Risk assessment in haematopoietic stem cell transplantation: Histocompatibility

doi:10.1016/j.beha.2006.09.001

Best Practice & Research Clinical Haematology

Volume 20, Issue 2, June 2007, Pages 155-170

https://doi.org/10.1016/j.beha.2006.09.001 Get rights and content

Consideration of potential donors for transplantation includes a rigorous assessment of the availability and HLA-match status of family members, and the identification of suitable unrelated donors when related donors are not available. Because HLA gene products provoke host-versus-graft and graft-versus-host alloimmune responses, HLA matching serves a critical preventive role in lowering risks of graft failure and graft-versus-host disease (GVHD). At the same time, graft-versus-leukemia effects associated with HLA mismatching may provide an immunological means to lower the recurrence of post-transplant disease in high-risk patients. The definition of a suitable allogeneic donor is ever changing, shaped not only by current typing technology for the known HLA genes but also by the specific transplant procedure. Increased safety of alternative donor hematopoietic cell transplantation (HCT) has been achieved in part through advances in the field of immunogenetics. Increased availability of HCT through the use of HLA-mismatched related and unrelated donors is feasible with a more complete understanding of permissible HLA mismatches and the role of NK-KIR genes in transplantation.

Section snippets

The genetics of the HLA and NK systems

The HLA genes reside within the 7.6-Mb extended region of the major histocompatibility complex (MHC) on chromosome 6p21, residence of over 100 loci involved in immune function.¹HLA-A, -B, -C, -DR, -DQ and -DP gene products (antigens) define histocompatibility important in allogeneic hematopoietic cell transplantation (HCT). A hallmark of HLA genes is their extensive polymorphism.² HLA diversity is a reflection of their primary function to bind and present antigenic peptides for recognition by

Haploidentical related HCT

The immediate availability of a family member to serve as a stem-cell donor makes haploidentical related HCT an attractive option for patients who lack an HLA genotypically identical sibling and for patients whose disease tempo does not afford the time required for conducting an unrelated donor search.*16, 17, 18, 19, 20, *21, 22, 23, 24 HLA disparity in haploidentical related HCT increases the risks of graft failure and GVHD (often hyperacute) and delays immune reconstitution, and early on

Graft-versus-leukemia effects: the role of HLA and NK-mediated alloreactivity

Graft-versus-leukemia effects in patients with clinical GVHD have provided an important anti-leukemia mechanism after allogeneic HCT75, 76, 77, 78, 79, 80 and provide the rationale for the use of therapeutic strategies for lowering post-transplant disease recurrence with donor lymphocyte infusion. Beneficial effects of HLA-DPB1 mismatching on lower post-transplant relapse are evident in patients transplanted for lymphoid malignancies.⁶³ GVL effects are observed after reduced-intensity and

Summary

Haploidentical related and unrelated donors provide an opportunity for patients to benefit from HCT when an HLA genotypically matched sibling is not available. The HLA factors responsible for graft failure and GVHD risk have been defined for the class I HLA-A, -B and -C and the class II HLA-DRB1, -DQB1 and -DPB1 genes. HLA mismatching is associated with increased risks of graft failure, GVHD and delayed immune reconstitution, but also with lower risk of disease recurrence. The definition of an

Conflict of interest statement

Dr Petersdorf declares that she has no conflict of interest.

Acknowledgements

Effie Petersdorf is supported by grants CA18029, CA100019, AI33484 and AI069197 from the National Institutes of Health. The author thanks Karen Carbonneau, Susan Greenman and Mari Malkki for preparation of the manuscript.

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2Risk assessment in haematopoietic stem cell transplantation: Histocompatibility

Section snippets

The genetics of the HLA and NK systems

Haploidentical related HCT

Graft-versus-leukemia effects: the role of HLA and NK-mediated alloreactivity

Summary

Conflict of interest statement

Acknowledgements

Human Immunology

Human Immunology

Blood

Blood

Immunology Today

Biology of Blood and Marrow Transplantation

Biology of Blood and Marrow Transplantation

Blood

Blood

Human Immunology

Transfusion Science

The American Journal of Medicine

Blood

Blood

Blood

Blood

Lancet

Blood

Human Immunology

Blood

Blood

Blood

Blood

Blood

Blood

Human Immunology

Blood

Blood

Biology of Blood and Marrow Transplantation

Immunity

Blood

Blood

Blood

Blood

Blood

Blood

Molecular Immunology

Gene map of the extended human MHC. (Review)

Nature Reviews. Genetics

Nature of polymorphism in HLA-A, -B, and -C molecules

Proceedings of the National Academy of Sciences of the United States of America

Polymorphism, recombination, and linkage disequilibrium within the HLA class II region

Journal of Immunology (Baltimore, Md.)

The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases (Review)

Immunological Reviews

HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry

Transplantation

HLA -A, -B, -DR haplotype frequencies in France – implications for recruitment of potential bone marrow donors

Transplantation

Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/Cw/DRB1/B3/B5/DQB1-matched donor?

Bone Marrow Transplantation

Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population

Molecular Biology & Evolution

Assessment of optimal size and composition of the U.S. National Registry of hematopoietic stem cell donors

Transplantation

The HLA Dictionary 2001: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens

European Journal of Immunogenetics

The extent of HLA class II allele level disparity in unrelated bone marrow transplantation: analysis of 1259 National Marrow Donor Program donor-recipient pairs

Bone Marrow Transplantation

2
Risk assessment in haematopoietic stem cell transplantation: Histocompatibility