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One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow Transplantation (EBMT) database. The median age at HSCT was 29 years (range, 1 to 66 years). The transplant donor was related in 49% cases and unrelated in 51% cases. The 5-year probability of relapse was 17%, and that of nonrelapse mortality was 41%. The 5-year overall survival was 45% ± 9%, better for patients untreated and patients in remission compared with patients with refractory disease. Our data indicate that allogeneic HSCT leads to prolonged survival in close to one-half of the patients transforming to MDS or AML from SAA. [ABSTRACT FROM AUTHOR]

The European society for Blood and Marrow Transplantation (EBMT) has a long-standing interest in the evaluation of hematopoietic cell transplantation. More than three decades ago, its members established a continental registry. Today, more than 700,000 patients have been registered, and information has been gathered on more than 800,000 transplants. This huge amount of information has allowed conducting multiple retrospective studies, evaluating changes in practices over time and for different categories of diseases, benchmarking outcome across EBMT affiliated centers, and increasingly serves to build synthetic comparators to evaluate the introduction of therapeutic innovations in the field of hematology. CAR-T cells therapies draw on human and technical resources that are also used to deliver HCT; they elicit side effects that require the implementation of risk mitigation plans; they are living drugs that persist in the body of the recipient and thus deserve prolonged follow-up; the introduction of CAR-T cells in the pharmacopeia is likely to significantly impact on the practice of BMT; for all these reasons and even before the first approvals of CAR-T Cells in Europe, EBMT engaged in a project aiming at complementing the EBMT Registry with a Cellular Therapy Form, with the objective to register CAR-T cells treated patients and collect information on their short-, middle- and long-term outcome. The goal is to provide EBMT investigators with a tool for primary analyses of the collected information and to support secondary use of data transferred at the individual level to Marketing Authorization Holders and other interested parties, to fulfill their obligations to health authorities and further evaluate the actual medical values of CAR-T Cells in different contexts and indications. The EBMT Registry received a positive opinion from the European Medicines agency in 2019, and five years later contains information on more than 9.000 treated patients. This article describes the journey to start this new activity, lessons to be drawn in view of improving the collection of real-world data, and what existing information tells us in terms of patient access., Competing Interests: Declaration of competing interest AvB, SvdW, AM, ISO, EMG are or have been permanent and paid employees with EBMT. CC, AR, SM, RdlC, PL, MM, NK, AS, CB & JK volunteer part of their professional time to contribute to EBMT missions and tasks, in different and temporary positions. In their different capacities, all co-authors have interacted with Pharma companies (including Novartis, Kite/Gilead, BMS, Janssen) that develop and commercialize CAR-T Cells and other advanced therapies to establish the European CAR-T Cells Registry described in this manuscript, and launch PASS and PAES. Interactions with Pharma companies as well as with other public or private, not-for profit or for-profit organizations is ongoing in the context of the GoCART Coalition. JK received funding from Novartis, Miltenyi Biotech, is a cofounder of Gadeta as well as shareholder of floow-up companies of Gadeta such as Century Therapeutics and Adeta., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Incidence and risk factors of second solid cancers (SSCs) that occur after hematopoietic stem cell transplantation (HSCT) are well documented. However, clinical outcome data of patients who developed an SSC after HSCT are limited., Objective: To assess the outcome of patients with an SSC occurring after HSCT from the time of SSC diagnosis., Design, Setting, and Participants: This cohort study used data of 4065 patients from 26 countries registered with the European Society for Blood and Marrow Transplantation, which has maintained clinical data since 1977 of patients who received a transplant. Information from all patients who underwent a transplant in Europe and had an SSC diagnosis between January 1, 2000, and December 31, 2014, was extracted. The cohort included patients with 18 different cancers. Data analysis was conducted from September 3, 2017, to March 17, 2018., Main Outcomes and Measures: Median and 5-year age-standardized overall survival, causes of death, risk factor multivariate analysis using a clustered Cox proportional hazard regression model, and standardized mortality ratio were calculated for each of the 18 types of SSC., Results: In total, 220 617 patients underwent a transplant, of whom only 4065 (1.8%) patients with a second solid cancer after HSCT were included in the study. Among the 4065 patients, 2321 (57.1%) were men and 1744 (42.9%) were women, with a mean (range) age of 59.1 (3.2-82.3) years at diagnosis of second solid cancer. The 5-year age-standardized overall survival was 47% (95% CI, 45%-49%). The 5-year overall survival rate after SSC diagnosis was poor for pancreas, lung, hepatobiliary, esophageal, brain, and gastric cancers, with a median survival between 0.6 and 1 year. The 5-year overall survival was intermediate for endometrial, colorectal, sarcomas, ovarian, bladder, oropharyngeal, and kidney cancers, with a median survival between 2 and 10 years. The 5-year overall survival was more favorable for melanoma, breast, prostate, cervix, and thyroid cancers, with a median survival of 10 or more years. Additional transplant-associated factors for mortality for patients treated with allogeneic HSCT were age at transplant, donor type, conditioning regimen, and graft-vs-host disease. In total, 1777 patients (43.7%) died, of which 1256 (74.8%) were from SSC, 344 (20.5%) from primary disease, and 79 (4.7%) from other causes. Standardized mortality ratio was higher, compared with de novo solid cancers, for melanoma, prostate, breast, kidney, bladder, colorectal, and endometrial cancers but not for the other cancers., Conclusions and Relevance: The outcome of SSC is mainly dependent on the type of second cancer; thus, future studies should investigate the reasons the standardized mortality ratio is higher for some cancers to identify whether patients with these cancers should be treated differently and to help in screening and counseling patients who developed an SSC after HSCT.

