During the last three decades, bone marrow transplantation (BMT) has become the standard care for the treatment of many hematological malignancies. The idea donor, one who possesses the same HLA-A, B, DR phenotype as that of the patient, is found less than 35% of the time among family members and less than 50% of the time among unrelated donors. Furthermore, minority patients have even lower probability of finding an HLA matched donor. The overall goals of this project are to evaluate the feasibility of finding unrelated matched donors for bone marrow transplant (BMT) patients as a function of HLA-A, B, DR phenotype, race and geographical location of recipient and donor, to develop projections which will facilitate management strategies for recruiting marrow donors on the basis of race and geographical location, and to develop tools which will permit analysis of clinical outcomes on the basis of the probability of haplotype match rather than phenotype match among unrelated BMT patients.
Specific aims of the project are to: (1) compare HLA polymorphism among various racial groups and in different geographical regions of the United States; (2) estimate the probability of finding a 6/6 HLA-A, B, DR match and 6/6 or 5/6 match various racial groups as well as for geographically defined groups; (3) estimate the number of donors required from each racial group and geographical region in order to achieve equal access among various racial groups: (4) assess the extent to which European and other foreign marrow donor registries can assist U.S. patients in finding a matched donor by contributing to the diversity of phenotypes represented in the registry: (5) evaluate HLA polymorphism using DNA typing data and to estimate the probability of finding an HLA match at the level of allele rather than antigen for each racial group; (6) evaluate the impact of changes in matching criteria based on molecular determinations of phenotype upon the probability of finding a matched donor for each racial group; (7) develop tools which permit evaluation of impact of genotype match on clinical outcomes among unrelated BMT patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056368-02
Application #
2392787
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1996-04-01
Project End
2001-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Utah
Department
Miscellaneous
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Bandeira-Melo, Christianne; Sugiyama, Kumiya; Woods, Lesley J et al. (2002) IL-16 promotes leukotriene C(4) and IL-4 release from human eosinophils via CD4- and autocrine CCR3-chemokine-mediated signaling. J Immunol 168:4756-63
Beatty, P G; Boucher, K M; Mori, M et al. (2000) Probability of finding HLA-mismatched related or unrelated marrow or cord blood donors. Hum Immunol 61:834-40
Mori, M; Beatty, P G; Graves, M et al. (1997) HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry. Transplantation 64:1017-27
Mori, M; Graves, M; Milford, E L et al. (1996) Computer program to predict likelihood of finding and HLA-matched donor: methodology, validation, and application. Biol Blood Marrow Transplant 2:134-44