transplants in MDS
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Raj, Kavita, Eikema, Diderik-Jan, Ehninger, Gerhard, Wolschke, Christine, Koster, Linda, Socié, Gérard, Finke, Jürgen, Van Lint, Maria Teresa, Michallet, Mauricette, Ganser, Arnold, Volin, Liisa, Yener, Koc, Blaise, Didier, Beelen, Dietrich W, Sengeloev, Henrik, Tischer, Johanna, Arat, Mutlu, Jindra, Pavel, Gülbas, Zafer, Pascual, Maria-Jesús, Ciceri, Fabio, Díez-Martín, José Luis, Robin, Marie, and Nicolaus, Kroger
- Abstract
Introduction: MDS is the second most common indication for Allo HSCT exceeded only by AML. For patients with transfusion dependence, hypoplastic, fibrotic or high-risk MDS allogeneic stem cell transplantation is offered as a potential cure. Many patients are elderly and may have older siblings, co-morbidities and tolerate GVHD poorly. The availability of mismatched related (MMR) donors has been described in patients with MDS with small singe centre series suggesting that the lower levels of acute and chronic GVHD may make these a desirable donor. We therefore studied the MDS patients in the EBMT database (DB) to understand the effect of donor on outcomes.
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- 2017
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161. The Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: An Analysis By the EBMT Complications and Quality of Life WP
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Jagasia, Madan, Greinix, Hildegard T., Beohou, Eric, van der Werf, Steffie, Niederwieser, Dietger, Meijer, Ellen, Chevallier, Patrice, Sengeloev, Henrik, Blaise, Didier, Petersen, Eefke, Cornelissen, Jan J, Ehninger, Gerhard, Gribben, John G., Caballero, Dolores, Beguin, Yves, Hallek, Michael J., Jindra, Pavel, Fanin, Renato, Delage, Jeremy, Schoemans, Helene, Gedde-Dahl, Tobias, Nicolaus, Kroger, Basak, Grzegorz, and Duarte, Rafael F
- Abstract
Introduction:Rituximab (R), a CD20 monoclonal antibody, has been integrated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplants (HCT) in patients with B-cell malignancies, to decrease risk of recurrence. Single center data has suggested that R containing RIC regimens (R-RIC) may be associated with decreased chronic GVHD and better overall survival. We wanted to validate this finding in a larger registry cohort.
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- 2017
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162. Impact of In VivoT-Cell Depletion in Patients with Myelodysplastic Syndromes Undergoing Allogeneic Hematopoietic Stem Cell Transplant: A Registry Study from the Chronic Malignancies Working Party of the EBMT
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Forcade, Edouard, Chevret, Sylvie, Finke, Jürgen, Ehninger, Gerhard, Ayuk, Francis A, Beelen, Dietrich W, Koster, Linda, Ganser, Arnold, Socié, Gérard, Volin, Liisa, Sengeloev, Henrik, Michallet, Mauricette, Tischer, Johanna, Jindra, Pavel, Pascual, Maria-Jesús, Koc, Yener, Arat, Mutlu, de Witte, T. M. M, Kröger, Nicolaus, and Robin, Marie
- Abstract
Background: in vivo T-cell depletion (TCD) is frequently used in the setting of allogeneic hematopoietic stem cell in order to decrease acute and chronic GVHD incidence. Several randomized studies, enrolling patients with myeloid disease have concluded to a decreased risk of GVHD without increasing the relapse risk. The present study included only myelodysplastic syndrome patients and evaluated the impact of anti-thymoglobulin (ATG) or alemtuzumab on outcomes.
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- 2017
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163. THE ECONOMIC IMPACT OF GANCICLOVIR AND VALACYCLOVIR PROPHYLAXIS OF CYTOMEGALOVIRUS DISEASE IN RENAL TRANSPLANTATION.
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Reischig, Tomas, Opatrny Jr, Karel, Jindra, Pavel, Svecova, Miroslava, and Treska, Vladislav
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- 2006
164. Single and multiple point NRAS mutations in acute myeloid leukemia: a study of 327 well molecularly characterized patients.
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Durinikova, Anna, Folta, Adam, Pardy, Filip, Svaton, Jan, Drncova, Marie, Weinbergerova, Barbora, Cetkovsky, Petr, Racil, Zdenek, Jindra, Pavel, Szotkowski, Tomas, Zak, Pavel, Mayer, Jiri, and Jeziskova, Ivana
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ACUTE myeloid leukemia , *GENETIC mutation - Abstract
Similarly, nanopore analysis performed in 6/16 patients with simultaneously detected mutations in codons Gly12 and Gln61 or Gly13 and Gln61 did not reveal any patients with the presence of these mutations together on the same I NRAS i gene's allele. Oncogenic mutations in the I NRAS i gene are carried by 10-22% acute myeloid leukemia (AML) patients and represent one of the most commonly detected molecular aberrations in AML [[1], [3], [5]]. There was no significant difference in CR rate (89.5% vs. 75.0%, I p i = 0.2109), OS (33 months vs. undefined, I p i = 0.4300) or EFS (10 vs. 9 months, I p i = 0.6191) between patients with single I NRAS i mutation vs. patients with multiple I NRAS i mutations, respectively. NGS results from 5/16 patients with simultaneously detected multiple point mutations in codons Gly12 and Gly13 did not reveal any patients carrying these mutations on the same I NRAS i gene's allele. [Extracted from the article]
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- 2022
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165. Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy.
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Minarik, Jiri, Radocha, Jakub, Jungova, Alexandra, Straub, Jan, Jelinek, Tomas, Pika, Tomas, Pour, Ludek, Pavlicek, Petr, Harvanova, Lubica, Pospisilova, Lenka, Krhovska, Petra, Novakova, Denisa, Jindra, Pavel, Spicka, Ivan, Plonkova, Hana, Stork, Martin, Bacovsky, Jaroslav, Maisnar, Vladimir, and Hajek, Roman
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SMALL molecules , *PATIENT aftercare , *REPORTING of diseases , *THALIDOMIDE , *DEXAMETHASONE , *ANTINEOPLASTIC agents , *CANCER relapse , *TREATMENT effectiveness , *DESCRIPTIVE statistics , *MULTIPLE myeloma , *PROGRESSION-free survival , *ODDS ratio , *MEDICAL needs assessment , *PHARMACODYNAMICS - Abstract
Simple Summary: We report the final outomes of the addition of ixazomib to the combination of lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma in the routine clinical practice. With prolonged follow-up, the overall response rate was similar in both cohorts, but the addition of ixazomib induced more deeper responses. Median progression free survival was significantly better in patients receiving ixazomib and translated into better overal survival. Inferior results were seen in patients who were pretreated with lenalidomide in previous regimens. We conclude that the treatment using IRD regimen in routine practice is easy, well tolerated, and with very good therapeutic outcomes, comparable to the outcomes of the clinical trial. Background: We confirmed the benefit of addition of ixazomib to lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM) in unselected real-world population. We report the final analysis for overall survival (OS), second progression free survival (PFS-2), and the subanalysis of the outcomes in lenalidomide (LEN) pretreated and LEN refractory patients. Methods: We assessed 344 patients with RRMM, treated with IRD (N = 127) or RD (N = 217). The data were acquired from the Czech Registry of Monoclonal Gammopathies (RMG). With prolonged follow-up (median 28.5 months), we determined the new primary endpoints OS, PFS and PFS-2. Secondary endpoints included the next therapeutic approach and the survival measures in LEN pretreated and LEN refractory patients. Results: The final overall response rate (ORR) was 73.0% in the IRD cohort and 66.8% in the RD cohort. The difference in patients reaching ≥VGPR remained significant (38.1% vs. 26.3%, p = 0.028). Median PFS maintained significant improvement in the IRD cohort (17.5 vs. 12.5 months, p = 0.013) with better outcomes in patients with 1–3 prior relapses (22.3 vs. 12.7 months p = 0.003). In the whole cohort, median OS was for IRD vs. RD patients 40.9 vs. 27.1 months (p = 0.001), with further improvement within relapse 1-3 (51.7 vs. 27.8 months, p ˂ 0.001). The median PFS of LEN pretreated (N = 22) vs. LEN naive (N = 105) patients treated by IRD was 8.7 vs. 23.1 months (p = 0.001), and median OS was 13.2 vs. 51.7 months (p = 0.030). Most patients in both arms progressed and received further myeloma-specific therapy (63.0% in the IRD group and 53.9% in the RD group). Majority of patients received pomalidomide-based therapy or bortezomib based therapy. Significantly more patients with previous IRD vs. RD received subsequent monoclonal antibodies (daratumumab—16.3% vs. 4.3%, p = 0.0054; isatuximab 5.0% vs. 0.0%, p = 0.026) and carfilzomib (12.5 vs. 1.7%, p = 0.004). The median PFS-2 (progression free survival from the start of IRD/RD therapy until the second disease progression or death) was significantly longer in the IRD cohort (29.8 vs. 21.6 months, p = 0.016). There were no additional safety concerns in the extended follow-up. Conclusions: The IRD regimen is well tolerated, easy to administer, and with very good therapeutic outcomes. The survival measures in unsorted real-world population are comparable to the outcomes of the clinical trial. As expected, patients with LEN reatment have poorer outcomes than those who are LEN-naive. The PFS benefit of IRD vs. RD translated into significantly better PFS-2 and OS, but the outcomes must be accounted for imbalances in pretreatment group characteristics (especially younger age and stem cell transplant pretreatment), and in subsequent therapies. [ABSTRACT FROM AUTHOR]
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- 2022
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166. Outcome of allogeneic haematopoietic cell transplantation in eosinophilic disorders: A retrospective study by the chronic malignancies working party of the EBMT.
