31 results on '"Koster L"'
Search Results
2. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors
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Styczynski, J., Tridello, G., Koster, L., Iacobelli, S., Biezen, A. van, Werf, S. van der, Mikulska, M., Gil, L., Cordonnier, C., Ljungman, P., Averbuch, D., Cesaro, S., Camara, R. de la, Baldomero, H., Bader, P., Basak, G., Bonini, C., Duarte, R., Dufour, C., Kuball, J., Lankester, A., Montoto, S., Nagler, A., Snowden, J.A., Kroger, N., Mohty, M., Gratwohl, A., Infect Dis Working Party EBMT, UAM. Departamento de Medicina, Styczynski, J., Tridello, G., Koster, L., Iacobelli, S., van Biezen, A., van der Werf, S., Mikulska, M., Gil, L., Cordonnier, C., Ljungman, P., Averbuch, D., Cesaro, S., de la Camara, R., Baldomero, H., Bader, P., Basak, G., Bonini, C., Duarte, R., Dufour, C., Kuball, J., Lankester, A., Montoto, S., Nagler, A., Snowden, J. A., Kroger, N., Mohty, M., and Gratwohl, A.
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medicine.medical_specialty ,Medicina ,Epidemiology ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Disease ,Infections ,survival ,Communicable Diseases ,Article ,Cohort Studies ,cause of death ,Internal medicine ,stem cell transplant ,medicine ,Humans ,Haematopoietic stem cell transplantation (HSCT) ,Risk factor ,Cause of death ,Transplantation ,Leukemia ,stem cell transplant, cause of death, survival ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Hematology ,Settore MED/15 ,Death ,Settore MED/01 ,surgical procedures, operative ,Risk factors ,Mycoses ,Cohort ,business ,Cohort study - Abstract
Information on incidence, and factors associated with mortality is a prerequisite to improve outcome after hematopoietic stem cell transplantation (HSCT). Therefore, 55′668 deaths in 114′491 patients with HSCT (83.7% allogeneic) for leukemia were investigated in a landmark analysis for causes of death at day 30 (very early), day 100 (early), at 1 year (intermediate) and at 5 years (late). Mortality from all causes decreased from cohort 1 (1980–2001) to cohort 2 (2002–2015) in all post-transplant phases after autologous HSCT. After allogeneic HSCT, mortality from infections, GVHD, and toxicity decreased up to 1 year, increased at 5 years; deaths from relapse increased in all post-transplant phases. Infections of unknown origin were the main cause of infectious deaths. Lethal bacterial and fungal infections decreased from cohort 1 to cohort 2, not unknown or mixed infections. Infectious deaths were associated with patient-, disease-, donor type, stem cell source, center, and country- related factors. Their impact varied over the post-transplant phases. Transplant centres have successfully managed to reduce death after HSCT in the early and intermediate post-transplant phases, and have identified risk factors. Late post-transplant care could be improved by focus on groups at risk and better identification of infections of “unknown origin”., The study was funded by the European Group for Blood and Marrow Transplantation EBMT
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- 2019
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3. Trends in allogeneic haematopoietic cell transplantation for myelofibrosis in Europe between 1995 and 2018: a CMWP of EBMT retrospective analysis
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McLornan, D., primary, Eikema, D. J., additional, Czerw, T., additional, Kröger, N., additional, Koster, L., additional, Reinhardt, Hans Christian, additional, Angelucci, E., additional, Robin, M., additional, Bornhäuser, M., additional, Passweg, J., additional, Clark, A., additional, Vydra, J., additional, Blau, I. E., additional, Niittyvuopio, R., additional, Platzbecker, U., additional, Cornelissen, J. J., additional, Chevallier, P., additional, Srour, M., additional, Stamatovic, D., additional, Martinez-Lopez, J., additional, de Wreede, L., additional, Hayden, P., additional, Hernández-Boluda, J. C., additional, and Yakoub-Agha, I., additional
- Published
- 2021
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4. Satisfactory outcomes following a second autologous hematopoietic cell transplantation for multiple myeloma in poor stem cell mobilizers: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.
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Sever M, Drozd-Sokolowska J, Gras L, Koster L, Folber F, Mielke S, Fenk R, Basak G, Apperley J, Byrne J, Rambaldi A, Ringhoffer M, Eder M, Trneny M, Blaise D, Lenhoff S, Isaksson C, Passweg J, Partanen A, Sakellari I, Schönland S, Morris C, Beksac M, Raj K, Hayden PJ, and McLornan DP
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- Humans, Male, Female, Middle Aged, Retrospective Studies, Adult, Aged, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy, Multiple Myeloma mortality, Hematopoietic Stem Cell Mobilization methods, Transplantation, Autologous methods
- Abstract
Autologous hematopoietic cell transplants (auto-HCTs) remain the standard of care for transplant-eligible MM patients. The general practice has been to undergo upfront apheresis following induction to collect sufficient number of CD34+ cells to facilitate two auto-HCTs. However, 5-30% of MM patients do not initially mobilise a sufficient number of hematopoietic stem cells and are classified as poor mobilizers (PM). We compared the baseline characteristics and outcomes of 61 PMs and 816 non-PM patients who underwent a second auto-HCT and who were enrolled in the non-interventional CALM study (NCT01362972). Only patients who collected CD34+ prior to auto-HCT1 were included. Auto-HCT2 comprised both tandem and salvage transplants. PMs were re-mobilized with plerixafor (n = 24, 39.3%) or non-plerixafor-based regimens (n = 37, 60.7%). There were no significant differences in engraftment, progression-free survival (PFS) or overall survival (OS) after the second auto-HCT between PM and non-PM patients. There was a trend to shorter PFS in PM patients undergoing salvage auto-HCT (median 9.6 vs. 12.9 months; p = 0.08) but no significant difference in OS. The median OS was 41.1 months for PM and 41.2 months for non-PM patients (p = 0.86). These data suggest that salvage mobilization is effective and does not affect overall outcomes after a second auto-HCT., Competing Interests: Competing interests: JDS – honoraria AbbVie, Roche, Janssen, Astra Zeneca, SOBI, Takeda, BMS, Novartis, Swixx; Advisory board meetings organized by Janssen-Cilag, Sanofi, AstraZeneca, Roche, BeiGene; AP - honoraria from Behring and Abbvie, participation in scientific Advisory board meetings organized by Abbvie, Janssen-Cilag, Novartis, Pfizer, Sanofi and Takeda; none of COI directly related to the study. Ethics approval: This retrospective study was approved by the Chronic Malignancies Working Party (CMWP) of the EBMT and was performed in accordance with the Declaration of Helsinki., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2025
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5. Allogeneic hematopoietic cell transplantation for therapy-related myeloid neoplasms arising following treatment for multiple myeloma: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.
