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Fludarabine/Busulfan Conditioning-Based Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis: Role of Ruxolitinib in Improving Survival Outcomes. Biol Blood Marrow Transplant 2020 May;26(5):893-901

Date

01/27/2020

Pubmed ID

31982543

DOI

10.1016/j.bbmt.2020.01.010

Scopus ID

2-s2.0-85080146585   3 Citations

Abstract

Allogeneic hematopoietic cell transplantation (allo-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 allo-HCT, given concerns for nonrelapse mortality (NRM). Here we report the outcomes of 37 consecutive recipients of allo-HCT for MF performed at a single center between 2009 and 2018 with a standardized institutional protocol. Most patients received ruxolitinib before HCT (n = 32), and those with splenomegaly >22 cm received pretransplantation splenic irradiation. The median age at HCT was 60 years (range, 40 to 74 years), and 68% of the cohort carried a JAK2 driver mutation. All patients received fludarabine/busulfan-based conditioning; 22 patients (59%) received a reduced-intensity conditioning regimen. All patients received peripheral blood grafts, from a matched sibling donor in 16 patients (43%), an unrelated donor in 20 patients, and a haploidentical-related donor in 1 patient. Sixty-one percent had a Hematopoietic Cell Transplantation Comorbidity Index ≥3, 40% had a Karnofsky Performance Status score <90, and 24% had a high-risk DIPSS Plus score. With a median follow-up of 40.2 months (range, 16.9 to 115 months), the 3-year overall survival and relapse-free survival were 81.1% (95% confidence interval [CI], 64.4% to 90.5%) and 78.4% (95% CI, 61.4% to 88.5%), respectively. Only 2 patients relapsed/progressed after transplant. NRM at 2 years was 16.2% (95% CI, 6.5% to 29.9%). All patients engrafted. Sixteen patients were treated with ruxolitinib post-transplantation for graft-versus-host disease, graft rejection/relapse, or persistent MF. These results suggest that pretransplantation ruxolitinib, fludarabine/busulfan-based conditioning, and splenic management are keys to improved transplantation outcomes in patients undergoing allo-HCT for MF.

Author List

Chhabra S, Narra RK, Wu R, Szabo A, George G, Michaelis LC, D'Souza A, Dhakal B, Drobyski WR, Fenske TS, Jerkins JH, Pasquini MC, Rizzo RD, Saber W, Shah NN, Shaw BE, Hamadani M, Hari PN

Authors

Saurabh Chhabra MD Associate Professor in the Medicine department at Medical College of Wisconsin
Anita D'Souza MD Associate Professor in the Medicine department at Medical College of Wisconsin
Binod Dhakal MD Associate Professor in the Medicine department at Medical College of Wisconsin
William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin
James H. Jerkins MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
Wael Saber MD, MS Associate Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Associate Professor in the Medicine department at Medical College of Wisconsin
Bronwen E. Shaw MBChB, PhD Professor in the Medicine department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin




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