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McLornan, Donal P., Gras, Luuk, Martin, Ivonne, Sirait, Tiarlan, Schroeder, Thomas, Blau, Igor Wolfgang, Kuball, Jürgen, Byrne, Jenny, Collin, Matthew, Stadler, Michael, Desmier, Déborah, Salmenniemi, Urpu, Jindra, Pavel, Mikhailova, Natalia, Lenhoff, Stig, Rifón, Jose, Robin, Marie, Rovira, Montserrat, Veelken, Hendrik, and Sadowska‐Klasa, Alicja
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HYPEREOSINOPHILIC syndrome , *CELL transplantation , *GRAFT versus host disease - Abstract
Patients were transplanted with a median time to allo-HCT of 15.1 months (IQR, 9.8-27.9) for CEL, NOS patients, and 22.2 months (IQR, 11.5-55.8; I p i = 0.01) for HES. Helbig et al. reported on 10 patients with CEL, NOS with a median age of 62 (23-73 years), frequently with an aggressive clinical course, five of whom developed acute transformation within two years from the time of diagnosis.6 Here, only one patient in the chronic phase successfully underwent allo-SCT. Keywords: allogeneic stem cell transplant; chronic eosinophilic leukaemia; conditioning; hypereosinophilic syndrome; non-relapse mortality EN allogeneic stem cell transplant chronic eosinophilic leukaemia conditioning hypereosinophilic syndrome non-relapse mortality 209 213 5 06/27/22 20220701 NES 220701 Hypereosinophilic syndrome (HES) and chronic eosinophilic leukaemia (CEL), not otherwise specified (NOS) are rare haematological disorders.1 Allogeneic haematopoietic cell transplantation (allo-HCT) has been reported in single case reports or small case series only for both refractory HES or CEL, NOS and outcomes remain ill-defined.1-3 HES normally demonstrates a male predominance, likely underrecognized, with a variable clinical course. [Extracted from the article]
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- 2022
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167. Lymphocyte profile in peripheral blood of patients with multiple myeloma.
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Dekojová, Tereza, Gmucová, Hana, Macečková, Diana, Klieber, Robin, Ostašov, Pavel, Leba, Martin, Vlas, Tomáš, Jungová, Alexandra, Caputo, Valentina S., Čedíková, Miroslava, Lysák, Daniel, Jindra, Pavel, and Holubová, Monika
- Abstract
Multiple myeloma (MM) is a disease which remains incurable. One of the main reasons is a weakened immune system that allows MM cells to survive. Therefore, the current research is focused on the study of immune system imbalance in MM to find the most effective immunotherapy strategies. Aiming to identify the key points of immune failure in MM patients, we analysed peripheral lymphocytes subsets from MM patients (
n = 57) at various stages of the disease course and healthy individuals (HI,n = 15) focusing on T, NK, iNKT, B cells and NK-cell cytokines. Our analysis revealed that MM patients exhibited immune alterations in all studied immune subsets. Compared to HI, MM patients had a significantly lower proportion of CD4 + T cells (19.55% vs. 40.85%;p < 0.001) and CD4 + iNKT cells (18.8% vs. 40%;p < 0.001), within B cells an increased proportion of CD21LCD38L subset (4.5% vs. 0.4%;p < 0.01) and decreased level of memory cells (unswitched 6.1% vs. 14.7%;p < 0.001 and switched 7.8% vs. 11.2%; NS), NK cells displaying signs of activation and exhaustion characterised by a more than 2-fold increase in SLAMF7 MFI (p < 0.001), decreased expression of NKG2D (MFI) and NKp46 (%) on CD16 + 56 + and CD16 + 56- subset respectively (p < 0.05), Effective immunotherapy needs to consider these immune defects and monitoring of the immune status of MM patients is essential to define better interventions in the future. [ABSTRACT FROM AUTHOR]- Published
- 2024
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168. Measurable residual disease, FLT3-ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1-mutated acute myeloid leukemia.
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Al Hamed, Rama, Labopin, Myriam, Daguindau, Etienne, Niittyvuopio, Riitta, Huynh, Anne, Socié, Gerard, Srour, Micha, Bourhis, Jean Henri, Kröger, Nicolaus, Tholouli, Eleni, Choi, Goda, Poiré, Xavier, Martin, Hans, Rubio, Marie-Thérèse, Jindra, Pavel, Blaise, Didier, Beelen, Dietrich, Labussière-Wallet, Hélène, Nagler, Arnon, and Bazarbachi, Ali
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ACUTE myeloid leukemia , *STEM cell transplantation , *HEMATOPOIETIC stem cell transplantation , *KARNOFSKY Performance Status - Abstract
Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age ≥ 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow-up for survivors was 23.7 months. FLT3-ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia-free survival (LFS) were negatively affected by concomitant FLT3-ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p < 0.0001, respectively), MRD positivity at transplant (HR 2.18, p < 10-5 and HR 1.71, p < 10-5, respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score ≥90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3-ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p < 10-5), and older age (HR 1.22 per 10 years, p < 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score ≥90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3-ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1-mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions. [ABSTRACT FROM AUTHOR]
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- 2022
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169. The Replacement Mutation in HLA-DRB1*1211 Affects a Likely Keystone Position
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Horn, Peter A., DeLuca, David S., Jindra, Pavel, and Blasczyk, Rainer
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HLA histocompatibility antigens , *AMINO acids , *GENETIC mutation , *NUCLEOTIDES , *PEPTIDES - Abstract
Abstract: Currently, 10 different amino acid variants of the HLA-DRB1*12 family are known. We here report the identification of a new HLA-DRB1*12 allele in a healthy Caucasian male individual. The allele was detected by sequencing-based typing during confirmatory high-resolution typing of an unrelated, male, potential donor from the Czech National Marrow Donors Registry. Compared with DRB1*120101, to which it is closest, the new variant is characterized by a new replacement mutation (T→C) at nucleotide position 126 of exon 2, resulting in the amino acid substitution Phe→Leu at position 47. Computational analysis reveals that position 47 functions as a keystone in the β1 domain, joining both segments of the α helix with the β sheet, and plays a major role in the structural conformation of the binding groove. Additionally, position 47 is part of pocket E of the peptide binding groove and is directly involved in peptide binding. The new allele, DRB1*1211, is therefore likely to differ substantially from other DRB1*12 alleles in its peptide binding repertoire and alloreactive potential. [Copyright &y& Elsevier]
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- 2005
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170. Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice.
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Minarik, Jiri, Pika, Tomas, Radocha, Jakub, Jungova, Alexandra, Straub, Jan, Jelinek, Tomas, Pour, Ludek, Pavlicek, Petr, Mistrik, Martin, Brozova, Lucie, Krhovska, Petra, Machalkova, Katerina, Jindra, Pavel, Spicka, Ivan, Plonkova, Hana, Stork, Martin, Bacovsky, Jaroslav, Capkova, Lenka, Sykora, Michal, and Kessler, Petr
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MULTIPLE myeloma , *PROPORTIONAL hazards models , *PROGRESSION-free survival , *MONOCLONAL gammopathies , *DEXAMETHASONE - Abstract
Background: We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and refractory multiple myeloma (RRMM) in the routine clinical practice.Methods: A total of 344 patients treated with IRD (N = 127) or RD (N = 217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient's characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05.Results: In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval [CI] 0.51-0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0% in the IRD group vs 66.2% in the RD group with a complete response rate (CR) of 11.1% vs 8.8%, and very good partial response (VGPR) 22.2% vs 13.9%, IRD vs RD respectively. The IRD regimen was most beneficial in patients ≤75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable.Conclusions: Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting. [ABSTRACT FROM AUTHOR]- Published
- 2021
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171. Role of Age and Hematopoietic Cell Transplantation-Specific Comorbidity Index in Myelodysplastic Patients Undergoing an Allotransplant: A Retrospective Study from the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
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Carré, Martin, Porcher, Raphaël, Finke, Jürgen, Ehninger, Gerhard, Koster, Linda, Beelen, Dietrich, Ganser, Arnold, Volin, Liisa, Lozano, Sara, Friis, Lone, Michallet, Mauricette, Tischer, Johanna, Olavarria, Eduardo, Cascon, Maria Jesús Pascual, Iacobelli, Simona, Koc, Yener, Jindra, Pavel, Arat, Mutlu, de Witte, Theo, and Yakoub Agha, Ibrahim
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BLOOD groups , *HEMATOPOIETIC stem cell transplantation , *COMORBIDITY , *STEM cell transplantation , *ALEMTUZUMAB , *KARNOFSKY Performance Status , *BONE marrow - Abstract
• Allotransplant for myelodysplastic syndrome is limited by high nonrelapse mortality. • Comorbidities assessed by the original Sorror score impact mortality negatively. • Chronological age also continues to play an independent prognostic role on mortality. • Both age and comorbidities should be integrated in the allotransplant decision process. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option for myelodysplastic syndromes (MDSs) but is severely limited by nonrelapse mortality (NRM), especially in this mostly older population. Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). Moreover, the impact of age on NRM still remains a matter of debate. In recent years, the age at which transplants are made has been progressively increasing, and patients with comorbidities have become more common. Extricating the respective roles of age and comorbidities in toxic mortality is all the more important. This study by the European Group for Blood and Marrow Transplantation registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDSs between 2003 and 2014. Overall, 4-year NRM and overall survival were 32% and 47%, respectively. When considered as continuous predictors, HCT-CI score and age were associated with an increased hazard ratio (HR) for NRM. In multivariate analysis, age band (HR, 1.13; 95% CI, 1.02 to 1.25; P =.016), HCT-CI ≥3 (HR, 1.34; 95% CI, 1.04 to 1.73; P =.022), and Karnofsky Performance Status ≤80 (HR, 2.03; 95% CI, 1.52 to 2.73; P <.0001) were significantly predictive of a worse NRM. In our large cohort, both comorbidities, evaluated by the original HCT-CI score, and chronological age significantly affected NRM. Thus, age should be part of the transplant decision-making process and should be integrated in future scoring systems predicting outcomes of HSCT in MDSs. [ABSTRACT FROM AUTHOR]
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- 2020
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172. Allogeneic Stem Cell Transplantation for Blast Crisis Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: A Retrospective Study by the EBMT Chronic Malignancies Working Party.