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Raj K, Eikema DJ, Lawless S, Koster L, Kunadt D, Kröger N, Platzbecker U, Stelljes M, Bethge W, Holderried T, Fanin R, Zeiser R, Kuball J, Leblond V, Nicholson E, Passweg J, Potter V, Bay JO, Bazarbachi A, Corral LL, Gurnari C, Scheid C, Drozd-Sokolowska J, Morris TC, Hayden P, Yakoub-Agha I, Robin M, and McLornan DP
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- Humans, Retrospective Studies, Middle Aged, Male, Female, Aged, Adult, Neoplasms, Second Primary etiology, Neoplasms, Second Primary therapy, Transplantation, Homologous methods, Registries, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation adverse effects, Multiple Myeloma therapy, Multiple Myeloma mortality
- Abstract
Therapy-related myeloid neoplasms (t-MN) are a complication of multiple myeloma (MM) treatment. Our retrospective, EBMT registry study included 157 such patients allografted (allo-HCT) between 2006 and 2018. Most patients (130) had a prior autologous HCT. Fifty-seven (36.4%) were transplanted for t-AML and 100 (63.6%) for t-MDS. Median times from MM and t-MN diagnoses to allo-HCT were 72.6 (interquartile range (IQR), 46.1-102.9) and 6.4 (IQR, 3.9-9.4) months. Fifty-eight (38.4%) t-MN patients were in complete remission (CR) at allo-HCT predominantly conditioned with reduced intensity (70.3%). With a median follow-up of 64.9 (95% CI: 39-76) months, relapse incidence (RI) from MM at 1 and 5 years was 4% (0-10%) and 12% (2-22%), respectively, with few deaths (n = 3) only due to MM disease progression, whereas t-MN RI and non-relapse mortality (NRM) at 1 and 5 years were 35% (95% CI 28-43%) and 45% (95% CI: 36-53%) and 20% (95% CI 13-26%) and 31% (95% CI: 23-39%). Overall survival (OS) and progression-free survival (PFS) estimates at 1 and 5 years were 55% (95% CI: 47-63%) and 27% (95% CI: 19-35%) and 45% (95% CI 36-53%) and 24% (95% CI 16-32%). Older (>65 years) t-MN patients with high-risk cytogenetics do not benefit from allo-HCT., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2025
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6. Reduced intensity versus myeloablative conditioning for MDS: long-term results of an EBMT phase III study (RICMAC).
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Niederwieser C, Iacobelli S, Franke GN, Koster L, van Os M, Platzbecker U, Hübel K, Scheid C, Müller LP, Stelljes M, Morozova E, Passweg J, Onida F, Dreger P, Saccardi R, Ladetto M, Salmenniemi U, Bethge W, Poiré X, Kobbe G, McLornan DP, Robin M, and Kröger N
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- Humans, Middle Aged, Adult, Male, Female, Aged, Busulfan therapeutic use, Busulfan administration & dosage, Hematopoietic Stem Cell Transplantation methods, Adolescent, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Vidarabine administration & dosage, Cyclophosphamide therapeutic use, Myeloablative Agonists therapeutic use, Young Adult, Follow-Up Studies, Prospective Studies, Transplantation Conditioning methods, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes mortality
- Abstract
Short-term outcome of myeloablative (MAC) and reduced intensity (RIC) conditioning in the prospective randomized international EBMT RICMAC study in patients with myelodyplastic syndrome (MDS) was comparable but longer follow up is lacking. Patients with MDS aged 18-65 years were randomized to receive MAC (N = 64) with busulfan/cyclophosphamide or RIC (n = 65) with busulfan/fludarabine followed by stem cell transplantation -(HCT) from HLA matched or mismatched donor. After a median follow-up of 6.2 (0.4-12.5) years, 10-year OS and RFS were 54.0% and 43.9% for RIC and 44.4% and 44.2% for MAC (p = 0.15 and p = 0.78), respectively. Since the first report, 6 patients died on NRM, 4 after RIC, and 2 after MAC. Similarly, 8 patients relapsed (4 in each arm), increasing the number of relapsed patients to 28. The second HCT was performed in 18 pts, 8 in the MAC, and 10 in the RIC arm. In a multivariate analysis, ECOG status and chemotherapy prior to HCT were independent risk factors for OS and RFS, ECOG and low cytogenetic risk for NRM and chemotherapy prior to HCT for RI. Patients with low cytogenetic risk had better OS [p = 0.002], RFS [p = 0.02], and NRM (p = 0.015) after RIC as compared to MAC., (© 2024. The Author(s).)
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- 2024
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7. Correction: Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: a registry-based study from the Chronic Malignancies Working Party of the EBMT.
