Pooled Unrelated Donor Umbilical Cord Blood Transplant For Hematologic Malignancy Needing Allogeneic Stem Cell Transplant Without Related HLA-Match

Hematopoietic stem cell (HSC) transplantation, using human HLA-matched sibling or unrelated bone marrow or peripheral blood stem cell donor, has been used successfully to treat patients with high-risk or relapsed hematologic malignancies. However, use of this therapy has been limited by availability of fully HLA-matched donors, despite the increasing size of unrelated donor registries. For those transplanted with unrelated donor marrow stem cells, increased HLA disparity adversely affects survival due to increased risks of severe acute and chronic graft-versus-host disease (GVHD) and opportunistic infection. Only young recipients are able to tolerate a single HLA-A, B, DRB1 mismatch in this setting (1-3). To potentially extend the donor pool, UCB has been used as an alternative source of HSC. Since the first unrelated donor UCB transplant in 1993, UCB transplants have been performed worldwide. It has been found to produce outcome comparable to those from matched unrelated HSC in patients with hematologic malignancies (4). It has been shown that cryopreserved unrelated UCB from 0 to 3 HLA-A, B, DRB1-mismatched donors contains sufficient HSC to engraft most pediatrics and some adult patients (5-10). Unfortunately, the use of UCB transplant is limited by the small number of HSC in each of the cord blood unit. This is particularly a problem for adult patients. It is now possible to pool UBC so that adequate cell numbers are available for adult transplant (11). UBC is rapidly availability and has very low rate of contamination with herpes group viruses. UCB transplant results in a low incidence of both severe acute GVHD and extensive chronic GVHD, despite the use of grafts with substantial donor-recipient HLA disparity (5-10). The following conditioning regimens will be used, depending on the underlying hematologic malignancies. Conditioning regimens with Busulfan/clofarabine and with fludarabine/melphalan will be used for all patients except those with Non-Hodgkin's lymphoma when the conditioning regimen of BCNU, Etoposide, ARA-C and Melphalan will be used. GVHD prophylaxis of oral tacrolimus will be used, depending on the development of GVHD and the clinical conditions of the patients, tacrolimus may be tapered and discontinued by six months after transplant. The hematopoietic stem cells from the donors will be infused within 48-72 hours of completing the chemotherapy. The patients will receive supportive care as indicated including antibiotics, antivirals, antifungals, anti-seizure, anti-emetic medications and other medications as necessary. In addition patients will receive irradiated blood products for support as necessary.CMV negative recipient transplant will receive only CMV- blood products. Neutrophil engraftment will be defined as the day on which the ANC rises to \> 500 cells/ml for two consecutive days. Platelet engraftment will be defined as the first day on which the platelet count rises to \> 20,000/ml over a 7-day interval without transfusion support.