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Radujkovic, Aleksandar, Dietrich, Sascha, Blok, Henric-Jan, Nagler, Arnon, Ayuk, Francis, Finke, Jürgen, Tischer, Johanna, Mayer, Jiri, Koc, Yener, Sorà, Federica, Passweg, Jakob, Byrne, Jenny L., Jindra, Pavel, Veelken, Joan Hendrik, Socié, Gerard, Maertens, Johan, Schaap, Nicolaas, Stadler, Michael, Itälä-Remes, Maija, and Tholouli, Eleni
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CHRONIC myeloid leukemia , *STEM cell transplantation , *PROTEIN-tyrosine kinases , *ALEMTUZUMAB , *PROTEIN-tyrosine kinase inhibitors , *KINASE inhibitors - Abstract
• Overall outcomes of patients allografted for BC CML remain poor in the TKI era. • Survival after alloSCT for BC CML depends on the pretransplant remission status. • Conventional prognostic factors remain outcome determinants for BC CML in remission. • UD transplant is associated with better LFS in patients with active BC at alloSCT. The prognosis of patients with blast crisis (BC) chronic myeloid leukemia (CML) is still dismal. Allogeneic stem cell transplantation represents the only curative treatment option, but data on transplant outcomes are scarce. We therefore conducted a retrospective, registry-based study of adult patients allografted for BC CML, focusing on patients with active disease at transplant and pretransplant prognostic factors. One hundred seventy patients allografted for BC CML after tyrosine kinase inhibitor pretreatment between 2004 and 2016 were analyzed. Before transplant, 95 patients were in remission, whereas 75 patients had active BC. In multivariable analysis of the entire cohort, active BC at transplant was the strongest factor associated with decreased overall survival (hazrd ratio, 1.87; P =.010) and shorter leukemia-free survival (LFS; hazard ratio, 1.69; P =.017). For patients with BC in remission at transplant, advanced age (≥45 years), lower performance status (≤80%), longer interval from diagnosis BC to transplant (>12 months), myeloablative conditioning, and unrelated donor (UD) transplant were risk factors for inferior survival. In patients with active BC, only UD transplant was significantly associated with prolonged LFS and trended toward improved overall survival. In summary, survival of patients allografted for BC CML was strongly dependent on pretransplant remission status. In patients with remission of BC, conventional prognostic factors remained the major determinants of outcome, whereas in those with active BC at transplant, UD transplant was associated with prolonged LFS in our study. [ABSTRACT FROM AUTHOR]
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- 2019
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173. Cryopreserved NK cells in the treatment of haematological malignancies: preclinical study.
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Holubova, Monika, Miklikova, Michaela, Leba, Martin, Georgiev, Daniel, Jindra, Pavel, Caprnda, Martin, Ciccocioppo, Rachele, Kruzliak, Peter, and Lysak, Daniel
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LEUKEMIA , *IMMUNE response , *CANCER immunotherapy , *KILLER cells , *CELL-mediated cytotoxicity - Abstract
Background: Leukaemia is an aggressive cancer of haematopoiesis. Despite increasing treatment success, the relapse rate is still high. Natural killer (NK) cells play a key role in the immune response to malignancies; thus, it is conceivable that NK cell-based immunotherapy may control relapses, while extending the disease-free survival. In our study, we investigated whether cryopreserved NK cells are able to kill the leukaemic K562 cell line, the necessity of IL-2 co-application and the association of activation marker expression (NKp44, NKG2D and CD25) with cytotoxic potential. Materials and methods: K562 cells were added to NK cell cultures in different ratios, i.e. 1:5, 1:10 and 1:20 (K562/NK), immediately after thawing NK cells or after 3-6-12-24 h of re-cultivation with or without IL-2. Results: Our results demonstrated the ability of cryopreserved NK cells to kill K562 in all ratios, times and culture conditions. The number of dead K562 cells depended on the number of NK cells and on the presence of IL-2. NK cells cytotoxic potential decreased gradually in the culture without IL-2. In contrast, NK cell-mediated cytotoxicity remained the same during the entire re-culture period after IL-2 re-application. Conclusion: Our study proved the efficacy of using cryopreserved ready-for-use NK cells in relapse treatment and the need for simultaneous administration of IL-2. [ABSTRACT FROM AUTHOR]
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- 2016
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174. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation.
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Schmid, Christoph, Labopin, Myriam, Socié, Gerard, Daguindau, Etienne, Volin, Liisa, Huynh, Anne, Bourhis, Jean Henri, Milpied, Noel, Cornelissen, Jan, Chevallier, Patrice, Maertens, Johan, Jindra, Pavel, Blaise, Didier, Lenhoff, Stig, Ifrah, Norbert, Baron, Frédéric, Ciceri, Fabio, Gorin, Claude, Savani, Bipin, and Giebel, Sebastian
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STEM cell transplantation , *ACUTE myeloid leukemia , *GRAFT versus host disease , *CANCER chemotherapy , *GENETIC mutation - Abstract
To analyze the influence of distinct combinations ofmolecular aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for cytogenetically normal acute myeloid leukemia (CN-AML), a retrospective registry analysis was performed on 702 adults undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1mut) and FLT3 internal tandem duplications (FLT3-ITD). Double-negative patients were evaluated for mutations of the CCAAT/enhancer binding protein a gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. Two-year OS fromHSCTwas 81 ± 5% in NPM1mut/FLT3wt, 75 ± 3% in NPM1wt/FLT3wt, 66 ± 3% in NPM1mut/ FLT3-ITD, and 54 ± 7% in NPM1wt/FLT3-ITD (P = .003). Analysis of CEBPα among patients with NPM1wt/FLT3wt revealed excellent results both in patients with CEBPαmut and with atriple negative genotype(2-year OS:100%/77 ± 3%). In aCox-model of predefined variables, age, FLT3-ITD and >1 course of chemotherapy to reach CR were risk factors associated with inferior outcome, regardless of NPM1 mutational status, variations of transplant protocols, or development of graft-versus-host disease. In a prognostic risk classification, 2-year OS/LFS rates were 88 ± 3%/79 ± 4% without any, 77 ± 2%/73 ± 3% with one, and 53 ± 4%/50 ± 4 with ≥2 risk factors (P = .003/.002). [ABSTRACT FROM AUTHOR]
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- 2015
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175. HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation.