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Robin M, Iacobelli S, Koster L, Passweg J, Avenoso D, Wilson KMO, Salmenniemi U, Dreger P, von dem Borne P, Snowden JA, Robinson S, Finazzi MC, Schroeder T, Collin M, Eder M, Forcade E, Loschi M, Bramanti S, Pérez-Simón JA, Czerw T, Polverelli N, Drozd-Sokolowska J, Raj K, Hernández-Boluda JC, and McLornan DP
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- 2024
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8. Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: a registry-based study from the Chronic Malignancies Working Party of the EBMT.
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Robin M, Iacobelli S, Koster L, Passweg J, Avenoso D, Wilson KMO, Salmenniemi U, Dreger P, von dem Borne P, Snowden JA, Robinson S, Finazzi MC, Schroeder T, Collin M, Eder M, Forcade E, Loschi M, Bramanti S, Pérez-Simón JA, Czerw T, Polverelli N, Drozd-Sokolowska J, Raj K, Hernández-Boluda JC, and McLornan DP
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- Humans, Middle Aged, Male, Female, Adult, Aged, Transplantation Conditioning methods, Transplantation, Homologous methods, Graft vs Host Disease mortality, Busulfan analogs & derivatives, Busulfan therapeutic use, Primary Myelofibrosis therapy, Primary Myelofibrosis mortality, Hematopoietic Stem Cell Transplantation methods, Registries
- Abstract
We aimed to compare outcomes following treosulfan (TREO) or busulfan (BU) conditioning in a large cohort of myelofibrosis (MF) patients from the EBMT registry. A total of 530 patients were included; 73 received TREO and 457 BU (BU ≤ 6.4 mg/kg in 134, considered RIC, BU > 6.4 mg/kg in 323 considered higher dose (HD)). Groups were compared using adjusted Cox models. Cumulative incidences of engraftment and acute GVHD were similar across the 3 groups. The TREO group had significantly better OS than BU-HD (HR:0.61, 95% CI: 0.39-0.93) and a trend towards better OS over BU-RIC (HR: 0.66, 95% CI: 0.41-1.05). Moreover, the TREO cohort had a significantly better Progression-Free-Survival (PFS) than both the BU-HD (HR: 0.57, 95% CI: 0.38-0.84) and BU-RIC (HR: 0.60, 95% CI: 0.39-0.91) cohorts, which had similar PFS estimates. Non-relapse mortality (NRM) was reduced in the TREO and BU-RIC cohorts (HR: 0.44, 95% CI: 0.24-0.80 TREO vs BU-HD; HR: 0.54, 95% CI: 0.28-1.04 TREO vs BU-RIC). Of note, relapse risk did not significantly differ across the three groups. In summary, within the limits of a registry-based study, TREO conditioning may improve PFS in MF HSCT and have lower NRM than BU-HD with a similar relapse risk to BU-RIC. Prospective studies are needed to confirm these findings., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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9. Allogeneic hematopoietic stem-cell transplantation for patients with Richter transformation: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.
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Guièze R, Eikema DJ, Koster L, Schetelig J, Sengeloev H, Passweg J, Finke J, Arat M, Broers AEC, Stölzel F, Byrne J, Castilla-Llorente C, Dreger P, Eder M, Gedde-Dahl T, Kröger N, Ribera Santasusana JM, Richardson D, Rambaldi A, Yañez L, Van Gelder M, Drozd-Sokolowska J, Raj K, Yakoub-Agha I, Tournilhac O, and McLornan DP
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- Humans, Middle Aged, Retrospective Studies, Male, Female, Transplantation, Homologous methods, Transplantation Conditioning methods, Graft vs Host Disease mortality, Adult, Allografts, Hematopoietic Stem Cell Transplantation methods
- Abstract
Management of Richter transformation (RT) is particularly challenging, with survival estimates <1 year. We report on outcomes of 66 RT patients undergoing allogeneic-HCT (allo-HCT) between 2008 and 2018 registered with the EBMT. Median age at allo-HCT was 56.2 years (interquartile range (IQR), 51.3-63.1). Median time from RT to allo-HCT was 6.9 months (IQR, 4.9-11) and 28 (42.4%) were in complete remission (CR). The majority underwent reduced intensity conditioning (66.2%) using peripheral blood derived stem cells. Eighteen (27.3%) patients had a matched sibling donor, 24 (36.4%) a matched unrelated donor and the remaining were mismatched. Median follow-up was 6.6 years; 1- and 3- year overall and progression free survival (PFS) (95% CI) was 65% (54-77) and 39% (27-51) and 53% (41-65) and 29% (18-40), respectively. Patients in CR at time of allo-HCT had significantly better 3-year PFS (39% vs. 21%, p = 0.032). Cumulative incidences of grade II-IV acute graft versus host disease (GVHD) at day +100 was 41% (95% CI 29-53) and chronic GVHD at 3 years was 53% (95% CI 41-65). High rates of non-relapse mortality (NRM) were observed; 38% (95% CI, 26-50) at 3 years. Although potentially curative, approaches to reduce considerable NRM and chronic GVHD rates are required., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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10. Fludarabine-treosulfan versus fludarabine-melphalan or busulfan-cyclophosphamide conditioning in older AML or MDS patients - A clinical trial to registry data comparison.
