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Clinical Trial
. 2017 Jan;52(1):59-65.
doi: 10.1038/bmt.2016.188. Epub 2016 Jul 18.

A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation

J Magenau  1 , P Westervelt  2 , S Khaled  3   4 , J McGuirk  4 , P Hari  5 , M Eapen  5 , P S Becker  6 , B Parkin  1 , T Braun  7 , B Logan  8 , H Wang  8 , M Jagasia  9 , S D Rowley  10 , D D H Kim  11 , T Schechter  12 , N Frey  13 , B Scott  6 , T Churay  1 , S Lieland  1 , S Forman  3   4 , S Mineishi  14
Affiliations
Clinical Trial

A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation

J Magenau et al. Bone Marrow Transplant. 2017 Jan.

Abstract

Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission. Seventy-one patients (median age: 56 years) received CloBu4. At day 30 after HCT, 90% achieved morphologic remission. The incidence of non-relapse mortality and relapse at 2 years was 25% and 55%, respectively. The 2-year overall survival (OS) and event-free survival (EFS) were 26% and 20%, respectively. Patients entering HCT in PIF had significantly greater EFS than those in relapse (34% vs 8%; P<0.01). Multivariate analysis comparing CloBu4 with a contemporaneous cohort (Center for International Blood and Marrow Transplantation Research) of AML not in remission receiving other myeloablative conditioning (n=105) demonstrated similar OS (HR: 1.33, 95% confidence interval: 0.92-1.92; P=0.12). HCT with myeloablative CloBu4 is associated with high early response rates and may produce durable remissions in select patients with AML not in remission.

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Figures

Figure 1
Figure 1
(a) Cumulative incidence of relapse or progression of AML following HCT, (b) Cumulative incidence of TRM for AML not in remission at HCT receiving CloBu4 conditioning.
Figure 2
Figure 2
(a) Overall survival, (b) Event-free survival for AML not in remission at HCT receiving CloBu4 conditioning.
Figure 3
Figure 3
Non-remission AML after PIF (solid line), defined as no remission after ≥ 2 lines of induction or non-remission AML after relapse (hatched line).
See this image and copyright information in PMC

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