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Petersdorf, Effie W., Gooley, Theodore A., Malkki, Mari, Bacigalupo, Andrea P., Cesbron, Anne, Toit, Ernette Du, Ehninger, Gerhard, Egeland, Torstein, Fischer, Gottfried F., Gervais, Thibaut, Haagenson, Michael D., Horowitz, Mary M., Hsu, Katharine, Jindra, Pavel, Madrigal, Alejandro, Oudshoorn, Machteld, Ringdén, Olle, Schroeder, Marlis L., Spellman, Stephen R., and Tiercy, Jean-Marie
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HEMATOPOIETIC stem cell transplantation , *ORGAN donors , *IMMUNE response , *IMMUNOGLOBULIN allotypes , *DISEASE relapse - Abstract
Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease. [ABSTRACT FROM AUTHOR]
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- 2014
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176. High-dose therapy and autologous stem cell transplantation in marginal zone lymphomas: A retrospective study by the EBMT Lymphoma Working Party and FIL-GITMO
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Virginia Valeria Ferretti, Christof Scheid, Frank Kroschinsky, Ariane Boumendil, Gerhard Held, Denis Caillot, Björn E. Wahlin, Norbert Ifrah, Jean Bourhis, Mohammed Wattad, Maurizio Musso, David Pohlreich, Catherine Thieblemont, Peter Dreger, Pavel Jindra, Emmanuelle Nicolas-Virelizier, Anette Haenel, Irit Avivi, Martin Gramatzki, Blaise Didier, Silvia Montoto, Giuseppe Milone, Devizzi Liliana, Christian Berthou, Luca Arcaini, François Guilhot, Emmanuel Bachy, Francesco Zaja, Annarita Conconi, Herve Finel, Avivi, Irit, Arcaini, Luca, Ferretti, Virginia V., Boumendil, Ariane, Finel, Hervé, Milone, Giuseppe, Zaja, Francesco, Liliana, Devizzi, Musso, Maurizio, Didier, Blaise, Bachy, Emmanuel, Wattad, Mohammed, Nicolas-Virelizier, Emmanuelle, Gramatzki, Martin, Bourhis, Jean-Henri, Caillot, Deni, Haenel, Anette, Held, Gerhard, Thieblemont, Catherine, Jindra, Pavel, Pohlreich, David, Guilhot, Françoi, Kroschinsky, Frank, Wahlin, Björn, Scheid, Christof, Ifrah, Norbert, Berthou, Christian, Dreger, Peter, Montoto, Silvia, Conconi, Annarita, Tel Aviv Sourasky Medical Center [Te Aviv], Division of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Lymphoma Working Party, Paris (EBMT), Oncohematology Unit, Oncology Department La Maddalena, Centre Léon Bérard [Lyon], 2nd Medical Department, University Hospital Schleswig-Holstein Campus Kiel, Division of Stem Cell Transplantation and, Institut Gustave Roussy (IGR), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Instituto de Pesquisas Meteorológicas (IPMet), Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Department of Hematology and Oncology [Pilsen, Czech Republic], Charles University Hospital Pilsen, Charles University Hospital, CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department I of Internal Medicine, University of Cologne, Hematology Department, Université d'Angers (UA), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Department of Medicine V, Universität Heidelberg [Heidelberg], AOU Maggiore della Carità, Division of Hematology, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Universidade Estadual Paulista Júlio de Mesquita Filho [São José do Rio Preto] (UNESP), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Autologous transplant ,[SDV]Life Sciences [q-bio] ,Transplantation, Autologous ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,Chemoimmunotherapy ,Marginal zone lymphoma ,Mucosa-associated lymphoid tissue lymphoma ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cumulative incidence ,Treatment Failure ,Retrospective Studies ,business.industry ,Hematopoietic Stem Cell Transplantation ,MALT lymphoma ,Lymphoma, B-Cell, Marginal Zone ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,3. Good health ,Lymphoma ,Transplantation ,Regimen ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Rituximab ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
IF 5.128; International audience; The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non‐transformed nodal, extra‐nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111 MALT lymphoma, 55 nodal MZL (NMZL) and 33 SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1–8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy‐based high‐dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in the MALT sub‐group and more transplants performed in recent years in the other sub‐groups. After a median follow‐up of 5 years, 5‐year cumulative incidence of relapse/progression and non‐relapse mortality were 38% and 9%, respectively. Five‐year event‐free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five‐year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorter EFS and OS. In addition, patients with SMZL had a shorter OS than those with MALT. ASCT may provide clinical benefit in MZL patients who have failed multiple lines of chemoimmunotherapy.
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- 2018
177. Incidence and outcome of central nervous system relapse after hematopoietic stem cell transplantation in patients suffering from acute myeloid leukemia and acute lymphoblastic leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Blum S, Chalandon Y, Labopin M, Finke J, Gedde-Dahl T, Othman TB, Cornelissen JJ, Jindra P, Labussière-Wallet H, Collin M, Lenhoff S, Kobbe G, Gutiérrez NC, Nagler A, and Mohty M
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- Humans, Incidence, Male, Adult, Female, Middle Aged, Adolescent, Europe epidemiology, Recurrence, Young Adult, Treatment Outcome, Aged, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma epidemiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Central Nervous System Neoplasms therapy
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- 2024
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178. Current knowledge about FLT3 gene mutations, exploring the isoforms, and protein importance in AML.
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Macečková D, Vaňková L, Holubová M, Jindra P, Klieber R, Jandová E, and Pitule P
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- Humans, Protein Isoforms genetics, Cell Survival, Mutation genetics, Protein-Tyrosine Kinases, fms-Like Tyrosine Kinase 3 genetics, Leukemia, Myeloid, Acute genetics
- Abstract
Acute myeloid leukaemia (AML) is a complex haematological malignancy characterised by diverse genetic alterations leading to abnormal proliferation of myeloid precursor cells. One of the most significant genetic alterations in AML involves mutations in the FLT3 gene, which plays a critical role in haematopoiesis and haematopoietic homeostasis. This review explores the current understanding of FLT3 gene mutations and isoforms and the importance of the FLT3 protein in AML. FLT3 mutations, including internal tandem duplications (FLT3-ITD) and point mutations in the tyrosine kinase domain (FLT3-TKD), occur in 25-30% in AML and are associated with poor prognosis. FLT3-ITD mutations lead to constitutive activation of the FLT3 signalling pathway, promoting cell survival and proliferation. FLT3-TKD mutations affect the tyrosine kinase domain and affect AML prognosis in various ways. Furthermore, FLT3 isoforms, including shorter variants, contribute to the complexity of FLT3 biology. Additionally, nonpathological polymorphisms in FLT3 are being explored for their potential impact on AML prognosis and treatment response. This review also discusses the development of molecular treatments targeting FLT3, including first-generation and next-generation tyrosine kinase inhibitors, highlighting the challenges of resistance that often arise during therapy. The final chapter describes FLT3 protein domain rearrangements and their relevance to AML pathogenesis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2024
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179. De novo accelerated phase of chronic myeloid leukemia should be recognized even in the era of tyrosine kinase inhibitors.
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Hornak T, Mayer J, Cicatkova P, Semerad L, Kvetkova A, Klamova H, Faber E, Belohlavkova P, Karas M, Stejskal L, Cmunt E, Cerna O, Srbova D, Zizkova H, Vrablova L, Skoumalova I, Voglova J, Jurkova T, Chrapava M, Jurcek T, Jeziskova I, Jarosova M, Machova Polakova K, Papajik T, Zak P, Jindra P, and Zackova D
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- Humans, Blast Crisis drug therapy, Protein Kinase Inhibitors therapeutic use, Tyrosine Kinase Inhibitors, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Abstract
Overall survival of patients classified according to the European LeukemiaNet 2020 classification. Chronic phase (CP), accelerated phase (AP), blast crisis (BC), low risk (LR), intermediate risk (IR), high risk (HR)., (© 2024 Wiley Periodicals LLC.)
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- 2024
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180. Why are not all eligible chronic myeloid leukemia patients willing to attempt tyrosine kinase inhibitor discontinuation? A Czech nationwide analysis related to the TKI stopping trial HALF.
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Žáčková D, Semerád L, Faber E, Klamová H, Stejskal L, Bělohlávková P, Karas M, Cmunt E, Černá O, Procházková J, Čičátková P, Kvetková A, Horňák T, Skoumalová I, Srbová D, Šálek C, Buffa D, Voglová J, Jurček T, Folta A, Ježíšková I, Žižková H, Machová Poláková K, Papajík T, Žák P, Jindra P, Svobodník A, Štěpánová R, and Mayer J
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- Humans, Tyrosine Kinase Inhibitors, Czech Republic, Chronic Disease, Protein Kinase Inhibitors therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myeloid
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- 2024
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181. Current use of fecal microbiota transfer in patients with hematologic diseases: a survey on behalf of the Cellular Therapy and Immunobiology Working Party of the EBMT.
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Battipaglia G, Mooyaart JE, Meyer R, Mohty M, Sadowska-Klasa A, Goloshchapov O, Locatelli F, Styczynski J, Pavlu J, Dybko J, Bronin G, Salmenniemi U, Jindra P, Hoogenboom JD, Kuball J, Ruggeri A, and Malard F
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- Humans, Fecal Microbiota Transplantation, Surveys and Questionnaires, Hematopoietic Stem Cell Transplantation, Hematologic Diseases therapy
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- 2023
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182. The European landscape on allogeneic haematopoeietic cell transplantation in Chronic Lymphocytic Leukaemia between 2009 and 2019: a perspective from the Chronic Malignancies Working Party of the EBMT.