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Beelen DW, Iacobelli S, Koster L, Eikema DJ, van Biezen A, Stölzel F, Ciceri F, Bethge W, Dreger P, Wagner-Drouet EM, Reményi P, Stelljes M, Markiewicz M, McLornan DP, Yakoub-Agha I, and Mohty M
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- Humans, Aged, Middle Aged, Female, Male, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Hematopoietic Stem Cell Transplantation methods, Busulfan analogs & derivatives, Busulfan therapeutic use, Busulfan administration & dosage, Busulfan pharmacology, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Vidarabine pharmacology, Vidarabine administration & dosage, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute mortality, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes drug therapy, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Cyclophosphamide pharmacology, Transplantation Conditioning methods, Registries, Melphalan therapeutic use, Melphalan administration & dosage, Melphalan pharmacology
- Abstract
A randomized study (acronym: MC-FludT.14/L Trial II) demonstrated that fludarabine plus treosulfan (30 g/m²) was an effective and well tolerated conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To further evaluate this regimen, all 252 study patients aged 50 to 70 years were compared with similar patients, who underwent allo-HCT after fludarabine/melphalan (140 mg/m²) (FluMel) or busulfan (12.8 mg/kg)/cyclophosphamide (120 mg/kg) (BuCy) regimens and whose data was provided by the European Society for Blood and Marrow Transplantation registry. In 1:1 propensity-score matched-paired analysis (PSA) of AML patients, there was no difference in 2-year-relapse-incidence after FluTreo compared with either FluMel (n = 110, p = 0.28) or BuCy (n = 78, p = 0.98). However, 2-year-non-relapse-mortality (NRM) was lower compared with FluMel (p = 0.019) and BuCy (p < 0.001). Consequently, 2-year-overall-survival (OS) after FluTreo was higher compared with FluMel (p = 0.04) and BuCy (p < 0.001). For MDS patients, no endpoint differences between FluTreo and FluMel (n = 30) were evident, whereas 2-year-OS after FluTreo was higher compared with BuCy (n = 25, p = 0.01) due to lower 2-year-NRM. Multivariate sensitivity analysis confirmed all significant results of PSA. Consequently, FluTreo (30 g/m²) seems to retain efficacy compared with FluMel and BuCy, but is better tolerated by older patients., (© 2024. The Author(s).)
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- 2024
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11. Impact of post-transplant cyclophosphamide (PTCy)-based prophylaxis in matched sibling donor allogeneic haematopoietic cell transplantation for patients with myelodysplastic syndrome: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.
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Salas MQ, Eikema DJ, Koster L, Maertens J, Passweg J, Finke J, Broers AEC, Koc Y, Kröger N, Ozkurt ZN, Pascual-Cascon MJ, Platzbecker U, Van Gorkom G, Schroeder T, López-Lorenzo JL, Martino M, Chiusolo P, Kaufmann M, Onida F, Gurnari C, Scheid C, Drozd-Sokolowska J, Raj K, Robin M, and McLornan DP
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- Humans, Retrospective Studies, Siblings, Cyclophosphamide therapeutic use, Cyclophosphamide pharmacology, Unrelated Donors, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Myelodysplastic Syndromes complications, Neoplasms complications
- Abstract
We retrospectively compared outcomes of 404 MDS patients undergoing 1st matched sibling donor allo-HCT receiving either PTCy-based (n = 66) or other "conventional prophylaxis" (n = 338; mostly calcineurin inhibitor + methotrexate or MMF). Baseline characteristics were balanced, except for higher use of myeloablative regimens in the PTCy group (52.3% vs. 38.2%, p = 0.047). Incidences of neutrophil (Day +28: 89% vs. 97%, p = 0.011) and platelet (Day +100: 89% vs. 97%, p < 0.001) engraftment were lower for PTCy-based. Day +100 cumulative incidences of grade II-IV and III-IV aGVHD, and 5-year CI of extensive cGVHD were 32%, 18% and 18% for PTCy-based and 25% (p = 0.3), 13% (p = 0.4) and 31% (p = 0.09) for the conventional cohort. Five-year OS (51% vs. 52%, p = 0.6) and GRFS (33% vs. 25%, p = 0.6) were similar between groups. Patients receiving PTCy had a trend to a lower cumulative incidence of relapse (20% vs. 33%, p = 0.06), not confirmed on multivariable analysis (p = 0.3). Although higher NRM rates were observed in patients receiving PTCy (32% vs. 21%, p = 0.02) on univariate analysis, this was not confirmed on multivariate analysis (HR 1.46, p = 0.18), and there was no resultant effect on OS (HR 1.20, p = 0.5). Based on these data, PTCy prophylaxis appears to be an attractive option for patients with MDS undergoing MSD allo-HCT., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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12. In the era of Bortezomib-based Induction, intensification of Melphalan-based conditioning with Bortezomib does not improve Survival Outcomes in newly diagnosed Multiple Myeloma: a study from the Chronic Malignancies Working Party of the EBMT.
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Beksac M, Eikema DJ, Koster L, Hulin C, Poiré X, Hamladji RM, Gromek T, Bazarbachi A, Ozkurt ZN, Pabst T, Ben Othman T, Finke J, Pirogova O, Wu D, Hayat A, Hilgendorf I, Tholouli E, de Wreede LC, Schönland S, Garderet L, Drozd-Sokolowska J, Raj K, Hayden PJ, Yakoub-Agha I, and McLornan DP
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- Humans, Bortezomib pharmacology, Bortezomib therapeutic use, Melphalan pharmacology, Melphalan therapeutic use, Prospective Studies, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols, Multiple Myeloma drug therapy, Multiple Myeloma diagnosis, Hematopoietic Stem Cell Transplantation
- Abstract
Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres. Pre-AHCT, compared to Mel200 patients, Vel-Mel patients had similar International Staging System (ISS) scores and cytogenetic risk profiles; a similar proportion had received bortezomib-based induction (85% and 87.3%, respectively) though they were younger with a better performance status. Vel-Mel patients were more likely to achieve CR post-induction (40.6% vs 20.3%, p < 0.001) and by day 100 of AHCT (CR/VGPR: 70.2 % vs. 57.2%, p < 0.001). There was no difference in 3-year PFS (49% vs 46%, p = 0.06) or early post-AHCT mortality. In multivariable analysis, Vel-Mel associated with inferior PFS (HR: 1.69 (1.27-2.25, p < 0.001) and OS (HR:1.46 (1.14-1.86,p = 0.002), similar to negative effects on PFS of advanced ISS (HR:1.56 (1.33-1.83, p < 0.001), high-risk cytogenetics (HR:1.43(1.18-1.74, p < 0.001) and poor post-induction response(<=PR)(HR: 1.43(1.25-1.62, p < 0.001) Overall, despite superior pre- and post-AHCT responses, there was no improvement in PFS or OS following Vel-Mel. This data supports the findings of the smaller prospective IFM study., (© 2024. The Author(s).)
