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1.
Outcomes of CMML patients undergoing allo-HCT are significantly worse compared to MDS-a study of the CMWP of the EBMT
Rovó, A., Gras, L., Piepenbroek, B., Kröger, N., Reinhardt, H. C., Radujkovic, A., Blaise, D., Kobbe, G., Niityvuopio, R., Platzbecker, U., et al
American journal of hematology. 2024;99(2):203-215
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Abstract
Although CMML since long has been separated from MDS, many studies continue to evaluate the outcomes of both diseases after hematopoietic cell transplantation (allo-HCT) together. Data evaluating outcomes of a large CMML cohort after allo-HCT compared to MDS are limited. We aim to compare outcomes of CMML to MDS patients who underwent allo-HCT between 2010 and 2018. Patients ≥18 years with CMML and MDS undergoing allo-HCT reported to the EBMT registry were analyzed. Progression to AML before allo-HCT was an exclusion criterion. Overall survival (OS), progression/relapse-free survival (PFS), relapse incidence (including progression) (REL), and non-relapse mortality (NRM) were evaluated in univariable and multivariable (MVA) Cox proportional hazard models including interaction terms between disease and confounders. In total, 10832 patients who underwent allo-HCT were included in the study, there were a total of 1466 CMML, and 9366 MDS. The median age at time of allo-HCT in CMML (median 60.5, IQR 54.3-65.2 years) was significantly higher than in the MDS cohort (median 58.8, IQR 50.2-64.5 years; p < .001). A significantly higher percentage of CMML patients were male (69.4%) compared to MDS (61.2%; p < .001). There were no clinically meaningful differences in the distribution of Karnofsky score, Sorror HCT-CI score at allo-HCT, and donor type, between the CMML and MDS patients. RIC platforms were utilized in 63.9% of CMML allo-HCT, and in 61.4% of MDS patients (p = .08). In univariable analyses, we found that OS, PFS, and REL were significantly worse in CMML when compared with MDS (all p < .0001), whereas no significant difference was observed in NRM (p = .77). In multivariable analyses, the HR comparing MDS versus CMML for OS was 0.81 (95% CI, 0.74-0.88, p < .001), PFS 0.76 (95% CI 0.70-0.82, p < .001), relapse 0.66 (95% CI 0.59-0.74, p < .001), and NRM 0.87 (95% CI 0.78-0.98, p = .02), respectively. The association between baseline variables and outcome was found to be similar in MDS and CMML (all interaction p > .05) except for a decreasing trend over time of the risk of relapse in CMML (HR allo-HCT per year later 0.94, 95% CI 0.90-0.98), whereas no such trend was observed in MDS (HR 1.00, 95% CI 0.98-1.02). The poor outcome observed for CMML could be related to variables not measured in this study or to factors inherent to the disease itself. This study demonstrates that outcomes of CMML patients after allo-HCT are significantly worse compared to MDS. The results of this study may contribute to future recommendations for allo-HCT in CMML patients.
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2.
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
Giebel, S., Labopin, M., Houhou, M., Caillot, D., Finke, J., Blaise, D., Fegueux, N., Ethell, M., Cornelissen, J. J., Forcade, E., et al
Bone marrow transplantation. 2023;58(4):393-400
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.
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3.