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Tournilhac O, van Gelder M, Eikema DJ, Zinger N, Dreger P, Bornhäuser M, Vucinic V, Scheid C, Cornelissen JJ, Schroeder T, Jindra P, Sengeloev H, Nguyen Quoc S, Stelljes M, Blau IW, Mayer J, Paneesha S, Chevallier P, Forcade E, Kröger N, Blaise D, Gribben J, Nielsen B, Johansson JE, Kyriakou C, Beguin Y, Pioltelli P, Sampol A, McLornan DP, Schetelig J, Hayden PJ, and Yakoub-Agha I
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- Humans, Neoplasm Recurrence, Local, Transplantation, Homologous methods, Transplantation Conditioning methods, Retrospective Studies, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Hematopoietic Stem Cell Transplantation methods, COVID-19 etiology
- Abstract
Allogeneic transplantation (allo-HCT) is a curative treatment in CLL whose efficacy including the most severe forms had led to the 2006 EBMT recommendations. The advent after 2014 of targeted therapies has revolutionized CLL management, allowing prolonged control to patients who have failed immunochemotherapy and/or have TP53 alterations. We analysed the pre COVID pandemic 2009-2019 EBMT registry. The yearly number of allo-HCT raised to 458 in 2011 yet dropped from 2013 onwards to an apparent plateau above 100. Within the 10 countries who were under the EMA for drug approval and performed 83.5% of those procedures, large initial differences were found but the annual number converged to 2-3 per 10 million inhabitants during the 3 most recent years suggesting that allo-HCT remains applied in selected patients. Long-term follow-up on targeted therapies shows that most patients relapse, some early, with risk factors and resistance mechanisms being described. The treatment of patients exposed to both BCL2 and BTK inhibitors and especially those with double refractory disease will become a challenge in which allo-HCT remains a solid option in competition with emerging therapies that have yet to demonstrate their long-term effectiveness., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2023
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183. Autologous versus allogeneic hematopoietic cell transplantation for older patients with acute lymphoblastic leukemia. An analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Giebel S, Labopin M, Houhou M, Caillot D, Finke J, Blaise D, Fegueux N, Ethell M, Cornelissen JJ, Forcade E, Yakoub-Agha I, Lussana F, Maertens J, Bourhis JH, Jindra P, Gorin NC, Nagler A, and Mohty M
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- Aged, Humans, Retrospective Studies, Bone Marrow, Prospective Studies, Transplantation, Homologous methods, Acute Disease, Recurrence, Transplantation Conditioning methods, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Graft vs Host Disease etiology
- Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) with reduced intensity conditioning (RIC) is an option for elderly patients with acute lymphoblastic leukemia (ALL). We retrospectively compared results of RIC-allo-HCT from either a matched sibling donor (MSD, n = 209) or matched unrelated donor (MUD, n = 209) with autologous (auto, n = 142) HCT for patients aged 55 years or more treated in first complete remission (CR1) between 2000 and 2018. The probabilities of leukemia-free survival (LFS) at 5 years were 34% for RIC-allo-HCT versus 39% for auto-HCT (p = 0.11) while overall survival (OS) rates were 42% versus 45% (p = 0.23), respectively. The incidence of relapse (RI) and non-relapse mortality (NRM) was 41% versus 51% (p = 0.22) and 25% versus 10% (p = 0.001), respectively. In a multivariate model, using auto-HCT as reference, the risk of NRM was increased for MSD-HCT (Hazard ratio [HR] = 2.1, p = 0.02) and MUD-HCT (HR = 3.08, p < 0.001), which for MUD-HCT translated into a decreased chance of LFS (HR = 1.55, p = 0.01) and OS (HR = 1.62, p = 0.008). No significant associations were found with respect to the risk of relapse. We conclude that for patients with ALL in CR1, aged above 55 years, auto-HCT may be considered a transplant option alternative to RIC-allo-HCT, although its value requires verification in prospective trials., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2023
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184. Allogeneic stem cell transplantation in patients with multiple myeloma-single center experience.
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Kříž T, Jungová A, Lysák D, Karas M, Hrabětová M, Šrámek J, and Jindra P
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- Humans, Adult, Middle Aged, Retrospective Studies, Quality of Life, Neoplasm Recurrence, Local, Stem Cell Transplantation adverse effects, Transplantation Conditioning adverse effects, Disease-Free Survival, Treatment Outcome, Multiple Myeloma therapy, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease
- Abstract
The standard of care in multiple myeloma (MM) consists of induction chemotherapy followed by autologous stem cell transplant (autoSCT), but this setting doesn't present curative potential. Despite advances in new, efficient, and targeted drugs, allogeneic transplant (aloSCT) remains the modality with curative potential in MM. With the knowledge of high mortality and morbidity related to the treatment in comparison to treatment with novel drugs, there is no consensus in the indication of aloSCT in MM, also the choice of ideal patients profiting from this method is difficult. Therefore, we performed a retrospective unicentric study of 36 unselected consecutive patients transplanted for MM in the University Hospital in Pilsen between the years 2000-2020 in order to define possible variables influencing survival. The median age of the patients was 52 years (38-63) and the distribution of MM subtypes was standard. The majority of the patients were transplanted in the relapse setting, 3 (8.3%) patients in the 1st line setting, and in 7 (19%) patients elective auto-alo tandem transplant was performed. 18 patients (60% of patients with available cytogenetics (CG) had high-risk disease. 12 (33.3%) patients were transplanted with chemoresistant disease (at least PR not reached). With a median follow-up of 85 months, we observed median overall survival (OS) of 30 months (range 10-60) and median progression-free survival (PFS) of 15 months (11-175). 1- and 5-year Kaplan Meier survival probabilities for OS were 55% and 30.5% respectively. During the follow-up, 27 (75%) patients died, 11 (35%) due to treatment-related mortality (TRM), and 16 patients (44%) due to a relapse. 9 (25%) patients were still alive, 3 (8.3%) of them with complete remission (CR), and 6 (16.7%) patients with relapse/progression. Altogether 21 (58%) of the patients relapsed/progressed with a median of 11 months (3-175). Incidence of clinically significant acute graft versus host disease (aGvHD gr. >II) was low (8.3%) and extensive chronic GvHD (cGvHD) developed in 4 patients (11.1%). Univariant analysis proved marginal statistical significance in disease status before aloSCT (chemosensitive × chemoresistant) for OS, favoring patients with the chemosensitive disease (HR 0.43, 95% CI 0.18-1.01, p=0.05), there was no significant impact of high-risk cytogenetics (CG) on survival. No other analyzed parameter was found to be significant. Our findings support the conclusion that aloSCT is able to overcome high-risk CG and that aloSCT still remains a valid treatment choice with acceptable toxicity in well-selected high-risk patients with curative potential, even though often with active disease, but not derogating the quality of life significantly.
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- 2023
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185. Determinants of refined GvHD-free, relapse-free survival after reduced-intensity allogeneic hematopoietic cell transplantation in older patients with myeloid malignancies.
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Jindra P, Karas M, Lysák D, Šrámek J, Steinerová K, Hrabětová M, and Jungová A
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- Humans, Aged, Middle Aged, Retrospective Studies, Transplantation, Homologous adverse effects, Neoplasm Recurrence, Local, Transplantation Conditioning, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute, Myeloproliferative Disorders complications, Graft vs Host Disease etiology
- Abstract
Background: Older patients with AML/MDS have a poor prognosis with alloHCT as the only curative option. However alloHCT is challenging given its high TRM. Recently, a composite endpoint of GRFS was proposed to define transplant success. A single centre retrospective analysis was performed to determine the main variables influencing GRFS., Patients and Methodsmethods: 91 consecutive patients≥ 60 years (median 64 years, range 60-74) with AML/MDS who received reduced-intensity alloHCT during 2001-2017 analysed. Disease risk index (DRI) at HCT was low/intermediate in 47pts (52%) and high in 44 pts (48%)., Results: After median follow-up for survivors of 56 months (range 7-144), 37 (40.6%) patients were alive. The OS, LFS and GRFS were 61.4%, 58.1%, 49.1% at 1 year and 35.5%, 32.3% and 23.1% at 5 years, respectively. The 1-year and 5-year incidences of NRM and relapse were 26.9%, 21.3% and 47.9% and 35.4%, respectively. In univariate analysis, high DRI was the strongest factor for worse OS (HR 2.121; p = 0.049), LFS (HR 1.924; p = 0.0123) and GRFS (HR 2.319; p = 0.0005). The donor age ≥ 62 years had a negative impact on OS (HR 2.110; p = 0.0345) and GRFS (HR 2.014; p = 0.0341). High DRI (HR 2.652; p = 0.0003) and donor age (HR 2.304; p = 0.0257) retained its significance in multivariate analysis for GRFS., Conclusion: A significant portion of older patients with myeloid malignancies survive alloHCT without experiencing GRFS event with DRI as the main determinant of outcome. Negative impact of donor age≥ 62 years suggests preference of a young donor, regardless of being related or unrelated., Competing Interests: Declarations of interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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186. Current possibilities and risks of donating some tissues, cells, and organs from living donors.
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Konečná H, Čermáková Z, Honzová I, Chmel R, Jindra P, Krbcová J, Navrátilová J, Pastor Z, Turek P, and Větrovcová H
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- Humans, Living Donors psychology, Tissue and Organ Harvesting adverse effects
- Abstract
Transfusion, transplantation, and regenerative medicine are rapidly developing fields. The authors of the text want to inform about upcoming legislative changes at the EU level and briefly describe and compare the difficulty of some donation procedures from the point of view of a living donor, as well as their risks, including psychosocial risks. The study is based on a qualitative expert investigation. Comparing the complexity of procedures from the perspective of donors is important, for example, for setting compensations. The tables show that the current compensations are disproportionate.