No standard exists for the treatment of myelodysplastic syndrome relapsing after allogeneic stem cell transplantation. We performed a retrospective registry analysis of outcomes and risk factors in 698 patients, treated with different strategies. The median overall survival from relapse was 4.7 months (95% confidence interval: 4.1-5.3) and the 2-year survival rate was 17.7% (95% confidence interval: 14.8-21.2%). Shorter remission after transplantation ( P <0.001), advanced disease ( P =0.001), older age ( P =0.007), unrelated donor ( P =0.008) and acute graft- versus -host disease before relapse ( P <0.001) adversely influenced survival. At 6 months from relapse, patients had received no cellular treatment, (i.e. palliative chemotherapy or best supportive care, n=375), donor lymphocyte infusion (n=213), or a second transplant (n=110). Treatment groups were analyzed separately because of imbalanced characteristics and difficulties in retrospectively evaluating the reason for individual treatments. Of the patients who did not receive any cellular therapy, 109 were alive at 6 months after relapse, achieving a median overall survival from this landmark of 8.9 months (95% confidence interval: 5.1-12.6). Their 2-year survival rate was 29.7%. Recipients of donor lymphocytes achieved a median survival from first infusion of 6.0 months (95% confidence interval: 3.7-8.3) with a 2-year survival rate of 27.6%. Longer remission after first transplantation ( P <0.001) and younger age ( P =0.009) predicted better outcome. Among recipients of a second transplant, the median survival from second transplantation was 4.2 months (95% confidence interval: 2.5-5.9), and their 2-year survival rate was 17.0%. Longer remission after first transplantation ( P <0.001), complete remission at second transplant ( P =0.008), no prior chronic graft- versus -host disease ( P <0.001) and change to a new donor ( P =0.04) predicted better outcome. The data enabled identification of patients benefiting from donor lymphocyte infusion and second transplantation, and may serve as a baseline for prospective trials., (Copyright© 2018 Ferrata Storti Foundation.)

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day +90) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken., (© 2015 by The American Society of Hematology.)