Comorbidities in recipients of low transplant conditioning intensity regimens for acute myeloid leukemia: an ALWP EBMT study
Fein, J. A., Shouval, R., Galimard, J. E., Labopin, M., Socié, G., Finke, J., Cornelissen, J. J., Malladi, R., Itälä-Remes, M., Chevallier, P., et al
Blood advances. 2023
Abstract
Older age and high burden of comorbidities often drive selection of low-intensity conditioning regimens in allogeneic-hematopoietic stem cell transplantation (HSCT) recipients. However, the impact of comorbidities in the low-intensity conditioning setting is unclear. We sought to determine the contribution of individual comorbidities and their cumulative burden on the risk of non-relapse mortality (NRM) in patients receiving low-intensity regimens. In a retrospective analysis of adults (≥ 18 years) transplanted for acute myeloid leukemia (AML) in first complete remission (CR) between 2008-2018, we studied recipients of low-intensity regimens as defined by the Transplantation Conditioning Intensity (TCI) scale. Multivariable Cox models were constructed to study associations of comorbidities with NRM. Comorbidities identified as putative risk factors in the low-TCI setting were included in combined multivariable regression models assessed for overall survival, NRM, and relapse. A total of 1,663 patients with a median age of 61 years received low-TCI regimens. Cardiac comorbidity (including arrhythmia/valvular disease) and psychiatric disease were associated with increased NRM risk (hazard ratio [HR] 1.54 [95% CI 1.13, 2.09] and 1.69 [1.02, 2.82], respectively). Moderate pulmonary dysfunction, though prevalent, was not associated with increased NRM. In a combined model, cardiac, psychiatric, renal, and inflammatory bowel disease were independently associated with adverse transplantation outcomes. These findings may inform patient and regimen selection and reinforce the need for further investigation of cardioprotective transplantation approaches.
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Primary Cancer Matters in Therapy-related Myeloid Neoplasm Patients Receiving Allogeneic Hematopoietic Cell Transplantation: A Study From the Chronic Malignancies Working Party of the EBMT
Robin, M., de Wreede, L. C., Schroeder, T., Stölzel, F., Kröger, N., Koster, L., Platzbecker, U., Finke, J., Ganser, A., Blaise, D., et al
HemaSphere. 2023;7(4):e851
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5.
Cord blood transplantation for adult lymphoid neoplasms in Europe and Japan
Watanabe, M., Kanda, J., Volt, F., Ruggeri, A., Suzuki, R., Rafii-Elayoubi, H., Kimura, F., Cappelli, B., Kondo, E., Scigliuolo, G. M., et al
Blood advances. 2023
Abstract
With the aim of identifying the different characteristics and prognostic factors of cord blood transplantation (CBT) in adult patients with lymphoid neoplasms in Europe and Japan, we conducted a collaborative study between European and Japanese registries. Patients aged 18-75 years receiving their first CBT (Europe: single CBT, n=192; double CBT, n=304; Japan: single CBT, n=1150) in 2000-2017 were analyzed. The number of patients with Hodgkin's lymphoma was higher in Europe (26% vs 5%) while that with mature T/NK-cell neoplasms was higher in Japan (20% vs 35%). The Japanese cohort comprised more elderly patients (>=50) (59% vs 39%) with higher refined disease risk index (rDRI) (high-very high: 49% vs 14%). High-very high rDRI (vs. low rDRI) was associated with inferior OS in common (Europe: HR 1.87 p=0.001; Japan: HR 2.34, p<0.001) with higher progression/relapse risks (Europe: HR 2.04, p=0.007; Japan: HR 2.96, p<0.001). Total body irradiation (TBI)-containing conditioning regimens contributed to superior OS both in Europe (vs TBI-RIC, non TBI-RIC: HR 1.93, p<0.001; non TBI-MAC: HR 1.90, p=0.003) and in Japan (non TBI-RIC: HR 1.71, p<0.001; non TBI-MAC: HR 1.50, p=0.007). The impact of HLA mismatches (>=2) on OS differed (Europe: HR 1.52, p=0.007; Japan: HR 1.18, p=0.107). Despite the different patient-disease-transplant characteristics, poor survival of patients receiving CBT for lymphoid neoplasms, especially in those with high rDRI was observed in both registries. The different impact of HLA mismatches on survival in the two registries calls attention to the fundamental differences among these populations. TBI should be considered in conditioning regimens.
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6.
Trends in autologous stem cell transplantation for newly diagnosed multiple myeloma: Changing demographics and outcomes in European Society for Blood and Marrow Transplantation centres from 1995 to 2019
Swan, D., Hayden, P. J., Eikema, D. J., Koster, L., Sauer, S., Blaise, D., Nicholson, E., Rabin, N., Touzeau, C., Byrne, J., et al
British journal of haematology. 2022
Abstract
Multiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy-based induction fell significantly, being largely replaced by bortezomib-based regimens. The two-year complete response rate increased from 22% to 42%. The five-year progression-free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm.
