Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation

Ronald M. Sobecks, Tao Wang, Medhat Askar, Meighan M. Gallagher, Michael Haagenson, Stephen Spellman, Marcelo Fernandez-Vina, Karl Johan Malmberg, Carlheinz Müller, Minoo Battiwalla, James Gajewski, Michael R. Verneris, Olle Ringdén, Susana Marino, Stella Davies, Jason Dehn, Martin Bornhäuser, Yoshihiro Inamoto, Ann Woolfrey, Peter ShawMarilyn Pollack, Daniel Weisdorf, Jeffrey Milller, Carolyn Hurley, Stephanie J. Lee, Katharine Hsu

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P =002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2+ patients. AML patients with KIR2DS1+, HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = 002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.

    Original languageEnglish (US)
    Pages (from-to)1589-1596
    Number of pages8
    JournalBiology of Blood and Marrow Transplantation
    Volume21
    Issue number9
    DOIs
    StatePublished - Sep 1 2015

    Fingerprint

    KIR Receptors
    Cell Transplantation
    Genotype
    Unrelated Donors
    Tissue Donors
    Graft vs Host Disease
    Ligands
    Natural Killer Cells
    Myelodysplastic Syndromes
    Acute Myeloid Leukemia
    Recurrence
    Mortality

    Keywords

    • AML/MDS
    • Killer immunoglobulin-like receptor (KIR)
    • Reduced-intensity conditioning HCT

    ASJC Scopus subject areas

    • Transplantation
    • Hematology

    Cite this

    Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation. / Sobecks, Ronald M.; Wang, Tao; Askar, Medhat; Gallagher, Meighan M.; Haagenson, Michael; Spellman, Stephen; Fernandez-Vina, Marcelo; Malmberg, Karl Johan; Müller, Carlheinz; Battiwalla, Minoo; Gajewski, James; Verneris, Michael R.; Ringdén, Olle; Marino, Susana; Davies, Stella; Dehn, Jason; Bornhäuser, Martin; Inamoto, Yoshihiro; Woolfrey, Ann; Shaw, Peter; Pollack, Marilyn; Weisdorf, Daniel; Milller, Jeffrey; Hurley, Carolyn; Lee, Stephanie J.; Hsu, Katharine.

    In: Biology of Blood and Marrow Transplantation, Vol. 21, No. 9, 01.09.2015, p. 1589-1596.

    Research output: Contribution to journalArticle

    Sobecks, RM, Wang, T, Askar, M, Gallagher, MM, Haagenson, M, Spellman, S, Fernandez-Vina, M, Malmberg, KJ, Müller, C, Battiwalla, M, Gajewski, J, Verneris, MR, Ringdén, O, Marino, S, Davies, S, Dehn, J, Bornhäuser, M, Inamoto, Y, Woolfrey, A, Shaw, P, Pollack, M, Weisdorf, D, Milller, J, Hurley, C, Lee, SJ & Hsu, K 2015, 'Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation', Biology of Blood and Marrow Transplantation, vol. 21, no. 9, pp. 1589-1596. https://doi.org/10.1016/j.bbmt.2015.05.002
    Sobecks, Ronald M. ; Wang, Tao ; Askar, Medhat ; Gallagher, Meighan M. ; Haagenson, Michael ; Spellman, Stephen ; Fernandez-Vina, Marcelo ; Malmberg, Karl Johan ; Müller, Carlheinz ; Battiwalla, Minoo ; Gajewski, James ; Verneris, Michael R. ; Ringdén, Olle ; Marino, Susana ; Davies, Stella ; Dehn, Jason ; Bornhäuser, Martin ; Inamoto, Yoshihiro ; Woolfrey, Ann ; Shaw, Peter ; Pollack, Marilyn ; Weisdorf, Daniel ; Milller, Jeffrey ; Hurley, Carolyn ; Lee, Stephanie J. ; Hsu, Katharine. / Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation. In: Biology of Blood and Marrow Transplantation. 2015 ; Vol. 21, No. 9. pp. 1589-1596.
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    abstract = "Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95{\%} CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P =002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2+ patients. AML patients with KIR2DS1+, HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95{\%} CI, 1.4 to 4.2; P = 002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.",
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    AU - Askar, Medhat

    AU - Gallagher, Meighan M.

    AU - Haagenson, Michael

    AU - Spellman, Stephen

    AU - Fernandez-Vina, Marcelo

    AU - Malmberg, Karl Johan

    AU - Müller, Carlheinz

    AU - Battiwalla, Minoo

    AU - Gajewski, James

    AU - Verneris, Michael R.

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    AU - Marino, Susana

    AU - Davies, Stella

    AU - Dehn, Jason

    AU - Bornhäuser, Martin

    AU - Inamoto, Yoshihiro

    AU - Woolfrey, Ann

    AU - Shaw, Peter

    AU - Pollack, Marilyn

    AU - Weisdorf, Daniel

    AU - Milller, Jeffrey

    AU - Hurley, Carolyn

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    AU - Hsu, Katharine

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