MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis

Abstract

Key Points• A high survival rate was seen in primary or secondary MF patients transplanted from matched related donors using the FluMel regimen.• FluMel plus ATG in HSCT from unrelated donors for MF patients is associated with an increased risk of graft failure.From 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n 5 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n 5 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar. Engraftment occurred in 97% of siblings and 76% of unrelated transplants, whereas secondary graft failure occurred in 3% and 12%, respectively. With a median follow-up of 25 months for patients alive, the overall survival (OS) was 75% in the sibling group (median not reached) and 32% in the unrelated group (median OS: 6 months, 95% confidence interval [CI]: 3, 25) (hazard ratio 3.9, 95% CI: 1.8,8.9) (P < .001). Nonrelapse mortality was 22% in sibling and 59% in unrelated AHSCT. Survival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2 V617F status. In patients with MF with sibling donors, AHSCT is an effective therapy, whereas AHSCT from unrelated donors with FluMel/ATG conditioning led to a high rate of graft failure and limited survival. This trial was registered at www.clinicaltrials.gov as

Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

“…Lille IPSS DIPSS DIPSS plus 95 The study cohort comprised all MF subtypes and included~35% intermediate-2/high-risk DIPSS. Following a median follow-up of 25 months, 24 of 32 patients who had received a related allograft (30 matched; 2 mismatched) following Flu-Mel conditioning, were alive compared to 11 of 34 who had received an unrelated allograft (25 matched; 9 mismatched) following Flu-Mel-ATG conditioning.…”

Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis

“…[5][6][7]12,[14][15][16] Data on graft failure are not uniform and no definitive predictors for graft failure have yet been determined, but factors that have been associated with unsuccessful engraftment include: transplantation from an alternative donor (a (mis)matched unrelated donor, cord blood donor or haploidentical sources), inadequate numbers of CD34+ cells infused, degree of splenomegaly, selection of GvHD prophylaxis, degree of fibrosis with osteosclerosis and thrombocytopenia pre-transplantation. 2,8,[14][15][16][17] Moreover, the type of conditioning (RIC versus NMA or myeloablative) might affect the occurrence of graft failure. In a retrospective analysis, Gupta et al did recently describe a trend toward superior survival in patients who received fludarabine/ melphalan compared with those who received fludarabine/ busulfan or TBI/fludarabine.…”

Splenic pooling and loss of VCAM-1 causes an engraftment defect in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation

“…Our data indicate that MF patients show significantly delayed early and late neutrophil, as well as late platelet engraftment, compared to the AML cohort. Analysis of engraftment-related factors Engraftment defect in patients with myelofibrosis haematologica | 2016; 101 (11) 1413 8 and Rondelli et al 19 reported a significant difference in engraftment between MRD and MUD. This divergence might be due to the somewhat smaller number of patients within our study.…”