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- 2023
187. COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA).
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Marchesi F, Salmanton-García J, Emarah Z, Piukovics K, Nucci M, López-García A, Ráčil Z, Farina F, Popova M, Zompi S, Audisio E, Ledoux MP, Verga L, Weinbergerová B, Szotkovski T, Da Silva MG, Fracchiolla N, De Jonge N, Collins G, Marchetti M, Magliano G, García-Vidal C, Biernat MM, Van Doesum J, Machado M, Demirkan F, Al-Khabori M, Žák P, Víšek B, Stoma I, Méndez GA, Maertens J, Khanna N, Espigado I, Dragonetti G, Fianchi L, Del Principe MI, Cabirta A, Ormazabal-Vélez I, Jaksic O, Buquicchio C, Bonuomo V, Batinić J, Omrani AS, Lamure S, Finizio O, Fernández N, Falces-Romero I, Blennow O, Bergantim R, Ali N, Win S, Van Praet J, Tisi MC, Shirinova A, Schönlein M, Prattes J, Piedimonte M, Petzer V, Navrátil M, Kulasekararaj A, Jindra P, Sramek J, Glenthøj A, Fazzi R, De Ramón-Sánchez C, Cattaneo C, Calbacho M, Bahr NC, El-Ashwah S, Cordoba R, Hanakova M, Zambrotta G, Sciumè M, Booth S, Rodrigues RN, Sacchi MV, García-Poutón N, Martín-González JA, Khostelidi S, Gräfe S, Rahimli L, Ammatuna E, Busca A, Corradini P, Hoenigl M, Klimko N, Koehler P, Pagliuca A, Passamonti F, Cornely OA, and Pagano L
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- Humans, Adult, Follow-Up Studies, COVID-19 Testing, COVID-19, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute drug therapy, Hematology
- Abstract
Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.
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- 2023
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188. Correction: Comparison of HLA-mismatched unrelated donor transplantation with post-transplant cyclophosphamide versus HLA-haploidentical transplantation in patients with active acute myeloid leukemia.
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Baron F, Labopin M, Tischer J, Ciceri F, Raiola AM, Blaise D, Sica S, Vydra J, Fanin R, Diez-Martin JL, Bulabois CE, Stölzel F, Busca A, Jindra P, Koc Y, Chevallier P, Forcade E, Rösler W, Passweg J, Kulagin A, Carella AM, Simand C, Bazarbachi A, Pioltelli P, Nagler A, and Mohty M
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- 2022
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189. Comparison of HLA-mismatched unrelated donor transplantation with post-transplant cyclophosphamide versus HLA-haploidentical transplantation in patients with active acute myeloid leukemia.
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Baron F, Labopin M, Tischer J, Ciceri F, Raiola AM, Blaise D, Sica S, Vydra J, Fanin R, Diez-Martin JL, Bulabois CE, Stölzel F, Busca A, Jindra P, Koc Y, Chevallier P, Forcade E, Rösler W, Passweg J, Kulagin A, Carella AM, Simand C, Bazarbachi A, Pioltelli P, Nagler A, and Mohty M
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- Adult, Humans, Transplantation, Haploidentical adverse effects, Unrelated Donors, Transplantation Conditioning methods, Retrospective Studies, Cyclophosphamide therapeutic use, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute drug therapy
- Abstract
HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) is frequently used as treatment for patients with active acute myeloid leukemia (AML). Here, we investigated whether 9/10 HLA-mismatched unrelated donor transplantation (MMUD-HCT) with post-transplant cyclophosphamide (PTCy) is an adequate alternative. Inclusion criteria in this retrospective registry study consisted of adult patients, first HCT with a Haplo donor or MMUD between 2010 and 2020 using PTCy as graft-versus-host disease (GVHD) prophylaxis, and primary refractory or relapsed disease. MMUD patients were pair-matched 1 to 2 with Haplo-recipients. A total of 73 MMUD patients met the inclusion criteria. Their data were compared to those of 146 Haplo patients in a matched-pair analysis. Median follow-up was 27 months in MMUD patients and 36 months in Haplo recipients. Two-year incidences of relapse and non-relapse mortality (NRM) were 40% and 18% in MMUD patients, respectively, versus 50% (P = 0.23) and 24% (P = 0.18) in Haplo recipients. Two-year leukemia-free survival (LFS) and overall survival (OS) was 42% and 46% in MMUD recipients, respectively, versus 26% (P = 0.1) and 28% (P = 0.061) in Haplo-patients. In conclusions, in AML patients with active disease at transplantation, MMUD-HCT results in at least comparable outcomes to Haplo-HCT when PTCy is applied., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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190. Impact of Cytogenetic Risk on Outcomes of Non-T-Cell-Depleted Haploidentical Hematopoietic Cell Transplantation in Patients with Relapsed or Refractory Acute Myeloid Leukemia.
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Nagler A, Labopin M, Dholaria B, Ciceri F, Fraccaroli A, Blaise D, Fanin R, Bruno B, Forcade E, Vydra J, Chevallier P, Bulabois CE, Jindra P, Bornhäuser M, Canaani J, Sanz J, Savani BN, Spyridonidis A, Giebel S, Brissot E, Bazarbachi A, Esteve J, and Mohty M
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- Humans, Transplantation, Haploidentical, Recurrence, Chronic Disease, Cytogenetic Analysis, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute genetics, Graft vs Host Disease
- Abstract
Baseline cytogenetics and disease status are key factors predicting the outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with acute myeloid leukemia (AML). The importance of cytogenetic risk in patients with primary refractory or relapsed (R/R) AML undergoing haploidentical (Haplo) HCT is unknown. We studied the impact of cytogenetic risk in patients with R/R de novo AML with active disease who underwent non-T-cell-depleted Haplo-HCT with post-transplantation cyclophosphamide from 2010 to 2020. Four hundred forty patients with active disease at transplantation from the European Society for Blood and Marrow Transplantation database were analyzed (291 [66.1%] with intermediate-risk [AMLint] and 149 [44.1%] with adverse-risk cytogenetics [AMLadv]). Impact of baseline cytogenetic risk on various transplantation outcomes was evaluated. Pre-transplantation disease status was relapse in 48.1% and 26.8% and primary refractory in 51.9% and 73.2% of the patients with AMLint and AMLadv, respectively (P < .0001). Two-year leukemia-free survival (LFS, 35.5% versus 15.5%, P = .001) and overall survival (OS, 39.2% versus 20.1%, P = .001) were better in AMLint versus AMLadv. In multivariate analysis, the relapse rate was significantly higher (hazard ratio [HR] = 2.17 [95% confidence interval {CI} 1.57-3.0]) and LFS (HR = 1.71 [95% CI, 1.31-2.22]) and OS (HR = 1.69 [95% CI, 1.29-2.22]), significantly lower for patients with AMLadv compared to AMLint, conditioning intensity did not affect leukemia relapse rate. Non-relapse mortality (HR = 1.1 [95% CI, 0.7-1.74]) and graft-versus-host disease-free, relapse-free survival (HR = 1.37 [95% CI, 1.06-1.77]) did not differ significantly between the risk groups. Disease status before transplant (primary refractory versus relapsed) or conditioning intensity did not impact main transplant outcomes. Baseline cytogenetic risk remains a key prognostic factor for patients with R/R AML with persistent disease before non-T-cell-depleted Haplo-HCT., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2022
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191. Impact of in vivo T-cell depletion in patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplant: a registry study from the Chronic Malignancies Working Party of the EBMT.
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Forcade E, Chevret S, Finke J, Ehninger G, Ayuk F, Beelen D, Koster L, Ganser A, Volin L, Sengeloev H, Michallet M, Tischer J, Jindra P, Cascon MJP, Koc Y, Arat M, Tomaszewska A, Hayden P, de Witte T, Yakoub-Agha I, Kröger N, and Robin M
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- Alemtuzumab therapeutic use, Humans, Recurrence, Registries, Retrospective Studies, T-Lymphocytes, Transplantation Conditioning adverse effects, Transplantation, Homologous adverse effects, Treatment Outcome, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes therapy, Neoplasms complications
- Abstract
While in vivo T-cell depletion (TCD) is widely used, its benefit in patients with MDS still remains a matter of debate. This study evaluates the impact of TCD on outcomes, and compares ATG and alemtuzumab, in patients with MDS. 1284 patients from the EBMT registry were included in this study with 470 patients in the no-TCD group and 814 in the TCD group (alemtuzumab N = 168; ATG N = 646). At 6 months, aGVHD III-IV cumulative incidences (CI) for no-TCD, ATG or alemtuzumab groups were 13% vs 14% vs 11% (ns), respectively. At 5 years, CI of chronic GVHD were 64% vs 52% vs 51% (p < 0.00017); and CI of relapse was 23% vs 25% vs 39% (p < 0.0001) for no TCD, ATG and alemtuzumab respectively; OS was 47% vs 46% vs 34% (p = 0.009) respectively; and GRFS was 21% vs 28% and 20% (p = 0.045) respectively. In multivariable analysis, ATG improved GRFS, and alemtuzumab decreased OS. Both ATG and alemtuzumab decreased risk of chronic GVHD, but the increased risk of relapse with alemtuzumab is associated with a poor GRFS and suggest to not use alemtuzumab in the setting of allo-SCT for high risk disease., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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192. Successful early use of anti-SARS-CoV-2 monoclonal neutralizing antibodies in SARS-CoV-2 infected hematological patients - A Czech multicenter experience.
