Comparison of Single Versus Multiple Unit Umbilical Cord Blood Transplantation for Adult Hematologic Malignancy Patients

Abstract 3545

Umbilical cord blood transplantation (UCBT) is an alternative donor transplant approach for adult hematologic malignancy patients. Although UCBT was initially performed using single cord blood units (SCBU), a major limitation of this approach has been the low infused total nucleated cell (TNC) and CD34+ cell doses at the time of transplant. This accounts for delayed hematopoietic recovery post-transplant that increases the risk for infections and transplant-related mortality (TRM). Multiple unit (MU) UCBT has become an acceptable approach to increase the cell doses available for transplantation. We retrospectively compared outcomes for 38 consecutively treated adult hematologic malignancy patients who underwent SCBU (n=6) or MU (n=32) UCBT at our institution from October 1999 through April 2010. The median age was 49 years (range, 18–71) and 20 (53%) were men. Diagnoses included: 21 AML, 5 CML, 3 MDS, 5 ALL, 2 CLL, 1 NHL and 1 myelofibrosis. The majority of patients received myeloablative conditioning (n=32) most commonly with total body irradiation, etoposide and ATG (Sobecks et al, Br J Haematol 2010, in press) while those treated with reduced-intensity conditioning received fludarabine 40 mg/m2/day × 5 (days -6 through -2), cyclophosphamide 50 mg/kg (day -6), ATG 30 mg/kg/day × 5 (days -3 through +1) and total body irradiation 200 cGy (days -1 and 0; total dose 400 cGy). GVHD prophylaxis included a calcineurin inhibitor for all patients and most MU patients received mycophenolate mofetil. Among the SCBU group there were three 4/6 and three 5/6 HLA matches with the patient. For the MU group when considering the best matched UCB unit with the patient there were seven 4/6, nineteen 5/6 and six 6/6 HLA matches while for the worst matched UCB unit there were one 3/6, eleven 4/6, sixteen 5/6 and four 6/6 HLA matches with the patient. The SCBU group included more women than the MU group (100% vs. 38%, p<0.001). When comparing both groups there were no differences regarding age at transplant, race, CIBMTR comorbidity index score, median number of prior chemotherapy regimens, myeloid vs. lymphoid diagnosis, myeloablative vs. reduced-intensity conditioning, use of ATG, median TNC and CD34+ cell doses infused, time for neutrophil and platelet engraftment, graft failure or length of transplant hospitalization. However, as compared to the MU group the SCBU group had more grade 3–4 acute GVHD (HR 11.4, 95% CI 2.07–62.6, p=0.005) and a trend for more grade 2–4 acute GVHD (HR 2.80, 95% CI 0.85–9.22, p=0.09). There were no differences between the groups regarding the number of HLA disparities with the recipient when considering the worst matched, best matched or engrafting UCB unit. There also was no difference between the groups with regards to chronic GVHD. CMV infection developed in 2 (33%) SCBU patients and in 8 (25%) MU patients while other infections occurred in 5 (83%) SCBU patients and 30 (94%) MU patients. There has been 1 (17%) relapse in the SCBU group (ALL patient) and 3 (9%) in the MU group (1 MDS, 1 AML and 1 CML). One (17%) SCBU and 14 (44%) MU patients remain alive at a median follow-up of 15 months (range, 3–92 months). Deaths in the SCBU group included 2 acute GVHD, 2 disease relapses and 1 hemorrhage while in the MU group there were 10 infections, 2 pulmonary toxicities, 1 acute GVHD, 1 relapse, 1 hemorrhage, 1 graft failure, 1 multi-organ failure and 1 secondary malignancy. The respective 100 day mortality was 50% vs. 42%; 1 and 2 year transplant-related mortality 50% vs. 46% and 50% vs. 57%; 1 and 2 year relapse-related mortality were both 33% vs. 3% for the SCBU and MU groups. The greater amount of grade 3–4 acute GVHD in the SCBU patients could not be attributed to HLA disparities, conditioning regimen intensity, use of ATG, infused TNC or CD34+ cell doses. Further follow-up with more patients is required to confirm this finding and to adequately assess for a survival benefit between the groups. Novel approaches to enhance immune reconstitution and prevent infection after UCBT are warranted.