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- 2024
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13. Allogeneic haematopoietic cell transplantation for therapy-related myeloid neoplasms arising following treatment for lymphoma: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.
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Nabergoj M, Eikema DJ, Koster L, Platzbecker U, Sockel K, Finke J, Kröger N, Forcade E, Nagler A, Eder M, Tischer J, Broers AEC, Kuball J, Wilson KMO, Hunault-Berger M, Collin M, Russo D, Corral LL, Helbig G, Mussetti A, Scheid C, Gurnari C, Raj K, Drozd-Sokolowska J, Yakoub-Agha I, Robin M, and McLornan DP
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- Humans, Middle Aged, Retrospective Studies, Recurrence, Transplantation Conditioning, Leukemia, Myeloid, Acute therapy, Lymphoma etiology, Lymphoma therapy, Neoplasms, Second Primary etiology, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology
- Abstract
Therapy-related myeloid neoplasms (t-MN), either myelodysplastic neoplasms (t-MDS) or acute myeloid leukemias (t-AML), have a poor prognosis and allogeneic haematopoietic cell transplantation (allo-HCT) represents the only curative option. In this multicenter, registry-based study, we analyzed outcomes of 378 patients undergoing first allo-HCT between 2006-2017 for t-MN arising secondary to lymphoma treatment. Median age was 58 years at allo-HCT; 222 (59%) had a diagnosis of t-MDS and 156 (41%) of t-AML, respectively. At the time of allo-HCT, 46% of t-MN cases were reported as in complete remission (CR) and 15% of lymphomas were recorded as not in remission. A reduced intensity conditioning regimen was used in 70% of cases. For the entire cohort, 5-year OS, and t-MN PFS, relapse incidence and NRM were 32%, 28%, 35% and 37%, respectively. In multivariable analysis, undergoing allo-HCT with t-MN not in CR and older age were associated with significantly worse OS, PFS and NRM. At 5 years post allo-HCT, the relapse incidence of lymphoma was low at 3%, while the rate of secondary malignancies was 8%. This analysis shows the curative potential of allo-HCT for patients with t-MN arising secondary to lymphoma treatment in approximately a third of patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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14. Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT.
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Potter V, Gras L, Koster L, Kroger N, Sockel K, Ganser A, Finke J, Labussiere-Wallet H, Peffault de Latour R, Koc Y, Salmenniemi U, Smidstrup Friis L, Jindra P, Schroeder T, Tischer J, Arat M, Pascual Cascon M, de Wreede LC, Hayden P, Raj K, Drozd-Sokolowska J, Scheid C, McLornan DP, Robin M, and Yakoub-Agha I
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- Humans, Middle Aged, Aged, Retrospective Studies, Transplantation, Homologous methods, Neoplasm Recurrence, Local, Chronic Disease, Transplantation Conditioning methods, Myelodysplastic Syndromes therapy, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease etiology
- Abstract
The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
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15. Allogeneic hematopoietic cell transplantation in patients with CALR-mutated myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT.
- Author
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Hernández-Boluda JC, Eikema DJ, Koster L, Kröger N, Robin M, de Witte M, Finke J, Finazzi MC, Broers A, Raida L, Schaap N, Chiusolo P, Verbeek M, Hazenberg CLE, Halaburda K, Kulagin A, Labussière-Wallet H, Gedde-Dahl T, Rabitsch W, Raj K, Drozd-Sokolowska J, Battipaglia G, Polverelli N, Czerw T, Yakoub-Agha I, and McLornan DP
- Subjects
- Humans, Transplantation, Homologous adverse effects, Retrospective Studies, Chronic Disease, Recurrence, Transplantation Conditioning adverse effects, Primary Myelofibrosis genetics, Primary Myelofibrosis therapy, Primary Myelofibrosis complications, Hematopoietic Stem Cell Transplantation adverse effects, Neoplasms complications, Graft vs Host Disease etiology
- Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is curative for myelofibrosis (MF) but assessing risk-benefit in individual patients is challenging. This complexity is amplified in CALR-mutated MF patients, as they live longer with conventional treatments compared to other molecular subtypes. We analyzed outcomes of 346 CALR-mutated MF patients who underwent allo-HCT in 123 EBMT centers between 2005 and 2019. After a median follow-up of 40 months, the estimated overall survival (OS) rates at 1, 3, and 5 years were 81%, 71%, and 63%, respectively. Patients receiving busulfan-containing regimens achieved a 5-year OS rate of 71%. Non-relapse mortality (NRM) at 1, 3, and 5 years was 16%, 22%, and 26%, respectively, while the incidence of relapse/progression was 11%, 15%, and 17%, respectively. Multivariate analysis showed that older age correlated with worse OS, while primary MF and HLA mismatched transplants had a near-to-significant trend to decreased OS. Comparative analysis between CALR- and JAK2-mutated MF patients adjusting for confounding factors revealed better OS, lower NRM, lower relapse, and improved graft-versus-host disease-free and relapse-free survival (GRFS) in CALR-mutated patients. These findings confirm the improved prognosis associated with CALR mutation in allo-HCT and support molecular profiling in prognostic scoring systems to predict OS after transplantation in MF., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
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16. Correction: An early post-transplant relapse prediction score in multiple myeloma: a large cohort study from the chronic malignancies working party of EBMT.
