Clofarabine for Cytoreduction Prior to Allogeneic Transplant Conditioning for Refractory Acute Myelogenous Leukemia

Abstract 4506

The treatment of primary refractory and relapsed refractory acute myelogenous leukemia (AML) is unclear. We report on a retrospective analysis of all patients who received clofarabine for refractory AML immediately prior to allogeneic hematopoietic stem cell transplantation between 2006 and 2011. Eleven patients with refractory AML received clofarabine 40 mg/m² with or without cytarabine 100mg/m² prior to allogeneic transplantation. Nine patients had primary refractory disease and two were in first relapse. The median age was 62 (24–66) with 6 men and 5 women. Three patients had de novo AML, seven had prior MDS and one had prior polycythemia vera. One patient had undergone a prior autologous stem cell transplant. Cytoreduction with less than 10% blasts in the marrow was achieved in forty-four percent of patients. Two patients died prior to time of transplant due to infectious complications. At the time of transplant, six of the patients (66%) had infectious complications at time of transplantation. Three of the patients (33%) had documented bacteremia prior to transplant. Of the nine patients who proceeded to allogeneic transplantation, six received reduced-intensity conditioning (RIC) consisting of extracorporeal photopheresis for two days, Pentostatin 4mg/m² × 2 days and 600 cGy fractionated TBI. Three patients received myeloablative conditioning with two patients receiving Cytoxan/TBI 1200 cGy and one patient receiving Busulfan/Cytoxan. Grade I-II hyperbilirubinemia and Grade I-II transaminitis were documented in four patients (44%) and five patients (55%) of patients after clofarabine administration prior to transplant, respectively. Grade I acute GvHD occurred in five patients (55%) and grade II acute GvHD was present in two patients (22%). No patient developed Grade III or IV acute GvHD. The 100 day transplant-related mortality was 1/3 (33%) and 4/6 (66%) in the RIC group and in the myeloablative conditioning group, respectively. One patient died of sinusoidal obstruction syndrome on day 20. The 100 day overall survival in patients who did not achieve effective cytoreduction was comparable to those with effective cytoreduction at 60% and 50%, respectively. The one year overall survival was 22%. One patient is alive and disease-free with out GVHD at 57 months.

Our findings demonstrate that survival at 100 days and one year was independent of clofarabine cytoreduction. These results suggest that effective cytoreduction with clofarabine is not necessary for a prolonged response in patients with refractory AML. The one-year overall survival in this heavily pretreated refractory patient population is comparable to published data. Treatment related mortality was high, particularly in those patients who received a myeloablative conditioning which is attributable to infectious complications. However, the use of clofarabine followed by a RIC allogeneic transplant was tolerated and may be associated with a prolonged response.