Clofarabine and Busulfan Conditioning Facilitates Engraftment and Provides Significant Anti-Tumor Activity in Non-Remission Hematologic Malignancies Running Title: CloBu4 conditioning for HSCT

hematopoietic stem cell transplantation (HSCT) have a poor prognosis. To improve the anti-tumor activity of conditioning, we combined clofarabine (Clo) with myeloablative doses of busulfan (Bu) (CloBu4) in a phase I/II study in non - remission hematologic malignancies. Forty-six patients were enrolled including 31 patients with non-remission acute myelogenous leukemia (AML). Patients had a median age of 53 years with a median co-morbidity index of 3. Donors were unrelated and / or HLA mismatched in 59% of patients. Common grade 3-4 non-hematological toxicities included transient transaminitis (50%), mucositis (24%), hand-foot syndrome (13%), transient hypoxia (13%), nausea/vomiting (9%), and diarrhea (9%). All patients engrafted. Complete remission (CR) was achieved in 80% of all patients by day + 30 and in 100% of AML patients without prior HSCT. Two year non-relapse mortality for all patients was 31% and overall survival (OS) was 28%. In AML, the OS was 48% at 1 year and 35% at 2 years. These data suggest that clofarabine combined with myeloablative doses of busulfan is well tolerated, secures engraftment and possesses significant anti-tumor activity, particularly in non-remission AML. This study is registered at www.ClinicalTrials.gov under identifier NCT00556452.