We have recently reported on the outcome of autologous transplantation in the rare myelomas (IgD, IgE, IgM, and nonsecretory [NS]) but there is no real information on the outcome of these conditions after allogeneic transplantation. We used the European Group for Blood and Marrow Transplantation myeloma database to compare the outcomes after allogeneic transplantation of 1354 common myelomas (IgG, IgA, and light chain myeloma) with the outcome in 26 IgD myelomas and 52 NS myelomas. There was little difference between common and the IgD and NS myeloma patients with respect to prognostic factors although the IgD group had a higher beta 2 microglobulin at diagnosis, shorter time to transplantation, and more T cell depletion. IgD and NS patients had a significantly greater achievement of complete remission at conditioning but this did not translate into equivalent progression-free survival and overall survival for the IgD patients although the NS outcome was very similar to that of common myeloma. The PFS and OS of IgD, common, and NS myelomas appear similar after allogeneic transplantation, despite a tendency for higher early relapse rate in IgD myeloma. Allogeneic transplantation may, therefore, be an option to investigate in prospective observational studies., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

This study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0-12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen-matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18). Event-free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0·001). Ninety-one of 167 patients (55%) failed front-line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up-front (P 0·017). Rejection was 2% for MFD HSCT and HSCT post-IST failure (P 0·73). Acute graft-versus-host disease (GVHD) grade II-IV was 8% in MFD graft vs. 25% for HSCT post-IST failure (P < 0·0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post-IST failure (P < 0·0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first-line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option., (© 2015 John Wiley & Sons Ltd.)

The aim of this study was to determine the impact of the revised 5-group International Prognostic Scoring System cytogenetic classification on outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia who were reported to the European Society for Blood and Marrow Transplantation database. A total of 903 patients had sufficient cytogenetic information available at stem cell transplantation to be classified according to the 5-group classification. Poor and very poor risk according to this classification was an independent predictor of shorter relapse-free survival (hazard ratio 1.40 and 2.14), overall survival (hazard ratio 1.38 and 2.14), and significantly higher cumulative incidence of relapse (hazard ratio 1.64 and 2.76), compared to patients with very good, good or intermediate risk. When comparing the predictive performance of a series of Cox models both for relapse-free survival and for overall survival, a model with simplified 5-group cytogenetics (merging very good, good and intermediate cytogenetics) performed best. Furthermore, monosomal karyotype is an additional negative predictor for outcome within patients of the poor, but not the very poor risk group of the 5-group classification. The revised International Prognostic Scoring System cytogenetic classification allows patients with myelodysplastic syndromes to be separated into three groups with clearly different outcomes after stem cell transplantation. Poor and very poor risk cytogenetics were strong predictors of poor patient outcome. The new cytogenetic classification added value to prediction of patient outcome compared to prediction models using only traditional risk factors or the 3-group International Prognostic Scoring System cytogenetic classification., (Copyright© Ferrata Storti Foundation.)

Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with higher risk myelodysplastic syndrome (MDS), but the choice of the optimal alternative stem cell source is still a subject of debate in patients lacking an HLA-matched sibling donor. Here, we report on a large series of patients with MDS (N = 631) transplanted either with mobilized peripheral stem cells (PBs) from unrelated donors (n = 502) or with umbilical cord blood transplant (UCB, n = 129) as alternative grafts after reduced-intensity conditioning. Neutrophil engraftment was higher after PB (98% versus 78%, P < .0001). Acute graft-versus-host disease (GVHD) was similar after PB (31%) and UCB (29%), and chronic GVHD incidence was higher after PB (41% versus 23%). Two-year nonrelapse mortality was lower after PB (31% versus 42% P = .03). There was a better overall survival (OS) and disease-free survival (DFS) after PB (49% ± 2% versus 30% ± 4%, P < .0001 and 44% ± 2% versus 28% ± 4%, P < .0001). Multivariate analysis confirmed the advantage of PB for treatment-related mortality, OS, and DFS, whereas relative risk of chronic GVHD was similar. A multivariate analysis comparing PB from a 10/10 HLA-matched donor, PB from a 9/10 HLA-matched donor, and UCB showed an advantage on treatment-related mortality, DFS, and OS only in 10/10 PB. We conclude that in MDS patients lacking an HLA-matched sibling donor, PB from a 10/10 HLA-matched unrelated donor is the preferred source of hematopoietic stem cells. HLA-mismatched unrelated donor or cord blood seem to give similar inferior results except for neutrophil engraftment, which is delayed after UCB., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Dimethyl sulfoxide (DMSO) is essential for the preservation of liquid nitrogen-frozen stem cells, but is associated with toxicity in the transplant recipient., Study Design and Methods: In this prospective noninterventional study, we describe the use of DMSO in 64 European Blood and Marrow Transplant Group centers undertaking autologous transplantation on patients with myeloma and lymphoma and analyze side effects after return of DMSO-preserved stem cells., Results: While the majority of centers continue to use 10% DMSO, a significant proportion either use lower concentrations, mostly 5 or 7.5%, or wash cells before infusion (some for selected patients only). In contrast, the median dose of DMSO given (20 mL) was much less than the upper limit set by the same institutions (70 mL). In an accompanying statistical analysis of side effects noted after return of DMSO-preserved stem cells, we show that patients in the highest quartile receiving DMSO (mL and mL/kg body weight) had significantly more side effects attributed to DMSO, although this effect was not observed if DMSO was calculated as mL/min. Dividing the myeloma and lymphoma patients each into two equal groups by age we were able to confirm this result in all but young myeloma patients in whom an inversion of the odds ratio was seen, possibly related to the higher dose of melphalan received by young myeloma patients., Conclusion: We suggest better standardization of preservation method with reduced DMSO concentration and attention to the dose of DMSO received by patients could help reduce the toxicity and morbidity of the transplant procedure., (© 2014 AABB.)

Transformed acute myeloid leukemia in myelofibrosis results in a median survival of less than 5 months. We identified 46 of 1048 myelofibrosis patients in the European Group for Blood and Marrow Transplantation registry who received allogeneic stem cell transplantation for acute leukemia evolving from myelofibrosis. The cumulative incidence of treatment-related mortality at 1 year was 28% (95% confidence interval, 14 to 42) and of relapse at 3 years was 47% (95% confidence interval, 31 to 63). The 3-year progression-free (PFS) and overall survival (OS) rates were 26% and 33%, respectively. The only significant factor for survival was complete remission versus no complete remission before transplantation (69% versus 22%, P = .008); however, complete remission was achieved only in 8 patients. Allogeneic stem cell transplantation can cure myelofibrosis patients transformed to leukemia., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background:  The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting., Methods:  A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease., Results:  One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival., Conclusions:  More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.

Purpose: Patients with chronic lymphocytic leukemia (CLL) and 17p deletion (17p-) have a poor prognosis. Although allogeneic hematopoietic stem-cell transplantation (HCT) has the potential to cure patients with advanced CLL, it is not known whether this holds true for patients with 17p-CLL., Patients and Methods: Baseline data from patients, for whom information on the presence of 17p-CLL was available, were downloaded from the European Group for Blood and Marrow Transplantation database. Additional information on the course of CLL and follow-up was collected with a questionnaire., Results: A total of 44 patients with 17p-CLL received allogeneic HCT between March 1995 and July 2006 from a matched sibling (n = 24) or an alternative donor (n = 20). 17p-CLL had been diagnosed by fluorescent in situ hybridization in 82% of patients and by conventional banding in 18% of patients. The median age was 54 years. Before HCT, a median of three lines of chemotherapy had been administered. At HCT, 53% of patients were in remission. Reduced-intensity conditioning was applied in 89% of patients. Acute, grade 2 to 4 graft-versus-host disease (GVHD) occurred in 43% of patients, and extensive chronic GVHD occurred in 53% of patients. At last follow-up, 19 patients were alive, with a median observation time of 39 months (range, 18 to 101 months). Three-year overall survival and progression-free survival rates were 44% and 37%, respectively. The cumulative incidence of progressive disease at 4 years was 34%. No late relapse occurred in nine patients with a follow-up longer than 4 years., Conclusion: Allogeneic HCT has the potential to induce long-term disease-free survival in patients with 17p-CLL.