- Author
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Beksac M, Iacobelli S, Koster L, Cornelissen J, Griskevicius L, Rabin NK, Stoppa AM, Meijer E, Mear JB, Zeerleder S, Mayer J, Fenk R, Fegueux N, Chevallier P, Konirova E, Snowden JA, Engelhardt M, Orchard K, Hulin C, Schaap N, Sossa C, Elmaagacli A, McLornan DP, Hayden PJ, Schönland S, and Yakoub-Agha I
- Published
- 2023
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- View/download PDF
17. Are syngeneic donors a viable donor option in allogeneic haematopoietic cell transplantation for MDS? A brief report on behalf of the Chronic Malignancies Working Party of the EBMT and review of current literature.
- Author
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Robin M, Gras L, Koster L, Saccardi R, Finke J, Forcade E, Rovira M, Kobbe G, Reményi P, Apperley J, Smaranda A, Bay JO, Casper J, de Wreede LC, Giebel S, Grillo G, Heras I, Potter V, Tischer J, Trociukas I, Nachbaur D, Drozd-Sokolowska J, Raj K, Gurnari C, Yakoub-Agha I, Onida F, Scheid C, and McLornan D
- Subjects
- Humans, Tissue Donors, Retrospective Studies, Transplantation Conditioning, Hematopoietic Stem Cell Transplantation, Neoplasms, Graft vs Host Disease
- Published
- 2023
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18. Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT.
- Author
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Styczynski J, Tridello G, Koster L, Knelange N, Wendel L, van Biezen A, van der Werf S, Mikulska M, Gil L, Cordonnier C, Ljungman P, Averbuch D, Cesaro S, Baldomero H, Chabannon C, Corbacioglu S, Dolstra H, Glass B, Greco R, Kröger N, de Latour RP, Mohty M, Neven B, Peric Z, Snowden JA, Sureda A, Yakoub-Agha I, and de la Camara R
- Subjects
- Humans, Cause of Death, Chronic Disease, Retrospective Studies, Hematopoietic Stem Cell Transplantation methods, Communicable Diseases etiology, Lymphoma, Leukemia, Myeloid, Acute etiology
- Abstract
We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980-2001 (cohort-1) and 2002-2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
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19. An early post-transplant relapse prediction score in multiple myeloma: a large cohort study from the chronic malignancies working party of EBMT.
- Author
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Beksac M, Iacobelli S, Koster L, Cornelissen J, Griskevicius L, Rabin NK, Stoppa AM, Meijer E, Mear JB, Zeerleder S, Mayer J, Fenk R, Fegueux N, Chevallier P, Konirova E, Snowden JA, Engelhardt M, Orchard K, Hulin C, Schaap N, Sossa C, Elmaagacli A, McLornan DP, Hayden PJ, Schönland S, and Yakoub-Agha I
- Subjects
- Humans, Cohort Studies, Neoplasm Recurrence, Local, Transplantation Conditioning, Melphalan, Transplantation, Autologous, Multiple Myeloma therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Early relapse (ER) following Autologous Hematopoietic Cell Transplantation (AHCT) confers a poor prognosis. We therefore developed a novel scoring system to predict ER. A total of 14,367 AHCT-1 patients were transplanted between 2014 and 2019, and were conditioned with Melphalan 200 mg/m
2 (Mel200) (n = 7228; 2014-2017) (training cohort); Mel200 (n = 5616; 2018-2019) or Mel140 (n = 1523; 2018-2019) (validation cohorts). PFS-12 and the Cumulative Incidence of Relapse at 12 months were 84.1% and 14.7% (training Mel200), 87.2% and 11.6% (validation Mel200), and 80.3% and 16.9% (validation Mel140), respectively. The points in the risk score were: 0, 1,2 for ISS stages I, II, and III; Disease status: 0 (CR/VGPR); 1 (PR); 2 (SD/MR); 4 (Relapse/Progression); and 1 for Karnofsky ≤ 70. The distribution of scores: 0 (24%), 1 (33.9%), 2 (29.6 %), 3 (9.5%), and ≥4 (2.7%). The score separated PFS-12, with the lowest risk group (n = 1752) having a PFS-12 of 91.7% and the highest risk group (n = 195) 57.1%. This also applied in cytogenetically high-risk patients. If the pre-score baseline risks are 15% (standard risk) and 25% (high-risk), a score of ≥4 confers calculated risks of 38% and 54%, respectively. This novel EBMT ER score, therefore, allows for the identification of five discrete prognostic groups., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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20. Allogeneic hematopoietic cell transplantation in patients with therapy-related myeloid neoplasm after breast cancer: a study of the Chronic Malignancies Working Party of the EBMT.