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Prognostic value of CPSS cytogenetic risk classification in patients with CMML after allogeneic hematopoietic cell transplantation: a retrospective multicenter study of the Chronic Malignancies Working Party of the EBMT
Koenecke, C., Eikema, D. J., Hazelaar, S., Schroeder, T., Potter, V., Kröger, N., Bornhäuser, M., Finke, J., Platzbecker, U., Radujkovic, A., et al
Bone marrow transplantation. 2022;57(10):1607-1611
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8.
Graft-Versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation
Nagler, A., Labopin, M., Dholaria, B., Wu, D., Choi, G., Aljurf, M., Ciceri, F., Gedde-Dahl, T., Meijer, E., Niittyvuopio, R., et al
Transplantation and cellular therapy. 2021
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Editor's Choice
Abstract
Cyclosporine A and methotrexate (CSA/MTX) is the standard graft-versus-host disease (GVHD) prophylaxis regimen for matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). Recently, post-transplant cyclophosphamide (PTCy) has been shown to be effective in GVHD prevention. In this registry-based study, we compared outcomes of 118 patients with PTCy and 1202 patients with CSA/MTX who underwent MSD allo-HCT for acute myeloid leukemia (AML). In a matched-pair analysis, PTCy was associated with a higher incidence of relapse at 2-year (41.1% versus 21.3%, p=0.039) compared to CSA/MTX. The incidence of day 180 grade II-IV acute GVHD (25.2% versus 25.4%, p=0.90) and 2-year chronic GVHD (42.6% versus 42.6%, p=0.84) were comparable between PTCy and CSA/MTX, respectively. Similarly, 2-year leukemia-free survival (LFS, 54.4% versus 74.32%, p=0.052), overall survival (OS, 70.6% versus 79.7%, p=0.15) and GVHD-free-relapse-free survival (GRFS, 38.1% versus 52.5%, p=0.49) were not statistically different between PTCy versus CSA/MTX. In conclusion, GVHD prophylaxis with PTCy is feasible, resulting in similar incidences of GVHD, GRFS, LFS, and OS compared to conventional CSA/MTX in patients undergoing allo-HCT from MSD. The higher relapse observed with PTCy needs further evaluation in a prospective study.
PICO Summary
Population
Patients who underwent matched sibling donor (MSD) allogeneic transplant for acute myeloid leukemia, (AML) reported to the EBMT registry (n=1320)
Intervention
Post-transplant cyclophosphamide (PTCy, n=118)
Comparison
Cyclosporine A and methotrexate (CSA/MTX, n=1202)
Outcome
In a matched-pair analysis, PTCy was associated with a higher incidence of relapse at 2-year (41.1% versus 21.3%) compared to CSA/MTX. The incidence of day 180 grade II-IV acute GVHD (25.2% versus 25.4%) and 2-year chronic GVHD (42.6% versus 42.6%) were comparable between PTCy and CSA/MTX, respectively. Similarly, 2-year leukemia-free survival (LFS, 54.4% versus 74.32%), overall survival (OS, 70.6% versus 79.7%) and GVHD-free-relapse-free survival (GRFS, 38.1% versus 52.5%) were not statistically different between PTCy versus CSA/MTX. In conclusion, GVHD prophylaxis with PTCy is feasible, resulting in similar incidences of GVHD, GRFS, LFS, and OS compared to conventional CSA/MTX in patients undergoing allo-HCT from MSD. The higher relapse observed with PTCy needs further evaluation in a prospective study.
