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Double Unit Umbilical Cord Blood Transplant for Adults with Acute Leukemia and Myelodysplastic Syndrome Results in Comparable Outcome As Matched Sibling or Unrelated Donor Transplant Only after Myeloablative Conditioning but Not Reduced Intensity Conditio
The infusion of 2 partially HLA-matched umbilical cord blood (UCB) is a potential strategy for extending UCB transplantation to more patients. The risk and benefits of double UCB transplantation (dUCBT) relative to those observed after transplantation with related and unrelated adult donors remains to be determined.
Methods
Two hundred and eighty three adult patients undergoing first allogeneic transplant for acute myeloid leukemia (N=166), acute lymphocytic leukemia (N=87) and myelodysplastic syndrome (N=30) at Singapore General Hospital (N=176) and National University Cancer Institute, Singapore (N=107) between 2005-2013 were studied. The patients received transplantation using matched related donor (MRD, n=172), matched unrelated donor (MUD, n=70) or 4-6/6 HLA matched dUCB (n=41) graft after myeloablative conditioning (MAC, n=147) or reduced intensity conditioning (RIC, N=136), consisting of fludarabine, cyclophosphamide (120 mg/kg for MAC , 50 mg/kg for RIC) and total body irradiation (12-14 Gy for MAC, 2 Gy for RIC).
Results:
The leukemia free survival at 5 years was similar for each donor type, 43% for dUCB, 45% for MSD and 42% for MUD (p=0.26). There was no statistically significant difference in relapse-related death and transplant-related mortality among the 3 donor types. However, when the outcome was analyzed separately according to conditioning regimen, a significant difference in survival was observed among patients receiving RIC. As compared to the recipients of MSD or MUD, the risk of relapse-related death was highest in recipients of dUCB (HR 2.75, 95% CI 1.05-7.1; p=0.04) after RIC, resulting in the lowest overall survival (dUCB 9%; MSD 43%; MUD 29%; p=0.009). For patients receiving MAC, leukemia-free survival in patients after dUCBT (59%) was comparable to that after MSD (46%) and MUD (52%) transplantation (p=0.82)
Conclusions:
Our results support the use of 2 partially HLA-matched UCB as a suitable alternative for patients without an available HLA matched donor. However, the use of RIC for dUCBT is still limited by high incidence of relapse. Future studies are necessary to define the best regimen that can induce sustained engraftment without increasing the risk of relapse and regimen-related toxicity.