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

Busulfan/Fludarabine- or Treosulfan/Fludarabine-Based Conditioning Regimen for Patients with Wiskott-Aldrich Syndrome – an EBMT Inborn Errors Working Party and Scetide Study

Introduction Excellent survival rates have been reported after allogeneic haematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS) patients. Recipient age >5 years in MUD HSCT as well as MMFD as donor were negative predictors for outcome. However, the vast majority of HSCTs in previously published studies were performed with (oral) busulfan/cyclophosphamide-based conditioning and in the early 2000 years or before. Objectives To compare OS and EFS after HSCT with either busulfan/fludarabine (BuFlu) ± thiotepa (TT) or treosulfan/fludarabine (TreoFlu) ± TT as recommended for primary immunodeficiencies since 2005 by the inborn errors working party (IEWP) of EBMT and ESID. Methods We performed a retrospective analysis via the EBMT and SCETIDE registries of WAS patients transplanted between 20006 and 2016 with these two regimens. At the time of this interim analysis, 174 patients were included, 92 (53%) with BuFlu±TT and 82 (47%) with TreoFlu±TT conditioning, with a median age of 1.6 years (0.2-30) at HSCT and a median follow-up of 32.9 months (1.5-128.9). Donors were MSD in 30, other MRD in 5, MUD (9/10 or 10/10) in 105, MMUD ( Results Two year overall survival (OS) of the entire cohort was 88.6% (95% c.i. 83.5%-93.6%). There was no significant difference in OS between BuFlu±TT or TreoFlu±TT conditioning (2-year OS 88.1% vs. 89.5%; p=0.7). Patients aged >5 years had a worse OS as compared to those 5 years or younger at HSCT (74.9% vs. 90.8%; p=0.005). The type of donor had no influence on OS: 96.4% for MSD/MFD, 86.8% for MUD/MMUD and 87.7% for MMFD (p=0.4). The rate of complete (≥90%) donor chimerism at last follow-up or before a secondary procedure (if a patient had one) was 41/42 (98%) in the BuFlu±TT group and 21/35 (60%) in the TreoFlu±TT group (p=0.0001). Twenty-six patients required a second procedure: stem cell boost in 4, donor lymphocyte infusion in 9, 2nd HSCT in 15 and splenectomy in 1. The 2-year cumulative incidence (CI) of second procedures was higher at 33.9% in the TreoFlu±TT versus 12.8% in the BuFlu±TT group (p=0.017), and 2-year EFS (events: second procedure or death) was 61.4% in the TreoFlu±TT and 75.0% in the BuFlu±TT group (p=0.2). Grade II-IV acute GVHD had the same incidence in both groups (24.4% vs. 26.3%; p=0.849) and chronic GVHD of any grade was borderline more frequent in the TreoFlu±TT group (17.2% vs 6.7%; p=0.054). Conclusion HSCT with either BuFlu±TT or TreoFlu±TT conditioning reliably cures almost 90% of patients with WAS regardless of donor type. Age >5 years at HSCT remains a negative risk factor. More patients were mixed chimeras and required second procedures after TreoFlu±TT than after BuFlu±TT conditioning. These data confirm the feasibility and efficacy of the regimens currently recommended by the IEWP

Hematopoietic cell transplantation in chronic granulomatous disease: a study of 712 children and adults

Gungor, Tayfun/0000-0002-3261-1186; Wang, Junfeng/0000-0001-5157-5355WOS: 000571446600014PubMed: 32614953Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can cure the disease, but the indication to transplant remains controversial. We performed a retrospective multicenter study of 712 patients with CGD who underwent allo-HCT transplantation from March 1993 through December 2018. We studied 635 children (aged = 18 years were 76% and 69%, respectively. Use of 1-antigen-mismatched donors was associated with reduced OS and EFS . No significant difference was found in OS, but a significantly reduced EFS was noted in the small group of patients who received a transplant from a donor with a >1 antigen mismatch. Choice of conditioning regimen did not influence OS or EFS. in summary, we report an excellent outcome after allo-HCT in CGD, with low incidence of graft failure and mortality in all ages. Older patients and recipients of 1-antigen-mismatched grafts had a less favorable outcome. Transplantation should be strongly considered at a younger age and particularly in the presence of a well-matched donor

Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT inborn errors working party analysis

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients transplanted at EBMT centers between 2006 and 2017, who received conditioning as recommended by the inborn errors working party (IEWP): either busulfan (n=103) or treosulfan (n=94) combined with fludarabine ± thiotepa. After a median follow-up after HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7%, and chronic GVHD-free survival (CRFS; events: death, graft failure, severe chronic GVHD) of 81.7%. Overall survival and CRFS were not significantly impacted by conditioning regimen (busulfan- versus treosulfan-based), donor type (MSD/MFD vs MUD/MMUD vs. MMFD), and period of HSCT (2006-2013 vs. 2014-2017). Patients younger than 5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III-IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure, mixed donor chimerism and more frequently received secondary procedures (2nd HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival

Allogeneic hematopoietic stem cell transplantation in leukocyte adhesion deficiency type I and III

Type I and III leukocyte adhesion deficiencies (LADs) are primary immunodeficiency disorders resulting in early death due to infections and additional bleeding tendency in LAD-III. The curative treatment of LAD-I and LAD-III is allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this retrospective multicenter study, data were collected using the European Society for Blood and Marrow Transplantation registry; we analyzed data from 84 LAD patients from 33 centers, all receiving an allo-HSCT from 2007 to 2017. The 3-year overall survival estimate (95% confidence interval [CI]) was 83% (74-92) for the entire cohort: 84% (75-94) and 75% (50-100) for LAD-I and LAD-III, respectively. We observed cumulative incidences (95% CI) of graft failure (GF) at 3 years of 17% (9%-26%) and grade II to IV acute graft-versus-host disease (aGVHD) at 100 days of 24% (15%-34%). The estimate (95% CI) at 3 years for GF- and GVHD-II to IV-free survival as event-free survival (EFS) was 56% (46-69) for the entire cohort; 58% (46-72) and 56% (23-88) for LAD-I and LAD-III, respectively. Grade II to IV acute GVHD was a relevant risk factor for death (hazard ratio 3.6; 95% CI 1.4-9.1; P = .006). Patients' age at transplant >= 13 months, transplantation from a nonsibling donor, and any serological cytomegalovirus mismatch in donor-recipient pairs were significantly associated with severe acute GVHD and inferior EFS. The choice of busulfan- or treosulfan-based conditioning, type of GVHD prophylaxis, and serotherapy did not impact overall survival, EFS, or aGVHD. An intrinsic inflammatory component of LAD may contribute to inflammatory complications during allo-HSCT, thus providing the rationale for considering anti-inflammatory therapy pretreatment