Multiple Unit HLA-Unmatched Sex-Mismatched Umbilical Cord Blood Transplantation for Advanced Hematological Malignancy

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Abstract
We investigated the effect of multiple-unit umbilical cord blood (UCB) transplantation on engraftment in the setting of severe human leukocyte antigen (HLA) mismatch. Ten poor-risk adult patients with hematological malignancy received multiple unit, HLA-unmatched, sex-mismatched, unrelated UCB transplantation after a reduced intensity-conditioning regimen (RICR) with engraftment as the primary endpoint. The median age of the patients was 55 years with a range of 28–67. Patients received one unit of UCB per 10 kg of recipient body weight (5–7 units). The median number of nucleated cells and CD34+ cells per kilogram of recipient body weight infused was 6.3 x 107 (range 3.8–10.0) (NC/kg) and 5.7 x 105 (range 1.1–11.9) (CD34/kg), respectively. Three patients expired before day 28 and were not evaluable for engraftment. Five of the remaining 7 patients showed increasing neutrophil counts. Fluorescent in situ hybridization (FISH) for the Y chromosome or HLA-typing showed only donor cells in the peripheral blood. After engraftment, HLA typing was done on 3 patients and their infused UCB units. All revealed the presence of a single HLA type concordant with one of the infused units. Moreover, the order of infusion did not influence which UCB unit engrafted. The engrafting UCB units were infused first or second in one case and fourth in the other two. One patient transplanted for refractory acute lymphoblastic leukemia (ALL) survives in continuous complete remission 4 years after transplant. He engrafted with one UCB unit, is fully hematologically reconstituted, has no evidence of graft-versus-host disease (GVHD), and takes no immunosuppressive medication. HLA typing reveals that the recipient and the engrafted cord blood match at only one HLA-B locus using conventional 6 antigen typing (A, B, and DR). Although engraftment was not accelerated, it did occur in the majority of evaluable patients. Long-term disease-free survivorship without debilitating GVHD is possible in patients with refractory hematological malignancy who receive unmatched multiple unit UCB.