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Nabergoj M, Mauff K, Beelen D, Ganser A, Kröger N, Stölzel F, Finke J, Passweg J, Cornelissen J, Schub N, Veelken JH, Beguin Y, Wilson K, Zuckerman T, Hunault-Berger M, Lioure B, Porras RP, Turlure P, Kerre T, Koster L, Hayden PJ, Onida F, Scheid C, Chalandon Y, Robin M, and Yakoub-Agha I
- Subjects
- Female, Humans, Middle Aged, Recurrence, Retrospective Studies, Transplantation Conditioning, Breast Neoplasms therapy, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute therapy, Myeloproliferative Disorders
- Abstract
We performed a registry study on therapy-related myeloid neoplasm (t-MN), both therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) following treatment for breast cancer who underwent a first allogeneic hematopoietic cell transplant (allo-HCT). Of 252 identified female patients (median age 57 years), 77% were transplanted for t-AML and 23% for t-MDS, with a median time from breast cancer diagnosis to the diagnosis of tMN and subsequent allo-HCT of 3.7 and 4.6 years, respectively. At transplant, 191 patients were in remission for breast cancer, while 4 were not (57 missing). T-MN was in a complete remission at the time of transplant in 67% of patients. 2-year overall survival, relapse free-survival, relapse incidence and non-relapse mortality were 50%, 45%, 33%, and 22%, respectively. Multivariable analysis revealed that if the t-MN was not in CR pre-transplant, this was associated with lower OS, RFS, and a higher relapse incidence. Seventeen cases of breast cancer recurrence were recorded after a median of 2.4 years post-transplant, and relapse of primary breast cancer accounted for 7% of deaths. This study indicates that allo-HCT for t-MN following treatment for breast cancer shows encouraging transplant outcomes. The incidence of breast cancer relapse post-transplant remains a cause for concern., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2022
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21. Prognostic value of a new clinically-based classification system in patients with CMML undergoing allogeneic HCT: a retrospective analysis of the EBMT-CMWP.
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Onida F, Sbianchi G, Radujkovic A, Sockel K, Kröger N, Sierra J, Socié G, Cornelissen J, Poiré X, Raida L, Bourhis JH, Finke J, Passweg J, Salmenniemi U, Schouten HC, Beguin Y, Martin S, Deconinck E, Ganser A, Zver S, Lioure B, Rohini R, Koster L, Hayden P, Iacobelli S, Robin M, and Yakoub-Agha I
- Subjects
- Humans, Prognosis, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Leukemia, Myelomonocytic, Chronic
- Abstract
Recently a new three-group clinical classification was reported by an International Consortium to stratify CMML patients with regard to prognosis. The groups were defined as follows: (1) Myelodysplastic (MD)-CMML: WBC ≤ 10 × 10
9 /l, circulating immature myeloid cells (IMC) = 0, no splenomegaly; (2) MD/MP (overlap)-CMML: WBC 10-20 × 109 /l or WBC ≤ 10 × 109 /l but IMC > 0 and/or splenomegaly; (3) Myeloproliferative (MP)-CMML: WBC > 20 × 109 /l. By analysing EBMT Registry patients who underwent allo-HCT for CMML between 1997 and 2016, we aimed to determine the impact of this classification on transplantation outcome and to make a comparison with the conventional WHO classification (CMML-0/CMML-1/CMML-2). Patient grouping was based on the data registered at time of transplantation, with IMC replaced by peripheral blasts. Among 151 patients included in the analysis, 38% were classified as MD-CMML, 42% as MD/MP-CMML and 20% as MP-CMML. With a median survival of 17 months in the whole series, MD-CMML patients were distinguished as a low-risk group with higher CR rate at transplant and a longer post-transplant 2-year progression-free survival in comparison to others (44.5% vs 33.5%, respectively), whereas the WHO classification was superior in identifying high-risk patients (CMML-2) with inferior survival outcomes., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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22. 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.
- Author
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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
- Subjects
- 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.)
- Published
- 2022
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23. Daratumumab after allogeneic hematopoietic cell transplantation for multiple myeloma is safe and synergies with pre-existing chronic graft versus host disease. A retrospective study from the CMWP EBMT.
- Author
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Vincent L, Gras L, Ceballos P, Finke J, Passweg J, Harel S, Rosinol L, Minnema M, Teipel R, van Doesum J, Hänel M, Lenain P, Botella-Garcia C, Koenecke C, Ducastelle S, Sanz J, Schroyens W, Zuckerman T, Monaco F, Koster L, de Wreede L, Hayden PJ, Schönland S, Yakoub-Agha I, and Beksac M
- Subjects
- Antibodies, Monoclonal, Humans, Retrospective Studies, Transplantation Conditioning, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy
- Published
- 2022
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- View/download PDF
24. Impact of donor-derived CD34 + infused cell dose on outcomes of patients undergoing allo-HCT following reduced intensity regimen for myelofibrosis: a study from the Chronic Malignancies Working Party of the EBMT.
- Author
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Czerw T, Iacobelli S, Malpassuti V, Koster L, Kröger N, Robin M, Maertens J, Chevallier P, Watz E, Poiré X, Snowden JA, Kuball J, Kinsella F, Blaise D, Reményi P, Mear JB, Cammenga J, Rubio MT, Maury S, Daguindau E, Finnegan D, Hayden P, Hernández-Boluda JC, McLornan D, and Yakoub-Agha I
- Subjects
- Adult, Aged, Humans, Middle Aged, Retrospective Studies, Transplantation Conditioning, Unrelated Donors, Young Adult, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Neoplasms etiology, Primary Myelofibrosis therapy
- Abstract
The optimal CD34 + cell dose in the setting of RIC allo-HCT for myelofibrosis (MF) remains unknown. We retrospectively analyzed 657 patients with primary or secondary MF transplanted with use of peripheral blood (PB) stem cells after fludarabine/melphalan or fludarabine/busulfan RIC regimen. Median patient age was 58 (range, 22-76) years. Donors were HLA-identical sibling (MSD) or unrelated (UD). Median follow-up was 46 (2-194) months. Patients transplanted with higher doses of CD34 + cells (>7.0 × 10
6 /kg), had an increased chance of achievement of both neutrophil (hazard ratio (HR), 1.46; P < 0.001) and platelet engraftment (HR, 1.43; P < 0.001). In a model with interaction, for patients transplanted from a MSD, higher CD34 + dose was associated with improved overall survival (HR, 0.63; P = 0.04) and relapse-free survival (HR, 0.61; P = 0.02), lower risk of non-relapse mortality (HR, 0.57; P = 0.04) and higher rate of platelet engraftment. The combined effect of higher cell dose and UD was apparent only for higher neutrophil and platelet recovery rate. We did not document any detrimental effect of high CD34 + dose on transplant outcomes. More bulky splenomegaly was an adverse factor for survival, engraftment and NRM. Our analysis suggests a potential benefit for MF patients undergoing RIC PB-allo-HCT receiving more than 7.0 × 106 /kg CD34 + cells., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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25. Correction: Idelalisib exposure before allogeneic stem cell transplantation in patients with follicular lymphoma: an EBMT survey.
