Superior Survival After Single Unit Umbilical Cord Blood Transplantation (UCBT) in Children with Hematological Malignancies Treated On Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0501 Relative to the Cord Blood Transplantation (COBLT)

We compared overall survival for recipients of a single UCB unit treated for hematological malignancy on the COBLT Study (n=191) conducted from 1999-2004 to BMT CTN 0501 (n=113) conducted from 2006-2012.  The BMT CTN 0501 is sponsored by NHLBI and NCI and, COBLT was sponsored by NHLBI.  Overall survival at 1-year was the primary endpoint for both trials.  Eligibility for both trials was similar with a minimum total nucleated cell dose (TNC) of 2.5x10⁷/kg for BMT CTN and 1x10⁷/kg for COBLT and HLA match of 4/6 at antigen level for HLA A and B and allele level for HLA DRB1.  All patients received TBI 1350 cGy and cyclophosphamide 120 mg/kg.  Patients enrolled on COBLT also received equine ATG 90 mg/kg and those on BMT CTN 0501 fludarabine 75mg/m² with GVHD prophylaxis consisting of cyclosporine/methyl prednisone and cyclosporine/mycophenolate mofetil, respectively. The distribution of patient performance scores, diseases, TNC (median dose: 4.8 x 10⁷/kg for BMT CTN 0501 and COBLT, 5. 1 x 10⁷/kg) and CD34 dose of the UCB units were similar. Compared to those on BMT CTN 0501, patients on COBLT were slightly younger (median age: 8 vs. 10 years, p=0.0007), more likely to be in relapse at transplant (16% vs. 5%, p=0.0002) and less likely to receive a 5-6/6 HLA-matched unit (29% vs. 59%, p<0.0001).  The 1-year, the probabilities of overall survival were 57% (95% CI 50 – 64) on COBLT and 71% (95% CI 62 – 79) on BMT CTN 0501 (p=0.01).  In multivariate analysis, mortality risks were higher for patients enrolled on COBLT compared to those on BMT CTN 0501 (HR 1.82, 95% CI 1.19 – 2.78, p=0.006).  Mortality risks were also higher in non-Caucasians independent of clinical trial (HR 1.95, 95% 1.32 – 2.88, p=0.0007).  The primary causes of death on both trials were similar except for higher incidence of primary graft failure on COBLT.  The most frequent causes of death in both treatment groups were recurrent leukemia and GVHD.  In summary, survival was better for patients treated on BMT CTN 0501.  Although it is not possible to prove which factor(s) played the greatest role, it is the “package” including conditioning and GVHD prophylactic regimens, supportive care, method of unit selection and transplantation period combined that contributed to the improved survival observed in recipients of a single UCB unit in BMT CTN 0501.  Together, these results suggest the BMT CTN 0501 treatment plan represents the new standard by which treatment modifications will be compared.