Introduction: Outcomes for patients (pts) with acute myelogenous leukemia (AML) who undergo allogeneic stem cell transplant (SCT) with active disease are dismal, especially with reduced intensity conditioning regimens. Novel approaches to transplant are needed to improve outcomes in this high risk, often-elderly patient population. The Clofarabine Busulfan 4 (Clo/Bu4) conditioning regimen has been described in a small number of pts as a well-tolerated and promising regimen that resulted in higher than anticipated long term remissions (Magenau, 2011). We report our experience using Clo/Bu4 for pts undergoing related and matched unrelated (MUD) allogeneic SCT with relapsed and refractory AML.

Methods: From 2010-2013,16 patients aged >18 years received an allogeneic SCT from a matched sibling or unrelated donor for active AML using Clo/Bu4. After IRB approval, we compared outcomes in this cohort with 16 historical controls undergoing transplant with active AML receiving institutional standard conditioning regimens (Cytoxan/Total Body Irradiation (Cy/TBI) or Fludarabine/Busulfan (Flu/Bu). Case and control pts are compared for overall survival (OS) and relapse-free survival (RFS) using Kaplan-Meier estimation and the log-rank statistics. For the Clo/Bu4 cohort, we also describe GVHD and time to engraftment, (the first of 3 consecutive days with ANC >500).

Results: Sixteen pts were conditioned with Clo/Bu4 prior to allo SCTand 16 received conventional regimens (14 Cy/TBI and 2 Flu/Bu). Both groups had a median of 3 prior therapies, (Clo/Bu4 range 2-6, control group 2-5). In both groups, 8/16 pts (50%) received grafts from an unrelated donor (URD). In the Clo/Bu4 group, 4 had HLA mismatched URD grafts while 2 pts in the control group received single antigen mismatched grafts (1 URD and 1 sib). Overall, pts in the Clo/Bu4 cohort appeared to be at higher risk; pts were older (median 59.2 vs 51.4 years), had a higher percentage of blasts in their pre-transplant bone marrow (40% vs 18%), and had a higher average HCTCI comorbidity score (4.5 vs. 2.8) vs the control group. RFS at 1 year for the Clo/Bu4 and control pts was 79% and 19%, respectively (P=.0035). OS in the Clo/Bu4 and control groups is 81% and 25%, respectively (P=.0078) (Figure 1).

Of the 16 Clo/Bu4 pts, 14 (88%) engrafted within 30 days. Pts received tacrolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis. Eight Clo/Bu4 pts (50%) had acute GVHD grade I/II and 2 (12.5%) had grade III/IV acute GVHD. In 8/16 (50%) Clo/Bu4 pts there was mild/moderate chronic GVHD of at least one organ, and only 2 of these pts had severe symptoms.

Conclusion: Pts with active AML/MDS who undergo allogeneic SCT with Clo/Bu4 conditioning have improved RFS and OS when compared to similar pts who receive more conventional Cy/TBI or Flu/Bu conditioning regimens. While more than half of the patients experienced some level of GVHD, most cases remained mild to moderate in both acute and chronic presentations. Our data supports the use of this regimen for pts with relapsed and refractory disease, even in elderly pts and those with mismatched donors.


Mangan:Alexion Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Gill:Novartis: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.