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Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: a study of the Chronic Malignancies Working Party of EBMT and the Spanish Myelofibrosis Registry
Hernández-Boluda, J. C., Pereira, A., Kröger, N., Cornelissen, J. J., Finke, J., Beelen, D., de Witte, M., Wilson, K., Platzbecker, U., Sengeloev, H., et al
American journal of hematology. 2021
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly used in older myelofibrosis (MF) patients, but its risk/benefit ratio compared to non-transplant approaches has not been evaluated in this population. We analyzed the outcomes of allo-HCT in 556 MF patients aged > 65?years from the EBMT registry, and determined the excess mortality over the matched general population of MF patients > 65?years managed with allo-HCT (n=556) or conventional drug treatment (n=176). The non-transplant cohort included patients with intermediate-2 or high risk DIPSS from the Spanish Myelofibrosis Registry. After a median follow-up of 3.4?years, the estimated 5-year survival rate, non-relapse mortality (NRM), and relapse incidence after transplantation was 40%, 37%, and 25%, respectively. Busulfan-based conditioning was associated with decreased mortality (HR: 0.7, 95% CI: 0.5-0.9) whereas the recipient CMV+/donor CMV- combination (HR: 1.7, 95% CI: 1.2-2.4) and the JAK2 mutated genotype (HR: 1.9, 95% CI: 1.1-3.5) predicted higher mortality. Busulfan-based conditioning correlated with improved survival due to less NRM, despite its higher relapse rate when compared with melphalan-based regimens. Excess mortality was higher in transplanted patients than in the non-HCT cohort in the first year of follow-up (ratio: 1.93, 95% CI: 1.13-2.80), whereas the opposite occurred between the 4th and 8th follow-up years (ratio: 0.31, 95% CI: 0.18-0.53). Comparing the excess mortality of the two treatments, male patients seemed to benefit more than females from allo-HCT, mainly due to their worse prognosis with non-transplant approaches. These findings could potentially enhance counseling and treatment decision-making in elderly transplant-eligible MF patients. This article is protected by copyright. All rights reserved.
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Allogeneic hematopoietic stem cell transplantation for adult patients with t(4;11)(q21;q23) KMT2A/AFF1 B-cell precursor acute lymphoblastic leukemia in first complete remission: impact of pretransplant measurable residual disease (MRD) status. An analysis from the Acute Leukemia Working Party of the EBMT
Esteve, J., Giebel, S., Labopin, M., Czerw, T., Wu, D., Volin, L., Socié, G., Yakoub-Agha, I., Maertens, J., Cornelissen, J. J., et al
Leukemia. 2021
Abstract
Adult B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with t(4;11)(q21;q23);KMT2A/AFF1 is a poor-prognosis entity. This registry-based study was aimed to analyze outcome of patients with t(4;11) BCP-ALL treated with allogeneic hematopoietic stem cell transplantation (alloHSCT) in first complete remission (CR1) between 2000 and 2017, focusing on the impact of measurable residual disease (MRD) at the time of transplant. Among 151 patients (median age, 38) allotransplanted from either HLA-matched siblings or unrelated donors, leukemia-free survival (LFS) and overall survival (OS) at 2 years were 51% and 60%, whereas relapse incidence (RI) and non-relapse mortality (NRM) were 30% and 20%, respectively. These results were comparable to a cohort of contemporary patients with diploid normal karyotype (NK) BCP-ALL with equivalent inclusion criteria (n?=?567). Among patients with evaluable MRD pre-alloHSCT, a negative status was the strongest beneficial factor influencing LFS (hazard ratio [HR]?=?0.2, p?0.001), OS (HR?=?0.14, p?0.001), RI (HR?=?0.23, p?=?0.001), and NRM (HR?=?0.16, p?=?0.002), with a similar outcome to MRD-negative NK BCP-ALL patients. In contrast, among patients with detectable pretransplant MRD, outcome in t(4;11) BCP-ALL was inferior to NK BCP-ALL (LFS: 27% vs. 50%, p?=?0.02). These results support indication of alloHSCT in CR1 for t(4;11) BCP-ALL patients, provided a negative MRD status is achieved. Conversely, pre-alloHSCT additional therapy is warranted in MRD-positive patients.