Reduced-Intensity Hematopoietic Cell Transplantation for Patients with Primary Myelofibrosis: A Cohort Analysis from the Center for International Blood and Marrow Transplant Research

Abstract

We evaluated the outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced intensity conditioning (RIC). Median age at HCT was 55 years. Donors were: matched sibling donor (MSD), 34%; HLA-well-matched unrelated donors (URD), 45%; and partially/mismatched URD, 21%. Risk stratification according to Dynamic International Prognostic Scoring System (DIPSS): low, 12%; intermediate-1, 49%; intermediate-2, 37%; and high, 1%. The probability of survival at 5-years was 47% (95% CI 40–53). In a multivariate analysis, donor type was the only independent factor associated with survival. Adjusted probabilities of survival at 5-years for MSD, well matched URD and partially matched/mismatched URD were 56% (95% CI 44–67), 48% (95% CI 37–58), and 34% (95% CI 21–47), respectively (p=0.002). Relative risks (RR) for NRM for well-matched URD and partially matched/mismatched URD were 3.92 (p=0.006) and 9.37 (p<0.0001), respectively. A trend towards increased NRM (RR 1.7, p=0.07) and inferior survival (RR 1.37, p=0.10) was observed in DIPSS-intermediate-2/high-risk patients compared to DIPSS-low/intermediate-1 risk patients. RIC HCT is a potentially curative option for patients with MF, and donor type is the most important factor influencing survival in these patients.

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

“…20 Since the study excluded patients with PPV-MF, PET-MF and those who had transformed to AML, it offers an assessment of the role of RIC allo-SCT in PMF, using a validated risk-assessment tool (DIPSS) which addresses the course of disease. The study cohort DIPSS-risk stratification was low (12%), intermediate-1 (49%), intermediate-2 (37%), high (1%) and unknown (1%).…”

“…RIC is associated with a lower NRM, but a higher risk of relapse, compared with standard myeloablative conditioning, and the current results suggest a qualified success (Table 1). [17][18][19][20][21] The notion of using ruxolitinib in order to reduce constitutional symptoms and splenomegaly prior to allo-SCT appears attractive. What is not known is the drug's impact on short-and long-term outcomes following allo-SCT; nor is the precise timing of allo-SCT or the role of allo-SCT-specific prognostic and predictive scores in the JAK-inhibitor era known.…”

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

“…[2][3][4][5][6][7][8][9] The introduction of non-myeloablative-(NMA) and reduced-intensity conditioning (RIC) 10 regimens resulted in a lower TRM/non-relapse mortality rate of 16-30% at 1-5 years, with similar OS rates (31-67% after 3-5 years). 2,6,9,[11][12][13] However, randomized prospective data comparing myeloablative with RIC/NMA conditioning are lacking.…”

“…Therefore, data considering the superiority of one regimen over the other are still lacking. 11 Here we report a retrospective analysis of 53 patients who were transplanted for myelofibrosis in three transplantation centers in the Netherlands, with an emphasis on conditioning regimens and engraftment outcome.…”

Allogeneic hematopoietic stem cell transplantation for myelofibrosis and chronic myelomonocytic leukemia

“…Of the various scoring systems, only the DIPSS has proven to predict OS consistently after HSCT. [8][9][10][11][12] There have been other attempts to more specifically determine the prognosis of patients undergoing HSCT for PMF, but these efforts have generally been difficult because HSCT cohorts are small, retrospective and fraught with selection bias. Factors identified to correlate with worse OS after HSCT for MF include number of prior red blood cell transfusions, massive splenomegaly, unrelated or mismatched donor, JAK2V617F mutation status, recipient age and constitutional symptoms.…”