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Weinbergerová B, Demel I, Víšek B, Válka J, Čerňan M, Jindra P, Novák J, Stejskal L, Kovácsová F, Kabut T, Szotkowski T, Hájek R, Žák P, Cetkovský P, Král Z, and Mayer J
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- Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing, COVID-19 Testing, Czech Republic, Humans, Immunization, Passive, Prospective Studies, COVID-19 Serotherapy, COVID-19 therapy, SARS-CoV-2, COVID-19 Drug Treatment
- Abstract
COVID-19 significantly impairs survival rates among hematological patients when compared to the general population. Our prospective multicentre project analyzed early administration of anti-SARS-CoV-2 spike protein neutralizing monoclonal antibodies (NmAbs) - bamlanivimab (72%) and casirivimab/imdevimab (28%) - efficacy among hematological patients with early-stage COVID-19. Mortality rate was compared to a control cohort of 575 SARS-CoV-2 positive hematological patients untreated with any specific anti-COVID-19 therapy. 88 hematological patients with lymphomas, acute leukemias, and myeloma as their most frequent underlying diagnoses (72%) were evaluated with a 97 days median follow-up after NmAb administration. One third of patients (32%) were treated with an anti-CD20 monoclonal antibody before COVID-19 diagnosis. Median time between first COVID-19 symptom and NmAb administration was 2 days. When administering NmAb, 29%, 57%, 11%, 2%, and 1% of our patients had asymptomatic, mild, moderate, severe, and critical degrees of COVID-19, respectively. 80% of baseline asymptomatic patients remained asymptomatic following NmAb administration. Median duration of COVID-19 symptoms after NmAb administration was 2.5 days. Progression to severe/critical COVID-19 occurred among a total of 17% (15/88) of our cases and numerically higher with bamlanivimab versus casirivimab/imdevimab (21% vs. 8%; p = 0.215), and myelomas (29%), lymphomas (17%) and acute leukemias (18%), respectively. During final follow-up, nine deaths (10%) were recorded - all after bamlanivimab (p = 0.056) with 8% attributed to COVID-19. Regarding "remdesivir/convalescent plasma naïve" patients, COVID-19 mortality rates were significantly lower in our NmAbs treated cohort compared to the control cohort of untreated SARS-CoV-2 positive hematological patients (6% vs. 16%, p = 0.020), respectively. Our study validated the safety and efficacy of NmAbs early use among hematological patients with newly diagnosed early-stage COVID-19 in terms of alleviating infection course and decreasing mortality. Results confirmed a more positive effect of a casirivimab/imdevimab combination versus bamlanivimab monotherapy., (© 2022 John Wiley & Sons Ltd.)
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- 2022
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193. 20-Year Steady Increase in Survival of Adult Patients with Relapsed Philadelphia-Positive Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Cell Transplantation.
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Bazarbachi A, Labopin M, Aljurf M, Niittyvuopio R, Balsat M, Blaise D, Yakoub-Agha I, Grassi A, Reinhardt HC, Lenhoff S, Jindra P, Passweg J, Abou Dalle I, Stadler M, Lioure B, Ceballos P, Brissot E, Giebel S, Nagler A, Schmid C, and Mohty M
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- Acute Disease, Adult, Humans, Recurrence, Retrospective Studies, Transplantation Conditioning methods, Hematopoietic Stem Cell Transplantation methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Purpose: Relapse after allogeneic hematopoietic cell transplantation (allo-HCT) remains the first cause of transplant failure in patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). In other hematologic malignancies, therapeutic advances resulted in significant improvement over time in survival of patients relapsing after transplant., Experimental Design: We compared outcomes at European Society for Blood and Marrow Transplantation (EBMT) participating centers of 899 adult patients with Ph+ ALL who relapsed between 2000 and 2019 after allo-HCT performed in first complete remission. Median follow-up for alive patients was 56 months., Results: Overall, 116 patients relapsed between 2000 and 2004, 225 between 2005 and 2009, 294 between 2010 and 2014, and 264 between 2015 and 2019. Patient and transplant characteristics were similar over the four time periods except for a progressive increase in unrelated donors, peripheral blood stem cells, reduced intensity conditioning, and in vivo T-cell depletion and a progressive decrease in total body irradiation. The 2-year overall survival (OS) after relapse increased from 27.8% for patients relapsing between 2000 and 2004 to 54.8% for 2015 and 2019 (P = 0.001). A second allo-HCT within 2 years after relapse was performed in 13.9% of patients resulting in a 2-year OS of 35.9%. In multivariate analysis, OS from relapse was positively affected by a longer time from transplant to relapse and the year of relapse., Conclusions: We observed a major progressive improvement in OS from posttransplant relapse for patients with Ph+ ALL over the years, likely multifactorial including transplant-related factors, posttransplant salvage, and improvement in supportive care. These large-scale real-world data can serve as a benchmark for future studies in this setting. See related commentary by Gale, p. 813., (©2022 American Association for Cancer Research.)
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- 2022
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194. Correction: Idelalisib exposure before allogeneic stem cell transplantation in patients with follicular lymphoma: an EBMT survey.
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Sellner L, Schetelig J, Koster L, Choi G, Blaise D, Beelen D, Schianca FC, Passweg J, Schanz U, Gyan E, Sora F, Kröger N, Wulf GG, Van Gorkom G, Mayer J, Orvain C, Bourhis JH, Jindra P, Potter V, Zallio F, Vandenberghe E, Robinson S, Hayden PJ, Yakoub-Agha I, Montoto S, and Dreger P
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- 2021
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195. Natural killer cell alloreactivity in HLA-haploidentical hematopoietic transplantation: a study on behalf of the CTIWP of the EBMT.
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Ruggeri L, Vago L, Eikema DJ, de Wreede LC, Ciceri F, Diaz MA, Locatelli F, Jindra P, Milone G, Diez-Martin JL, Pérez-Simón JA, Merluzzi M, Koster L, van der Werf S, van Biezen A, Toubert A, Nagler A, Chabannon C, Bonini C, and Velardi A
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- Animals, Humans, Killer Cells, Natural, Mice, Prospective Studies, Transplantation, Haploidentical, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Abstract
Human leukocyte antigen (HLA) class-I mismatches that trigger donor-versus-recipient natural killer (NK)-cell alloreactivity reduce the incidence of leukemia relapse and improve survival of acute myeloid leukemia patients after T-cell-depleted HLA-haplotype mismatched ("haploidentical") hematopoietic transplantation. In murine graft-versus-host disease (GvHD) models, alloreactive NK-cells also prevent GvHD. Here we report the results of a non-interventional, prospective study performed on behalf of the Cellular Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation. The study was aimed at re-assessing the role of NK-cell alloreactivity in a cohort of haploidentical transplants performed in Europe between 2012 and 2015 and composed of unmanipulated, as well as T-cell-depleted transplants. One hundred thirty-eight patients with acute myeloid or lymphoid leukemias were analyzed. Eighty-six patients received ex-vivo T-cell-depleted transplants, 52 patients received unmanipulated transplants. Fifty patients were transplanted from NK alloreactive donors, 88 from non-NK alloreactive donors. NK cell alloreactivity did not impact on GvHD/relapse-free survival (GRFS) in unmanipulated transplants (HR: 1.66 (0.9-3.1), p = 0.1). In contrast, it did impact beneficially on GRFS in T-cell-depleted transplants (HR: 0.6, (0.3-1.2), p = 0.14, interaction p < 0.001). This effect was the consequence of reduced incidences of acute and chronic GvHD and non-relapse mortality., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2021
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196. Second- and third-generation tyrosine kinase inhibitors for Philadelphia-positive adult acute lymphoblastic leukemia relapsing post allogeneic stem cell transplantation-a registry study on behalf of the EBMT Acute Leukemia Working Party.
