Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 25, Issue 5, Pages 949-954Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2018.12.763
Keywords
Chronic lymphocytic leukemia; KIR; Allogeneic transplantation; Genotype; NK cells
Categories
Funding
- National Center for Advancing Translational Sciences
- National Institutes of Health (NIH) [UL1TR000114]
- NCI [P01 111412, 1U24HL138660]
- NIH [P30 CA77598]
- Public Health Service from the National Cancer Institute (NCI) [5U24CA076518]
- National Heart, Lung and Blood Institute (NHLBI) [5U24CA076518]
- National Institute of Allergy and Infectious Diseases [5U24CA076518]
- NHLBI [1U24HL138660]
- Health Resources and Services Administration [HHSH250201700006C]
- Office of Naval Research [N00014-17-1-2388, N00014-17-1-2850, N00014-18-1-2045]
- Adaptive Biotechnologies
- Amgen, Inc.
- 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
- Medical College of Wisconsin
- Merck Co, Inc.
- Mesoblast
- MesoScale Diagnostics, Inc.
- Millennium
- 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
- University of Minnesota
Ask authors/readers for more resources
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. (C) 2019 American Society for Blood and Marrow Transplantation.
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