17: Double Reduced Intensity Cord Blood Transplants in Adults

Abstract

Umbilical cord blood is a useful stem cell source for patients without matched donors, but the low cell dose in individual cord blood units has limited success in adults. We treated 43 patients using a reduced intensity conditioning regimen of fludarabine 30 mg/m2/day Days –8 through –3 (total dose 180 mg/m2), melphalan 100 mg/m2 Day –2 and rabbit antithymocyte globulin 1.5 mg/kg Days –7, −5, −3, −1 (total dose 6 mg/kg). Cord blood units were a 4/6 or higher HLA A, B, DR allele match with the patient and each other and achieved a minimum precryopreservation cell dose of 3.7 × 10 (7) NC/kg. Twenty-one patients received GVHD prophylaxis with cyclosporine and mycophenolate mofetil and 22 patients received tacrolimus and sirolimus. Median age was 49 years and majority of patients had acute leukemia or relapsed lymphoma. The median days to neutrophil and platelet engraftment were 20 and 41 days respectively for the cyclosporine/MMF group and 21 days and 47 days for the tacrolimus/sirolimus patients. The incidence of acute GVHD Grades II-IV and chronic GVHD in the cyclosporine/MMF group was 40% and 34% respectively and 14% and 20% respectively for the tacrolimus/sirolimus patients. Transplant related mortality was 14% in both groups. Overall survival and disease free survival were 57% and 57% at 2 years respectively for the cyclosporine/MMF patients and 73% and 51% at one year for the tacrolimus/sirolimus patients. In a multivariate analysis, age greater than 50 was the only significant predictor of poorer survival. Chimerism studies revealed that one cord unit predominates in 73% of patients. Predictors of the predominant unit include first infusion and higher CD34 and nucleated cell counts. Double cord blood transplantation can be performed safely with this reduced intensity regimen; the graft vs leukemia effect is preserved despite a low rate of graft versus host disease.