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Hirschbühl K, Labopin M, Houhou M, Gabellier L, Labussière-Wallet H, Lioure B, Beelen D, Cornelissen J, Wulf G, Jindra P, Tilly H, Passweg J, Niittyvuopio R, Bug G, Schmid C, Nagler A, Giebel S, and Mohty M
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- Adult, Humans, Philadelphia Chromosome, Protein Kinase Inhibitors therapeutic use, Recurrence, Registries, Hematopoietic Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Second- and third-generation tyrosine kinase inhibitors (TKI) play an important role in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, data on feasibility and efficacy of using these drugs for persisting or relapsed Ph + ALL after allogeneic stem cell transplantation (alloSCT) are scarce. Based on the EBMT Acute Leukemia Working Party registry, we evaluated the use of second-/third-generation TKI in 140 patients with Ph + ALL, suffering from measurable residual disease (MRD, n = 6), molecular relapse (MRel, n = 23), or hematological relapse (HRel, n = 111) following alloSCT. Treatment included dasatinib in 104, nilotinib in 18, or ponatinib in 18 patients. Forty-nine patients received TKI monotherapy, while 91 received additional treatment. Toxicity of second-/third-generation TKI post alloSCT was comparable to pretransplant use and could be managed with dose reduction or temporary discontinuation. Response rates were 71% (overall) and 61% (following TKI monotherapy). For the entire cohort, 2- and 5-year overall survival (OS) was 49% and 33%, respectively. OS was comparable among patients treated for persisting MRD/MRel and HRel. Among patients treated with TKI monotherapy, 2- and 5-year OS was 38% and 33%, respectively. The data underscore that second-/third-generation TKI are important compounds for the management of active Ph + ALL post alloSCT.
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- 2021
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197. Underdiagnosed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) as a major cause of multi-organ failure in acute leukemia transplant patients: an analysis from the EBMT Acute Leukemia Working Party.
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Bazarbachi AH, Al Hamed R, Labopin M, Halaburda K, Labussiere H, Bernasconi P, Schroyens W, Gandemer V, Schaap NPM, Loschi M, Jindra P, Snowden J, Wu D, Guffroy B, Rovira M, Chantepie SP, Poiré X, Lopez-Corral L, Nikolousis M, Pelosini M, Ciceri F, Baron F, Bazarbachi A, Corbacioglu S, Savani BN, Peric Z, Nagler A, Carreras E, and Mohty M
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- Humans, Hematopoietic Stem Cell Transplantation adverse effects, Hepatic Veno-Occlusive Disease etiology, Leukemia, Myeloid, Acute, Transplants
- Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) is a complex, potentially fatal therapy featuring a myriad of complications. Triggering event(s) of such complications vary significantly, but often a so-called "multi-organ failure" (MOF) is reported as the leading cause of death. The identification of the exact trigger of MOF is critical towards early and disease-specific intervention to improve outcome. We examined data from 202 alloHCT patients reported to have died of MOF from the EBMT registry aiming to determine their exact cause of death focusing on veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) due to its life-threatening, often difficult to capture yet preventable nature. We identified a total of 70 patients (35%) for whom VOD/SOS could be considered as trigger for MOF and leading cause of death, among which 48 (69%) were previously undiagnosed. Multivariate analysis highlighted history of hepatic comorbidity or gentuzumab use and disease status beyond CR1 as the only significant factors predictive of VOD/SOS incidence (OR = 6.6; p = 0.001 and OR = 3.3; p = 0.004 respectively). VOD/SOS-related MOF was widely under-reported, accounting for 27% of deaths attributed to MOF of unknown origin without a previous VOD/SOS diagnosis. Our results suggest most missed cases developed late VOD/SOS beyond 21 days post-alloHCT, highlighting the importance of the newly revised EBMT criteria.
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- 2021
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198. Incidence and outcome of Kaposi sarcoma after hematopoietic stem cell transplantation: a retrospective analysis and a review of the literature, on behalf of infectious diseases working party of EBMT.
- Author
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Cesaro S, Tridello G, van der Werf S, Bader P, Sociè G, Ljungman P, McQuaker G, Giardino S, Uckan-Cetinkaya D, Anagnostopoulos A, Ozdogu H, Schots R, Jindra P, Ladetto M, Schroyens W, Mikulska M, and Styczynski J
- Subjects
- Female, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Communicable Diseases, Hematopoietic Stem Cell Transplantation adverse effects, Sarcoma, Kaposi
- Abstract
The incidence, the clinical characteristics, and the outcome of Kaposi sarcoma (KS) in patients after hematopoietic stem cell transplantation (HSCT) were assessed. During the period 1987-2018, 13 cases of KS were diagnosed, 3 females and 10 males, median age of 50 years, median time from HSCT of 7 months. KS had an incidence of 0.17% in allogeneic and 0.05% in autologous HSCT. HHV-8 was documented in eight of nine tumor tissue samples assessed. The organ involvement was: skin in nine, lymph nodes in six, oral cavity in four, and visceral in three patients, respectively; seven patients had >1 organ involved. Five patients had immunosuppression withdrawn, whereas four and three patients received radiotherapy and chemotherapy, respectively. Eight patients are alive (median follow-up 48 months, range 5-128), whereas five patients died after a median time of 8 months from the diagnosis of KS. However, no death was caused by KS. We conclude that the incidence of KS after HSCT is very low. Although KS can be managed with the reduction of immunosuppression, visceral forms may require chemotherapy and/or radiotherapy. The low prevalence of KS indicates that screening for HHV-8 serology and surveillance for HHV-8 viremia are not indicated in HSCT patients.
- Published
- 2020
- Full Text
- View/download PDF
199. Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT.
- Author
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Shem-Tov N, Peczynski C, Labopin M, Itälä-Remes M, Blaise D, Labussière-Wallet H, Socié G, Kröger N, Mielke S, Afanasyev B, Chevallier P, Tischer J, Helbig G, Jindra P, Peric Z, Giebel S, Mohty M, and Nagler A
- Subjects
- Adult, Disease-Free Survival, Female, Graft vs Host Disease epidemiology, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Retrospective Studies, Transplantation, Haploidentical methods, Transplantation, Homologous methods, Treatment Outcome, Unrelated Donors, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation, Haploidentical adverse effects, Transplantation, Homologous adverse effects
- Abstract
Unmanipulated haploidentical allogeneic stem cell transplantation (Allo-SCT) has become an attractive alternative for patients lacking HLA-matched sibling or unrelated donors. However, data of outcome in ALL is still scarce. The outcomes of 1234 adult patients with ALL in first complete remission (CR1) who underwent Allo-SCT between 2007 and 2016 were analyzed. Comparison was done between haploidentical donor (Haplo) (136 patients), matched unrelated donor (MUD 10/10) (809 patients), and mismatched unrelated donor (MMUD 9/10) (289 patients). Univariate analysis showed similar outcomes in Haplo, MUD, and MMUD, including OS, LFS, RI, NRM, AGVHD, and CGVHD. In multivariate analysis, Haplo was not associated with worse outcomes compared to MUD 10/10 and MMUD 9/10. Indeed, compared to Haplo, the hazard ratio (HR) for LFS, OS, RI, NRM, AGVHD, and CGVHD were 1.1 (p = 0.7), 0.9 (p = 0.4), 1.35 (p = 0.2), 0.7 (p = 0.2), 1.1 (p = 0.8), and 0.8 (p = 0.2) for MUD, respectively, and 1.1 (p = 0.8), 1.0 (p = 1.0), 1.2 (p = 0.3), 0.8 (p = 0.4), 1.2 (p = 0.3), and 0.9 (p = 0.6) for MMUD, respectively. In conclusion, outcomes of adult patients with ALL in CR1 receiving Haplo Allo-SCT are comparable to MUD or MMUD transplants. Haplo should be considered as a clinically relevant option for patients lacking a matched sibling donor.
- Published
- 2020
- Full Text
- View/download PDF
200. Mummified Cells are a Common Finding in Cutaneous Hodgkin Lymphoma and Can Be Used as a Diagnostic Clue.
- Author
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Kastnerova L, Belousova IE, Hadravsky L, Kerl H, Cerroni L, Kerl K, Boudova L, Jindra P, Cerna K, Michal M, and Kazakov DV
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Young Adult, Hodgkin Disease pathology, Skin Neoplasms pathology
- Abstract
Specific cutaneous involvement in Hodgkin lymphoma is rare. In cutaneous lesions, the diagnosis is usually based on the recognition of diagnostic Reed-Sternberg cells and its variants. In nodal Hodgkin lymphoma, so-called mummified cells (cells with condensed cytoplasm and pyknotic eosinophilic or basophilic nuclei) are often seen. They are sometimes conspicuous and easy to recognize, thus serving as a clue to the diagnosis. Our objective was to study cases of cutaneous Hodgkin lymphoma to identify the occurrence of mummified cells. We studied 12 patients (4 women and 8 men; age range 23-80 years). In 6 patients, cutaneous and extracutaneous disease was identified almost simultaneously; in 4 patients, lymph node disease preceded cutaneous involvement; and in the remaining 2 patients, the skin lesions were the presenting sign, whereas lymph node involvement occurred later. Histopathological, immunohistochemical, and molecular-genetic studies, including rearrangements for TCR, IgH genes, and PCR for EBV, were performed. Cutaneous biopsy specimens revealed either a multinodular or diffuse infiltrate, included small lymphocytes, eosinophils, plasma cells, and macrophages, but in all cases, diagnostic Reed-Sternberg cells and its variants were identified. Mummified cells were detected in 9 cases, either as occasional scattered mummified cells often requiring a search (6 cases) or being conspicuous, grouped and therefore easily identified (3 cases). Immunohistochemically, in all 7 cases studied, mummified cells were positive for both CD30 and CD15. It is concluded that mummified cells are encountered in a majority of cases of cutaneous Hodgkin lymphoma.
- Published
- 2020
- Full Text
- View/download PDF
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