Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT

Allogeneic hematopoietic stem cell transplantation (HCT) may result in long-term disease control in high-risk chronic lymphocytic leukemia (CLL). Recently, haploidentical HCT is gaining interest because of better outcomes with post-transplantation cyclophosphamide (PTCY). We analyzed patients with CLL who received an allogeneic HCT with a haploidentical donor and whose data were available in the EBMT registry. In total 117 patients (74% males) were included; 38% received PTCY as GVHD prophylaxis. For the whole study cohort OS at 2 and 5 yrs was 48 and 38%, respectively. PFS at 2 and 5 yrs was 38 and 31%, respectively. Cumulative incidence (CI) of NRM in the whole group at 2 and 5 years were 40 and 44%, respectively. CI of relapse at 2 and 5 yrs were 22 and 26%, respectively. All outcomes were not statistically different in patients who received PTCY compared to other types of GVHD prophylaxis. In conclusion, results of haploidentical HCT in CLL seem almost identical to those with HLA-matched donors. Thereby, haploidentical HCT is an appropriate alternative in high risk CLL patients with a transplant indication but no available HLA-matched donor. Despite the use of PTCY, the CI of relapse seems not higher than observed after HLA-matched HCT

Fludarabine-treosulfan versus fludarabine-melphalan or busulfan-cyclophosphamide conditioning in older AML or MDS patients – A clinical trial to registry data comparison

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

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

Non peer reviewe

Post-Transplantation Cyclophosphamide for Graft-versus- Host Disease Prophylaxis in Multiple Myeloma Patients Who Underwent Allogeneic Hematopoietic Cell Transplantation:First Comparison by Donor Type. A Study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Graft-versus-host disease (GVHD) remains among the major causes of treatment failure in patients with multiple myeloma (MM) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The use of post-transplantation cyclophosphamide (PT-Cy) is now a well-established and widely used method for GVHD prophylaxis after HLA haploidentical HCT. However, the rationale for using PT-Cy in the setting of matched donor transplantation is less apparent, given the lesser degree of bidirectional alloreactivity. In this retrospective study, we investigated the role of PT-Cy as GVHD prophylaxis in patients with multiple myeloma underoing allo-HCT, among different donor types, to determine cumulative incidence of acute and chronic GVHD and impact on engraftment, progression-free survival (PFS), GVHD-free/relapse- free survival (GRFS), overall survival (OS), and NRM A total of 295 patients with MM underwent allo-HCT using grafts from a matched related donor (MRD; n = 67), matched unrelated donor (MUD; n = 72), mismatched related or unrelated donor (MMRD/MMUD, 1 antigen; n = 27), or haploidentical donor (haplo; n = 129) using PT-Cy between 2012 and 2018. In addition to PT-Cy, agents used in GVHD prophylaxis included calcineurin inhibitors in 239 patients (81%), with mycophenolate mofetil in 184 of those 239 (77%). For grade II-IV acute GVHD, the cumulative incidence at day +100 was 30% (95% confidence interval [CI], 25% to 36%), 9% (95% CI, 5% to 12%) for grade III-IV acute GVHD, and 27% (95% CI, 21% to 32%) for chronic GVHD (limited, 21%; extensive, 6%), with no differences by donor type. The median time to neutrophil engraftment was 19d (95% CI, 18-19), with no significant difference by donor type. The median time to platelet engraftment was delayed in haploidentical donor graft recipients (27 days versus 21 days; P <.001). Two-year OS, PFS, GRFS, and NRM were 51% (95% CI, 45% to 58%), 26% (95% CI, 20% to 32%), 24% (95% CI, 18% to 30%), and 19% (95% CI, 14% to 24%), respectively, with no significant difference between different donor types. In multivariable analyses, compared with the haplo donors, the use of MRDs was associated with significantly better OS (hazard ratio [HR], 0.6; 95% CI, 0.38 to 0.95; P =.029), and the use of MUDs was associated with a significantly higher GRFS (HR, 0.63; 95% CI, 0.42 to 0.97; P =.034). There was a trend toward improved PFS with use of MUDs (HR, 0.69; 95% CI, 0.46 to 1.04; P =.08). Our data show that PT-Cy in MM patients undergoing allo-HCT resulted in low rates of acute and chronic GVHD and led to favorable survival, especially in the matched related donor setting

Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis

Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events Aoccur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64% (60-68%) and overall survival was 74% (71-78%) at ten years; results were better in younger individuals and in women. Excess mortality was 14% (8-21%) in patients aged = 65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors.Peer reviewe

Stem cell transplantation for congenital dyserythropoietic anemia : an analysis from the European Society for Blood and Marrow Transplantation

Non peer reviewe

Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity: an EBMT IEWP study.

peer reviewedAllogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT

Haplo-identical or mismatched unrelated donor hematopoietic cell transplantation for Fanconi anemia: Results from the Severe Aplastic Anemia Working Party of the EBMT

Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for bone marrow failure or hematopoietic malignant diseases for Fanconi anemia (FA) patients. Although results have improved over the last decades, reaching more than 90% survival when a human leukocyte antigen (HLA)-identical donor is available, alternative HCT donors are still less reported. We compared HCT outcomes using HLA-mismatched unrelated donors (MMUD; n = 123) or haplo-identical donors (HDs), either using only in vivo T cell depletion (n = 33) or T cells depleted in vivo with some type of graft manipulation ex vivo (n = 59) performed for FA between 2000 and 2018. Overall survival (OS) by 24 months was 62% (53-71%) for MMUD, versus 80% (66-95%) for HDs with only in vivo T cell depletion and 60% (47-73%) for HDs with in vivo and ex vivo T cell depletion (p = .22). Event-free survival (EFS) was better for HD-transplanted FA patients with only in vivo T cell depletion 86% (73-99%) than for those transplanted from a MMUD 58% (48-68%) or those with graft manipulation 56% (42-69%) (p = .046). Grade II-IV acute graft-versus-host disease (GVHD) was 41% (MMUD) versus 40% (HDs with no graft manipulation) versus 17% (HDs with T cell depleted graft), (p = .005). No differences were found for the other transplant related outcomes. These data suggest that HDs might be considered as an alternative option for FA patients with better EFS using unmanipulated grafts

Comparison of outcomes for HLA-matched sibling and haplo identical donors in Myelodysplastic syndromes: report from the chronic malignancies working party of EBMT

Myelodysplastic syndromes (MDS) are the second common indication for an Allo-HCT. We compared the outcomes of 1414 matched sibling (MSD) with 415 haplo-identical donors (HD) transplanted with post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis between 2014 and 2017. The median age at transplant with MSD was 58 and 61 years for HD. The median time to neutrophil engraftment was longer for HD being 20 vs 16 days for MSD (p < 0.001). Two-year overall survival (OS) and PFS (progression free survival) with MSD were significantly better at 58% compared with 50%, p ≤ 0.001, and 51% vs 47%, p = 0.029, with a HD. Relapse at 2 years was lower with a HD 23% than with MSD 29% (p = 0.016). Non relapse mortality (NRM) was higher with HD in the first 6 months post-transplant [HR 2.59 (1.5–4.48) p < 0.001] and was also higher at 2 years being 30% for HD and 20% for MSD, p ≤ 0.001. The incidence of acute GVHD grade II-IV and III–IV at 100 days was comparable for MSD and HD, however, chronic GVHD at 2 years was significantly higher with MSD being 44% vs 32% for HD (p < 0.001). After multivariable analysis, OS and primary graft failure were significantly worse for HD particularly before 6 months [HR 1.93(1.24–3.0)], and HR [3.5(1.5–8.1)]. The median age of HD 37 (IQR 30–47) years was significantly lower than sibling donors 56 (IQR 49–62 years) p < 0.001. However, there was no effect on NRM, relapse or PFS. This data set suggests that a MSD donor remains the preferred choice in MDS over a haplo donor. Transplants with haploidentical donors result in satisfactory long-term outcome, justifying it’s use when no better donor is available

SARS-CoV-2 vaccination in 361 non-transplanted patients with aplastic anemia and/or paroxysmal nocturnal hemoglobinuria

We thank the support of the Severe Aplastic Anemia and Infectious Disease working parties of the EBMT and the patients for participation