Donor Killer Cell Immunoglobulin-Like Receptor Genotype Does Not Improve Graft-versus-Leukemia Responses in Chronic Lymphocytic Leukemia after Unrelated Donor Transplant: A Center for International Blood and Marrow Transplant Research Analysis

Veronika Bachanova, Daniel J. Weisdorf, Tao Wang, Steven G.E. Marsh, Nezih Cereb, Michael D. Haagenson, Stephen R. Spellman, Stephanie J. Lee, Lisbeth A. Guethlein, Peter Parham, Jeffrey S. Miller, Sarah A. Cooley

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Allogeneic hematopoietic cell transplantation (alloHCT)remains the sole curative therapy for patients with chronic lymphocytic leukemia (CLL), leading to 40% to 45% long-term survival. The impact of donor killer immunoglobulin-like receptor (KIR)genotype on outcomes of unrelated donor (URD)alloHCT for CLL is unknown. We examined 573 adult URD CLL recipient pairs. KIR genotype (presence/absence)was determined for each donor, and comprehensive modeling of interactions with recipient HLA class I loci (KIR ligands)was used to evaluate their effect on relapse and survival. Recipients had a median age of 56 years, and most were not in remission (65%). Both 8/8 HLA-matched (81%)or 7/8 HLA matched grafts (19%)were studied. Factors associated with improved overall survival (OS)were reduced-intensity conditioning (hazard ratio [HR]of death,.76)and good performance status (HR,.46), whereas alloHCT in nonremission (HR, 1.96)and mismatched donors (HR, 2.01)increased mortality. No models demonstrated a relationship between donor KIR genotype and transplant outcomes. Cox regression models comparing donors with A/A versus B/x KIR haplotypes and those with KIR gene content scores of 0 versus 1 versus ≥2 yielded similar rates of nonrelapse mortality, relapse, acute graft-versus-host disease (GVHD), and chronic GVHD and the same progression-free survival and OS. Relapse risk was not different for grafts from donors with KIR3DL1 transplanted into HLA C1/1 versus C2 recipients. This large analysis failed to demonstrate an association between URD KIR genotype and transplant outcome for patients with CLL, and thus KIR genotyping should not be used as a donor selection criterion in this setting.

Original languageEnglish (US)
Pages (from-to)949-954
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number5
DOIs
StatePublished - May 2019

Bibliographical note

Funding Information:
Funding and Financial disclosures: Research reported in this publication was supported by the National Center for Advancing Translational Sciences and the National Institutes of Health (NIH)Award Number UL1TR000114 (to V.B.)and NCI P01 111412 (to D.J.W. T.W. S.G.E.M. E.T. M.H. S.R.S. L.A.G. M.L. P.P. J.S.M. and S.C.). This work was supported in part by NIH P30 CA77598 using the Masonic Cancer Center, University of Minnesota Oncology Medical Informatics and Services shared resource. The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 1U24HL138660 from NHLBI and NCI; contract HHSH250201700006C with Health Resources and Services Administration; 3 grants (N00014-17-1-2388, N00014-17-1-2850, and N00014-18-1-2045)from the Office of Naval Research; and grants from Adaptive Biotechnologies; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; *CytoSen Therapeutics, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite Pharma, Inc.; Medac, GmbH; *Mediware; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Pharmaceuticals Corporation; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; and University of Minnesota. (Asterisks denote Corporate Members.)The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government. Conflict of interest statement: There are no conflicts of interest to report. Authorship statement: V.B. D.J.W. J.S.M. and S.C. contributed to the study design, analyzed and interpreted data, and wrote the manuscript. S.R.S. S.J.L. and M.D.H. contributed to the study design, sample procurement, data management, and manuscript editing. T.W. performed the biostatistical analyses for the study. E.T. and N.C. performed KIR genotyping. S.G.E.M. L.A.G. and P.P. reviewed and edited the manuscript.

Funding Information:
Funding and Financial disclosures: Research reported in this publication was supported by the National Center for Advancing Translational Sciences and the National Institutes of Health (NIH) Award Number UL1TR000114 (to V.B.) and NCI P01 111412 (to D.J.W., T.W., S.G.E.M., E.T., M.H., S.R.S., L.A.G., M.L., P.P., J.S.M., and S.C.). This work was supported in part by NIH P30 CA77598 using the Masonic Cancer Center, University of Minnesota Oncology Medical Informatics and Services shared resource. The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 1U24HL138660 from NHLBI and NCI; contract HHSH250201700006C with Health Resources and Services Administration; 3 grants (N00014-17-1-2388, N00014-17-1-2850, and N00014-18-1-2045) from the Office of Naval Research; and grants from Adaptive Biotechnologies; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; *CytoSen Therapeutics, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite Pharma, Inc.; Medac, GmbH; *Mediware; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Pharmaceuticals Corporation; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; and University of Minnesota. (Asterisks denote Corporate Members.) The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government. Financial disclosure: See Acknowledgments on page 5.

Funding Information:
Funding and Financial disclosures: Research reported in this publication was supported by the National Center for Advancing Translational Sciences and the National Institutes of Health (NIH) Award Number UL1TR000114 (to V.B.) and NCI P01 111412 (to D.J.W., T.W., S.G.E.M., E.T., M.H., S.R.S., L.A.G., M.L., P.P., J.S.M., and S.C.). This work was supported in part by NIH P30 CA77598 using the Masonic Cancer Center, University of Minnesota Oncology Medical Informatics and Services shared resource. The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases ; Grant/Cooperative Agreement 1U24HL138660 from NHLBI and NCI; contract HHSH250201700006C with Health Resources and Services Administration; 3 grants (N00014-17-1-2388, N00014-17-1-2850, and N00014-18-1-2045) from the Office of Naval Research ; and grants from Adaptive Biotechnologies; *Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; *CytoSen Therapeutics, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite Pharma, Inc.; Medac, GmbH; *Mediware; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Pharmaceuticals Corporation; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; and University of Minnesota. (Asterisks denote Corporate Members.) The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government.

Publisher Copyright:
© 2019 American Society for Blood and Marrow Transplantation

Keywords

  • Allogeneic transplantation
  • Chronic lymphocytic leukemia
  • Genotype
  • KIR
  • NK cells

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