Trial Information

A Phase II Study Of Pooled Unrelated Donor Umbilical Cord Blood (UCB) Transplant For Patients With Hematologic Malignancies Needing Allogeneic Stem Cell Transplant But Do Not Have A Related HLA-Matched Donor

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.