Targeting the IPA and Matching for the Non-Inherited Maternal Antigen for Haplo-Cord Transplantation

This is a clinical trial for subjects with hematologic malignancies ( acute leukemia, myeloproliferative disorders, lymphoma, myeloma) who are in need of a donor stem cell transplant, and for whom an umbilical cord blood transplant is thought to be the best option. As donors for allogeneic transplant, we typically try to use related family members, such as brothers or sisters, or volunteer donors who are 'HLA matched', i.e. share similar proteins on their cells. This study is for subjects for whom such a matched sibling donor or a matched unrelated donor is not available. For such subjects a commonly used transplant procedure is to use stem cells from one or two umbilical cords (UCB) from a newborn. These umbilical cord blood grafts, despite not completely matching the recipient, cause few problems with graft vs host disease (a common complication of transplant). But they tend to grow very slowly and subjects often have very prolonged hospital stays and are at high risk for complications due to low blood counts. Umbilical cord blood transplant will be the standard arm for this protocol. This study uses a new method of bone marrow transplantation called combined haplo-identical cord (haplo-cord) transplantation. In this procedure, cells from a related donor who shares half of the HLA proteins ( haplo-identical) are collected from the blood, as well as cells from an umbilical cord, and then both are transplanted. It is hoped that by using cells from a haplo-identical relative, subjects will have a faster recovery and require fewer transfusions. Over time the haplo-identical cells from the relative are replaced by the cells from the cord blood. The combined transplantation of haplo-identical stem cells and cord blood has previously been used in approximately 60 subjects with very encouraging results. Traditionally it has been felt that the most important determinant of outcome of an UCB stem cell transplant is the cord blood cell dose. The second determinant is the degree of matching between donor and recipient. Many times, we have difficulty identifying UCB units of sufficient cell dose that are well matched. Of interest,in our prior study of haplo-cord SCT indicated outcomes seemed independent of the UCB cell dose. If this preliminary observation is correct, we may be able to improve the outcomes of haplo cord transplant further by accepting lower threshold UCB doses and rather focusing on optimal matching (including matching for HLA and another characteristic called IPA). This is the primary objective of this study.