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 journalArticle

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

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KIR Receptors
Unrelated Donors
B-Cell Chronic Lymphocytic Leukemia
Leukemia
Bone Marrow
Genotype
Transplants
Research
Cell Transplantation
Tissue Donors
Survival
Graft vs Host Disease
Recurrence
Donor Selection
Mortality
Proportional Hazards Models
Haplotypes
Patient Selection
Disease-Free Survival
Disease Progression

Keywords

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

Cite this

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

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 5, 05.2019, p. 949-954.

Research output: Contribution to journalArticle

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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.",
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AU - Bachanova, Veronika

AU - Weisdorf, Daniel J.

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AU - Marsh, Steven G.E.

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AU - Haagenson, Michael D.

AU - Spellman, Stephen R.

AU - Lee, Stephanie J.

AU - Guethlein, Lisbeth A.

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