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Fludarabine/busulfan conditioning based allogeneic hematopoietic cell transplantation for myelofibrosis: Role of ruxolitinib in improving survival outcomes
Chhabra, S., Narra, R. K., Wu, R., Szabo, A., George, G., Michaelis, L. C., D'Souza, A., Dhakal, B., Drobyski, W. R., Fenske, T. S., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment modality for primary myelofibrosis (MF) and related myeloproliferative neoplasms. Older age at diagnosis and age-related comorbidities make most patients ineligible for alloHCT, given concerns for non-relapse mortality (NRM). Herein, we report the outcomes of 37 consecutive recipients of allogeneic HCT for MF performed at a single center between 2009 and 2018 with a standardized institutional protocol. Most patients received ruxolitinib prior to HCT (n=32), and those with splenomegaly >22 cm received pre-transplant splenic irradiation. Median age at HCT was 60 years (range, 40-74): 68% carried JAK2 driver mutation. All patients received fludarabine/busulfan-based conditioning: 22 patients (59%) received reduced intensity conditioning. All patients received peripheral blood grafts. Sixteen (43%) patients had matched sibling donor, and others had unrelated (n=20) or haploidentical-related donor (n=1). Sixty one percent had an HCT-CI score ≥3, 40% had KPS <90 and 24% had a high-risk DIPSS Plus score. With a median follow-up of 40.2 months (range, 16.9-115), the 3-year overall and relapse-free survival were 81.1% (95% Confidence Interval [95%CI], 64.4-90.5%) and 78.4% (95% CI, 61.4-88.5%), respectively. Only two patients relapsed/progressed after transplant. NRM at 2 years was 16.2% (95% CI, 6.5-29.9%). All patients engrafted. Sixteen patients were treated with ruxolitinib post-transplant for treatment of GVHD, graft rejection/relapse and persistent MF. These results suggest that pre-transplant ruxolitinib, fludarabine/busulfan-based conditioning and splenic management are keys to improved transplant outcomes in MF.