Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome

Neal Flomenberg, Lee Ann Baxter-Lowe, Dennis Confer, Marcelo Fernandez-Vina, Alexandra Filipovich, Mary Horowitz, Carolyn Hurley, Craig Kollman, Claudio Anasetti, Harriet Noreen, Ann Begovich, William Hildebrand, Effie Petersdorf, Barbara Schmeckpeper, Michelle Setterholm, Elizabeth Trachtenberg, Thomas Williams, Edmond Yunis, Daniel Weisdorf

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Abstract

Outcome of unrelated donor marrow transplantation is influenced by donor-recipient matching for HLA. Prior studies assessing the effects of mismatches at specific HLA loci have yielded conflicting results. The importance of high-resolution matching for all HLA loci has also not been established. We therefore examined the effects of HLA matching (low or high resolution or both) on engraftment, graft-versus-host disease (GVHD), and mortality in 1874 donor-recipient pairs retrospectively typed at high resolution for HLA-A, -B, -C, -DRB1, -DQ, and -DP. Mismatches at HLA-A, -B, -C, and -DRB1 each had similar adverse effects on mortality. Only HLA-A mismatches demonstrated significant adverse effects on GVHD. These adverse effects on outcome were more evident in transplants with low-resolution versus only high-resolution mismatches. Mismatches for HLA-DQ or -DP did not significantly affect outcome. When high-resolution mismatches at HLA-A, -B, -C, and -DRB1 were considered together, adverse effects on survival and GVHD were observed. We therefore conclude that matching for HLA-C should be incorporated into algorithms for unrelated donor selection. High-resolution mismatches at HLA-A, -B, -C, and -DRB1 adversely affect outcome, but less so than low-resolution mismatches. When clinical circumstances allow, high-resolution class I typing may help optimize donor selection and improve outcome.

Original languageEnglish (US)
Pages (from-to)1923-1930
Number of pages8
JournalBlood
Volume104
Issue number7
DOIs
StatePublished - Oct 1 2004

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    Flomenberg, N., Baxter-Lowe, L. A., Confer, D., Fernandez-Vina, M., Filipovich, A., Horowitz, M., Hurley, C., Kollman, C., Anasetti, C., Noreen, H., Begovich, A., Hildebrand, W., Petersdorf, E., Schmeckpeper, B., Setterholm, M., Trachtenberg, E., Williams, T., Yunis, E., & Weisdorf, D. (2004). Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood, 104(7), 1923-1930. https://doi.org/10.1182/blood-2004-03-0803