Long-Term Survival of Patients with Relapsed/Refractory Acute Leukemia Receiving Clofarabine/Cyclophosphamide Prior to Hematopoietic Stem Cell Transplantation

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative option for patients with drug-refractory acute myeloid (AML) or acute lymphoblastic leukemia (ALL). Patients and Methods: We retrospectively analyzed 82 patients (median age 47.5 years, range 19–69; female:male ratio 1:1.28) with drug-refractory (R) or relapsed/refractory (RR) acute leukemia (AML n = 66; ALL n = 16) who were treated with clofarabine (10 mg/m2) and cyclophosphamide (200 mg/m2) days 1–4 (ClofCy) prior to HSCT. Results: ClofCy resulted in rapid cytoreduction (median time to granulocytes <0.5 × 109/L: 5 days). HSCT was performed in 62.2% (51/82) of our patients. Infections (18/31, 58%) were the main reason to withhold transplantation. HSCT and non-HSCT patients differed significantly regarding the median number of chemotherapies received prior to ClofCy (HSCT, median = two therapies; non-HSCT, median = three therapies; p = 0.027). Median overall survival (OS) was 0.31 years in all patients (5- and 10-year OS; 24% and 20%, respectively). HSCT patients had a median OS of 1.23 years (5- and 10-year OS; 38.4% and 31%, respectively) and those in the non-HSCT cohort a median OS of 0.11 years (5-year OS; 0%). Median OS and relapse-free survival (RFS) in the HSCT patient cohort were 1.04 and 0.9 years, respectively. Acute graft-versus-host disease (aGvHD) was associated with inferior survival (median OS 0.46 years), whereas chronic graft-versus-host disease (cGvHD) was associated with improved OS and RFS (above 50%). Conclusion: ClofCy is an effective bridging regimen enabling HSCT in patients with R/RR acute leukemia. Introducing ClofCy may improve the probability of reaching HSCT and long-term survival in this cohort of patients with poor prognosis.