The New York Blood Center’s National Cord Blood Program has provided cord blood units for about one fourth of the world’s transplants of unrelated cord blood to date. With indispensable help from the staff of the Transplant Centers, we have garnered extensive data on clinical outcomes from these transplants. This information has helped evaluate factors that affect transplant outcome in both children and adults. Results have been published in several medical journals (to see the list of publications, visit the News
& Articles section).
Research collaborations include:
Comparisons of Transplant Outcomes: Cord Blood and Bone Marrow
With the Center for International Blood and Marrow Transplant Research (CIBMTR) – a comparison of unrelated cord blood and bone marrow transplants in children. Presented by Mary Horowitz, MD at the 2001 meeting of American Society of Hematology (ASH) and (updated) published by Mary Eapen, MD in Lancet, 2007.
Also with CIBMTR – a comparison of unrelated cord blood transplants in adults, presented by Mary Laughlin, MD at the 2003 ASH meeting and published in 2004 (NEJM). Further comparison on unrelated CB, unrelated BM and unrelated PB stem cell grafts in adult patients was presented by Mary Eapen MD at the 2008 meeting of the American Society of Hematology (ASH).
Expansion of Stem Cell Numbers in Cord Blood Units:
Because of the relatively small number of cells in a cord blood collection, and the known relationship between the cell dose and the success of a cord blood transplant, there is a need to increase, in vitro, the number of true stem cells in cord blood grafts, so that they will engraft faster. If successful, expanding the number of stem cells may benefit full-grown adolescents and adults who require large numbers of stem cells in order to engraft quickly. We collaborate in a clinical trial of cell expansion with GamidaCell – a study to assess the safety of growing cells in the laboratory to expand the number of stem cells using GamidaCell method. (Ongoing study).
Recently, a study reported culturing stem and progenitor cell populations in cord blood grafts cells with Notch ligand (Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution, by Colleen Delaney, et.al, in Nature Medicine 16, 232 - 236 (2010). Faster engraftment was seen in a small number of patients that received the expanded cells. This approach may help overcome the cell dose limitation of cord blood transplantation.
Two unit cord blood transplants in adults:
We have collaborated with several transplant centers (mainly the University of Minnesota and Memorial Sloan Kettering Cancer Center in New York), in the evaluation of another strategy to overcome the cell dose limitations of cord blood transplantation in adults. The approach is to transplant two or more cord blood units at the same time. Double unit transplants are also being perfromed with a reduced, less toxic conditioning regimen (Ref: Barker JN, et al; Blood, 2003).
Another strategy is to transplant cord blood simultaneously with T-cell depleted, half-matched (haploidentical) bone marrow (Ref: Fernandez MN, et al; Experimental Hematology, 2003). According to this study, the T-cell depleted haploidentical bone marrow would engraft quickly and provide early protection from infection. The cord blood engraft later and eventually, become the only donor providing hematopoietic reconstitution, and may offer the long-term benefit of reduced risk of graft vs. host disease.
Non-inherited Maternal Antigens – role in HLA mismatched transplants:
The problems caused by the enormous extent of HLA polymorphism could be palliated by taking advantage of the fact that during pregnancy, mother and fetus exchange cells, which can lead to a life-long chimerism for both. The developing immune system of the fetus, faced by maternal antigens it has not inherited (the Non Inherited Maternal Antigens or NIMAs), recognizes them as foreign and mounts an immune response, which is actively suppressed by so called T regulator cells (T reg). Nevertheless the “memory” of these activated cells, which are normally able to kill (lyse) cells carrying the NIMA, (called cytotoxic T cells or CTL’s) remains, as well as the T-reg. Those memory cells (in cord blood T cells and almost certainly also adult T cells) are reactivated when exposed to cells expressing the NIMA of the cord blood donor. In November, 2009, in collaboration with Prof. Jon J van Rood and his group (Eurotransplant) in Leiden, NCBP reported an exploration of the potential influence of NIMAs in cord blood transplantation. In this study, patients that received cord blood transplants that were HLA-mismatched but NIMA (Non-Inherited Maternal Antigen) matched, had improved neutrophil recovery, reduced transplant related mortality (TRM) and improved survival compared to those that received HLA mismatched, not NIMA matched cord blood units. We hypothesized that the mechanism for the improved TRM was that the memory T cells in the donor, including the CTL’s, may be activated, so that they could kill the leukemic cells carrying the same antigens as the NIMA, potentially preventing leukemic relapse. In parallel, the regulatory cells may also be re-activated, preventing the development of serious graft versus host disease.