Family Mismatched Allogeneic Stem Cell Transplantation for Myelofibrosis: Report from the Chronic Malignancies Working Party of European Society for Blood and Marrow Transplantation

Abstract

This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57 years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34 + cell dose was 4.8 £ 10 6 /kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28 days was 82% (range, 70% to 93%), at a median of 21 days (range, 19 to 23). At 2 years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100 days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1-and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1-and 2-year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19%

Reduced‐intensity conditioning allogeneic transplant with dual T‐cell depletion in myelofibrosis

“…The use of mismatched unrelated donor allo-HSCT in MF has been associated with worse post-transplant outcomes and higher NRM. 39 However, the use of alternative donor sources should be considered in the absence of a suitable match donor. The present protocol was reviewed, and the dose or ATG was reduced to 2 mg/kg.…”

“…The molecular and cytogenetic profile at diagnosis should be considered in order to better determine the optimal timing for transplant and post-transplant outcome. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] MIPSS70+ v2.0 should be assessed prior to allo-HSCT because it has been found to be predictive for long-term survival in MF patients after allo-HSCT. 32 In conclusion, the use of RIC allo-HSCT combined with ATG and PTCy results in promising 1-year OS and RFS in patients with MF mainly using MRD and 10/10 MUD grafts.…”

Allogeneic hematopoietic stem-cell transplantation for myelofibrosis

“…With a median follow up of 32 months, the 2-year OS, PFS and NRM was 56%, 43%, 38%, respectively. 70 It was the largest study of patients with MF undergoing MMRD AHSCT. The acceptable levels of GVHD and encouraging PFS and OS rates demonstrated its feasibility.…”

Selecting patients with primary myelofibrosis for stem cell transplant using clinical, mutational, and transplant‐specific profiles

“…No comparative studies on the outcomes of matched unrelated donor and haploidentical donors in PMF have been published to date. Only 1 retrospective study from the European Society for Blood and Marrow Transplantation (EBMT) demonstrated feasibility of the haploidentical approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression‐free survival rates with relapse rates not dissimilar to the unrelated donor setting . However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality of 38% at 2 years need to be evaluated.…”