Allogeneic transplantation for myelofibrosis: Final analysis of a prospective study after a median follow up of 5 years.

Leukemia, Myelodysplasia, and Transplantation
Session Type and Session Title: 
Oral Abstract Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 7008)
Uday R. Popat, Roland L. Bassett, Julianne Chen, Amin Majid Alousi, Paolo Anderlini, Stefan O. Ciurea, Chitra Hosing, Roy B. Jones, Partow Kebriaei, Issa F. Khouri, Sergej Konoplev, Marcos J.G. De Lima, Yago Nieto, Betul Oran, Muzaffar H. Qazilbash, Gabriela Rondon, Elizabeth J. Shpall, Srdan Verstovsek, Borje Andersson, Richard E. Champlin; The University of Texas MD Anderson Cancer Center, Houston, TX

Abstract Disclosures


Background: We report final results of a prospective phase II clinical trial of busulfan(bu) and fludarabine(flu) conditioning in patients with myelofibrosis(MF). After observing a higher relapse rate in the initial cohort, we increased the intensity of conditioning regimen for subsequent patients. Here we report updated mature results with a median follow up of 5 years. Methods: Patients with advanced MF were eligible if they had adequate organ function and at least 9/10 HLA matched related or unrelated donor. Of the 46 patients, first 15 (bu low group) received IV busulfan 130 mg/m2/day x 2 (day -3,-2). Of the remaining 31 (bu high group), 27 received IV busulfan dose to a target daily AUC of 4000 μmol.min x 4 (day -5 to -2) and 4 patients received a fixed dose of 100 mg/m2/day x 4 (days -5 to -2). All patients received fludarabine 40mg/m2x 4 (day -5 to -2). Results: 23 males and 23 females with a median age of 58 years (27-74) had intermediate (28) or high-risk (18) disease as per DIPSS plus criteria. Donors were matched sibs (19), matched unrelated (23), or mismatched unrelated (4). All patients engrafted with a median time to neutrophil engraftment of 13 (0-27) days and a median time to platelet engraftment of 24 (0-268) days. Cumulative incidence (CI) of grade II-IV, grade III, IV acute GVHD, and Chronic GVHD w 22%, 7%, and 40%, respectively. With a median follow up of surviving patients of 5.1 years (range 1-8.3 years), 3 year overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of non-relapse mortality (NRM), and CI of relapse were 69%, 48%, 13%, and 39%, respectively. Multivariate analysis showed that Bu-high dose (HR 0.44; p = 0.07) was associated with lower relapse rate. Bu-high dose (HR 0.5; p = 0.09), DIPSS plus high (HR 2.69; P = 0.02) and Age (HR 1.05; P = 0.08) were predictors of EFS. DIPSS plus high (HR 5.99; P = 0.001) and Age (HR 1.07; P = 0.03) were adverse predictors of OS. Conclusions: Allogeneic transplantation results in long-term survival in patients with myelofibrosis with better outcome seen in earlier phase of the disease. PK guided myeloablative busulfan (AUC 16,000 μmol.min) appears promising in reducing relapse rate without increasing non-relapse mortality.