- Author
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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
- Published
- 2021
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26. Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party.
- Author
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Hayden PJ, Eikema DJ, de Wreede LC, Koster L, Kröger N, Einsele H, Minnema M, Dominietto A, Potter M, Passweg J, Bermúdez A, Nguyen-Quoc S, Platzbecker U, Tischer J, Ciceri F, Veelken JH, Ljungman P, Schaap N, Forcade E, Carella AM, Gandemer V, Arcese W, Bloor A, Olivieri A, Vincent L, Beksac M, Schönland S, and Yakoub-Agha I
- Subjects
- Allografts, Humans, Neoplasm Recurrence, Local, Retrospective Studies, Transplantation Conditioning, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy
- Abstract
The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30-46%) at 2 years and 25% (17-32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24-46%); Others 9% (0-17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33-67%); Other 22% (8-36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21-40%) vs. 10% (1-20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24-0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting., (© 2021. The Author(s).)
- Published
- 2021
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27. Outcomes following second allogeneic haematopoietic cell transplantation in patients with myelofibrosis: a retrospective study of the Chronic Malignancies Working Party of EBMT.
- Author
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Nabergoj M, Mauff K, Robin M, Kröger N, Angelucci E, Poiré X, Passweg J, Radujkovic A, Platzbecker U, Robinson S, Rambaldi A, Petersen SL, Stölzel F, Stelljes M, Ciceri F, Mayer J, Ladetto M, de Wreede LC, Koster L, Hayden PJ, Czerw T, Hernández-Boluda JC, McLornan D, Chalandon Y, and Yakoub-Agha I
- Subjects
- Humans, Middle Aged, Retrospective Studies, Transplantation Conditioning, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Neoplasms, Primary Myelofibrosis therapy
- Abstract
Therapeutic management of patients with primary or secondary myelofibrosis (MF) who experience relapse or graft failure following allogeneic haematopoietic cell transplantation (allo-HCT) remains heterogeneous. We retrospectively analyzed 216 patients undergoing a second allo-HCT for either relapse (56%) or graft failure (31%) between 2010 and 2017. Median age was 57.3 years (range 51-63). The same donor as for the first allo-HCT was chosen in 66 patients (31%) of whom 19 received an HLA-identical sibling donor, whereas a different donor was chosen for 116 patients (54%). Median follow-up was 40 months. Three-year overall survival (OS) and relapse-free survival (RFS) were 42% and 39%, respectively. Three-year non-relapse mortality (NRM) and relapse rates were 36% and 25%, respectively. Grade II-IV and III-IV acute GVHD occurred in 25% and 11% of patients, respectively, and the 3-year incidence of chronic GVHD was 33% including 14% for extensive grade. Graft-failure incidence at 1 year was 14%. In conclusion, our data suggest that a second allo-HCT is a potential option for patients failing first allo-HCT for MF albeit careful patient assessment is fundamental to identify individual patients who could benefit from this approach., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2021
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28. Natural killer cell alloreactivity in HLA-haploidentical hematopoietic transplantation: a study on behalf of the CTIWP of the EBMT.
- Author
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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
- Subjects
- 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.)
- Published
- 2021
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29. Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT.
- Author
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Gagelmann N, Eikema DJ, de Wreede LC, Rambaldi A, Iacobelli S, Koster L, Caillot D, Blaise D, Remémyi P, Bulabois CE, Passweg J, Leleu X, Zver S, Kobbe G, Ljungman P, Chevallier P, Ringhoffer M, Martin M, Salmenniemi U, Poiré X, Lenhoff S, Pioltelli P, Mordini N, Delforge M, Garderet L, Schönland S, Yakoub-Agha I, and Kröger N
- Subjects
- Disease-Free Survival, Humans, Neoplasm Recurrence, Local, Stem Cell Transplantation, Transplantation, Autologous, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy
- Abstract
We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n = 446), auto-auto (n = 105), or auto-allo (n = 72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45-58%) for single auto, 60% (95% CI, 49-72%) for auto-auto, and 67% (95% CI, 53-80%) for auto-allo (p = 0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12-22%), 33% (95% CI, 22-43%), and 34% (95% CI, 21-38%; p = 0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p = 0.007) and auto-allo (HR, 0.45; p = 0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p = 0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p = 0.097). No significant difference in OS was identified between the groups in patients with del(17p).
- Published
- 2021
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30. Idelalisib exposure before allogeneic stem cell transplantation in patients with follicular lymphoma: an EBMT survey.
- Author
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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
- Subjects
- Humans, Purines, Quinazolinones, Hematopoietic Stem Cell Transplantation, Lymphoma, Follicular therapy
- Published
- 2020
- Full Text
- View/download PDF
31. Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia.
- Author
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Michallet M, Dreger P, Sobh M, Koster L, Hoek J, Boumendil A, Scheid C, Fox CP, Wulf G, Krüger W, van Gelder M, Corradini P, Russo D, Passweg J, Schoemans H, Bethge W, Schaap N, Cornelissen J, Browne P, Durakovic N, Muller L, Montoto S, Kroger N, and Schetelig J
- Subjects
- Adenine analogs & derivatives, Humans, Male, Piperidines, Retrospective Studies, Salvage Therapy, Hematopoietic Stem Cell Transplantation, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.
- Published
- 2020
- Full Text
- View/download PDF
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