Abstract
This review of the immunogenetics of cord blood transplantation attempts to highlight the connections between classical studies and conclusions of the tissue transplantation field as a scholarly endeavor, exemplified by the work of Professor Hoecker, with the motivations and some recent and key results of clinical cord blood transplantation. The authors review the evolution of understanding of transplantation biology and find that the results of the application of cord blood stem cells to Transplantation Medicine are consistent with the careful experiments of the pioneers in the field, from the results of tumor and normal tissue transplants, histocompatibility immunogenetics, to cell and molecular biology. Recent results of the National Cord Blood Program of the New York Blood Center describe the functioning in cord blood transplantation of factors, well known in transplantation immunogenetics, like the Fl anti-parent effect and the tolerance-like status of donors produced by non-inherited maternal HLA antigens. Consideration of these factors in donor selection strategies can improve the prognosis of transplantation by characterizing "permissibility" in HLA-incompatible transplantation thereby increasing the probability of survival and reducing the likelihood of leukemic relapse.
Highlights
Tissue and solid organ transplantation are well-established therapeutic technologies in current medical practice and are performed on many thousands of patients every year
The immunogenetic properties of cord blood are predictable from its cellular composition and age in the context of an evolving histocompatibility system and are not surprising in the context of the evolving understanding of that system’s biology
The broad immunologic bases of allotransplantation are reasonably well understood, important problems still remain to be solved properly. In this brief review of cord blood as source of hematopoietic tissue for bone marrow replacement (Rubinstein, 2005) and its immunogenetic underpinnings, we will examine the biological background of transplantation immunogenetics in general and some current challenges in overcoming the clinical problems of cord blood transplantation
Summary
Tissue (mostly bone marrow) and solid organ transplantation (kidney, liver, heart) are well-established therapeutic technologies in current medical practice and are performed on many thousands of patients every year. In collaboration with van Rood’s group, the National Cord Blood Program of the New York Blood Center has encountered evidence that a defined HLA mismatch between donor and recipient may not decrease engraftment or survival and be “permissible”, when the mismatched HLA antigen of the recipient was present in the donor’s mother’s HLA type as a NIMA (van Rood et al, 2009) In this clinical situation, a transplant where the one- or two-HLA mismatch co-existed with a NIMA match, had significantly faster engraftment (p=0.043) and better survival: transplant-related mortality (TRM) (p=0.012) and overall survival (p=0.029), especially in patients >10 years old. Cord blood Transplants with bidirectional or unidirectional HLA mismatches (MM): endpoint analyses by Cox Regression. (See notes below)
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