Reduced intensity allogeneic stem cell transplantation for younger patients with myelofibrosis

Abstract

Allogeneic stem cell transplantation (alloSCT) is a curative procedure for myelofibrosis. Elderly people are mainly affected, limiting the feasibility of myeloablative regimens. The introduction of reduced-intensity conditioning (RIC) made alloSCT feasible for older patients. Nevertheless, the incidence of myelofibrosis is not negligible in young patients, who are theoretically able to tolerate high-intensity therapy. Very few data are available about the efficacy of RIC-alloSCT in younger myelofibrosis patients. This study included 56 transplanted patients aged <55 years. Only 30% had a human leucocyte antigen (HLA)-matched sibling donor, the others were transplanted from a fully-matched (36%) or partially-matched (34%) unrelated donor. All transplants were conditioned according the European Society for Blood and Marrow Transplantation protocol: busulfan-fludarabine + antithymocyte globulin, followed by ciclosporin and mycophenolate. One patient experienced primary graft failure. Incidence of graft-versus-host disease grade II-IV was 44% (grade III/IV 23%). One-year non-relapse mortality was 7% and the 5-year cumulative incidence of relapse was 19%. After a median follow-up of 8Á6 years, the estimated 5-year progression-free survival and overall survival (OS) was 68% and 82%, respectively. Patients with fully-matched donor had a 5-year OS of 92%, in contrast to 68% for those with a mismatched donor (P = 0Á03). The most important outcomedetermining factor is donor HLA-matching. In conclusion, RIC-alloSCT ensures optimal engraftment and low relapse rate in younger myelofibrosis patients, enabling the possibility of cure in this group.

Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: A study of the chronic malignancies working party of EBMT and the Spanish Myelofibrosis Registry

“…Overall, 40% were alive at 5 years after transplantation, a lower figure than the 50% to 65% long‐term survival reported in recent series of allo‐HCT in all‐age MF patients 10,14,21–24 . Increased NRM (37% at 5 years), mostly attributed to GVHD, was the main cause of worse survival, as the relapse rate (25% at 5 years) was comparable to that reported in younger MF patients 10,14,22–26 . Busulfan‐based conditioning was associated with lower NRM and improved survival, whereas harboring the JAK2 mutation and the CMV‐negative donor to CMV‐positive recipient combination implied higher NRM and shorter overall survival.…”

“…Ratios higher than one imply greater mortality in the transplant group F I G U R E 4 Estimated survival according to sex in myelofibrosis patients aged 65 years or older managed with conventional drug treatment A, or allo-HCT B [Color figure can be viewed at wileyonlinelibrary.com] (25% at 5 years) was comparable to that reported in younger MF patients. 10,14,[22][23][24][25][26] Busulfan-based conditioning was associated with lower NRM and improved survival, whereas harboring the JAK2 mutation and the CMV-negative donor to CMV-positive recipient combination implied higher NRM and shorter overall survival. None of these factors had any influence on relapse risk.…”

“…10,14,[21][22][23][24] Increased NRM (37% at 5 years), mostly attributed to GVHD, was the main cause of worse survival, as the relapse rate (25% at 5 years) was comparable to that reported in younger MF patients. 10,14,[22][23][24][25][26] Busulfan-based conditioning was associated with lower NRM and improved survival, whereas harboring the JAK2 mutation and the CMV-negative donor to CMV-positive recipient combination implied higher NRM and shorter overall survival. None of these factors had any influence on relapse risk.…”

Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis

“…Further prospective randomized trials are needed to better evaluate optimal conditioning intensity, however, there is evidence that RIC may be as effective with less toxicity even among young, MSD recipients. 80 In the last two decades, RIC has been used in around two‐thirds of patients in European centers, although this is confounded by increasing age at transplant (median 49.4 vs. 59.3 years). 81 Comparison between the two commonly used regimens, consisting of fludarabine with either busulfan or melphalan, shows similar OS outcomes.…”

“…The authors concluded that MAC remained the preferred conditioning in the remaining population. Further prospective randomized trials are needed to better evaluate optimal conditioning intensity, however, there is evidence that RIC may be as effective with less toxicity even among young, MSD recipients 80 . In the last two decades, RIC has been used in around two‐thirds of patients in European centers, although this is confounded by increasing age at transplant (median 49.4 vs. 59.3 years) 81 .…”