Clofarabine Containing Conditioning Regimen for Allo-SCT in AML/ALL Patients: A Survey From the Acute Leukemia Working Party of EBMT

Abstract 3004^FN2

Clofarabine (CLO), a second generation purine analogue, has demonstrated an efficient anti-leukemia activity while showing a favorable toxicity profile. The aim of our study was to analyse the results of CLO as part of the conditioning regimen prior to allo-SCT for the treatment of patients with AML or ALL. This retrospective multicenter report assessed the outcome of 90 patients who received a clofarabine-containing conditioning regimen allogeneic stem cell transplantation (allo-SCT) for AML (n=69) or ALL (n=21) between November 2006 and September 2010 and reported on the EBMT registry. The median age was 42 years (range: 18–69) at transplant. The majority of patients presented with an active disease at transplant (CR1 n=8; CR2 n=16, active disease n=66). All patients had received a CLO-containing conditioning regimen (RIC n=88; MAC n=2) with the following combinations: CLO/TBI n=27; CLO/Busulfan n=10; CLO/Busulfan/ATG n=32; CLO/others drugs n=21. With a median follow-up of 14 months (range: 1–45), 2-years OS, LFS, relapse incidence, non-relapse mortality (NRM) and chronic GVHD were 28+-5%, 23+-5%, 41+-6%, 35+-5% and 38+-7%, respectively. When comparing AML and ALL patients, OS and LFS were significantly higher for AML patients (OS: 35+-6% vs 0%, p<0.0001); LFS: 30+-6% vs 0%, p<0.0001). Overall, engraftment was achieved in 84% of patients with no difference between AML and ALL patients. Patients achieving CR from an active disease were 66.5% in AML vs 40% in ALL (p=0.06). Also, 2-year chronic GVHD was 35% in AML vs 17% in ALL, p=0.32. In a Cox multivariate analysis, AML was the only factor associated with a better LFS (HR=0.37; 95%CI: 0.21–0.66, P=0.001). We conclude that the use of CLO-containing conditioning regimen for allo-SCT is an effective treatment for high-risk AML patients as CLO seems to provide higher anti-tumor and alloreactivity effects. In high-risk ALL patients, disappointing results are observed. Prospective studies are needed to evaluate the potential role of CLO as part of reduced toxicity conditioning regimens in acute leukemias.