KIR Donor Selection: Feasibility in Identifying better Donors

the participating center writing committee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We previously reported that acute myelogenous leukemia (AML) transplants using killer cell immunoglobulin-type receptor (KIR) B haplotype better or best (≥2 B activating gene loci ± Cen B/B) unrelated donors (URDs) yield less relapse and better survival. In this prospective trial we evaluated 535 AML searches from 14 participating centers with centralized donor KIR genotyping for donor selection. This represented 3% to 48% of all AML searches (median 20%) per center, totaling 3 to 172 patients (median 22) per center. Donor KIR genotype was reported at a median of 14 days after request (≤26 days for 76% of searches). In 535 searches, 2080 donors were requested for KIR genotyping (mean 4.3 per search); and a median of 1.8 (range, 0 to 4.5) per search were KIR typed. Choosing more donors for confirmatory HLA and KIR haplotype identification enriched the likelihood of finding KIR better or best donors. The search process identified a mean of 30% KIR better or best donors; the success ranged from 24% to 38% in the 11 centers enrolling ≥8 patients. More donors requested for KIR genotyping increased the likelihood of identifying KIR better or best haplotype donors. Of the 247 transplants, 9.3% used KIR best, 19% used KIR better, and 48% used KIR neutral donors while 24% used a non–KIR-tested donor. KIR genotyping did not delay transplantation. The time from search to transplant was identical for transplants using a KIR-genotyped versus a non–KIR-genotyped donor. Prospective evaluation can rapidly identify KIR favorable genotype donors, but choosing more donors per search would substantially increase the likelihood of having a KIR best or better donor available for transplantation. Transplant centers and donor registries must both commit extra effort to incorporate new characteristics (beyond HLA, age, and parity) into improved donor selection. Deliberate efforts to present additional genetic factors for donor selection will require novel procedures.

Original languageEnglish (US)
Pages (from-to)e28-e32
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number1
DOIs
StatePublished - Jan 2019

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Donor Selection
Immunoglobulins
Tissue Donors
Transplants
Acute Myeloid Leukemia
Haplotypes
Transplantation
Genotype
Unrelated Donors

Keywords

  • Allogeneic hematopoietic cell transplant
  • HLA
  • KIR
  • Unrelated donor selection

Cite this

KIR Donor Selection : Feasibility in Identifying better Donors. / the participating center writing committee.

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 1, 01.2019, p. e28-e32.

Research output: Contribution to journalArticle

the participating center writing committee. / KIR Donor Selection : Feasibility in Identifying better Donors. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 1. pp. e28-e32.
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abstract = "We previously reported that acute myelogenous leukemia (AML) transplants using killer cell immunoglobulin-type receptor (KIR) B haplotype better or best (≥2 B activating gene loci ± Cen B/B) unrelated donors (URDs) yield less relapse and better survival. In this prospective trial we evaluated 535 AML searches from 14 participating centers with centralized donor KIR genotyping for donor selection. This represented 3{\%} to 48{\%} of all AML searches (median 20{\%}) per center, totaling 3 to 172 patients (median 22) per center. Donor KIR genotype was reported at a median of 14 days after request (≤26 days for 76{\%} of searches). In 535 searches, 2080 donors were requested for KIR genotyping (mean 4.3 per search); and a median of 1.8 (range, 0 to 4.5) per search were KIR typed. Choosing more donors for confirmatory HLA and KIR haplotype identification enriched the likelihood of finding KIR better or best donors. The search process identified a mean of 30{\%} KIR better or best donors; the success ranged from 24{\%} to 38{\%} in the 11 centers enrolling ≥8 patients. More donors requested for KIR genotyping increased the likelihood of identifying KIR better or best haplotype donors. Of the 247 transplants, 9.3{\%} used KIR best, 19{\%} used KIR better, and 48{\%} used KIR neutral donors while 24{\%} used a non–KIR-tested donor. KIR genotyping did not delay transplantation. The time from search to transplant was identical for transplants using a KIR-genotyped versus a non–KIR-genotyped donor. Prospective evaluation can rapidly identify KIR favorable genotype donors, but choosing more donors per search would substantially increase the likelihood of having a KIR best or better donor available for transplantation. Transplant centers and donor registries must both commit extra effort to incorporate new characteristics (beyond HLA, age, and parity) into improved donor selection. Deliberate efforts to present additional genetic factors for donor selection will require novel procedures.",
keywords = "Allogeneic hematopoietic cell transplant, HLA, KIR, Unrelated donor selection",
author = "{the participating center writing committee} and Weisdorf, {Daniel J} and Tao Wang and Elizabeth Trachtenberg and Cooley, {Sarah A} and Cynthia Vierra-Green and Stephen Spellman and Ashley Spahn and Jenny Vogel and Hati Kobusingye and Todd Fehninger and Ann Woolfrey and Steven Devine and Maureen Ross and Waller, {Edmund K.} and Ronald Sobecks and Peter Parham and Guethlein, {Lisbeth A.} and Marsh, {Steven G.E.} and Miller, {Jeffrey S}",
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AU - Cooley, Sarah A

AU - Vierra-Green, Cynthia

AU - Spellman, Stephen

AU - Spahn, Ashley

AU - Vogel, Jenny

AU - Kobusingye, Hati

AU - Fehninger, Todd

AU - Woolfrey, Ann

AU - Devine, Steven

AU - Ross, Maureen

AU - Waller, Edmund K.

AU - Sobecks, Ronald

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AB - We previously reported that acute myelogenous leukemia (AML) transplants using killer cell immunoglobulin-type receptor (KIR) B haplotype better or best (≥2 B activating gene loci ± Cen B/B) unrelated donors (URDs) yield less relapse and better survival. In this prospective trial we evaluated 535 AML searches from 14 participating centers with centralized donor KIR genotyping for donor selection. This represented 3% to 48% of all AML searches (median 20%) per center, totaling 3 to 172 patients (median 22) per center. Donor KIR genotype was reported at a median of 14 days after request (≤26 days for 76% of searches). In 535 searches, 2080 donors were requested for KIR genotyping (mean 4.3 per search); and a median of 1.8 (range, 0 to 4.5) per search were KIR typed. Choosing more donors for confirmatory HLA and KIR haplotype identification enriched the likelihood of finding KIR better or best donors. The search process identified a mean of 30% KIR better or best donors; the success ranged from 24% to 38% in the 11 centers enrolling ≥8 patients. More donors requested for KIR genotyping increased the likelihood of identifying KIR better or best haplotype donors. Of the 247 transplants, 9.3% used KIR best, 19% used KIR better, and 48% used KIR neutral donors while 24% used a non–KIR-tested donor. KIR genotyping did not delay transplantation. The time from search to transplant was identical for transplants using a KIR-genotyped versus a non–KIR-genotyped donor. Prospective evaluation can rapidly identify KIR favorable genotype donors, but choosing more donors per search would substantially increase the likelihood of having a KIR best or better donor available for transplantation. Transplant centers and donor registries must both commit extra effort to incorporate new characteristics (beyond HLA, age, and parity) into improved donor selection. Deliberate efforts to present additional genetic factors for donor selection will require novel procedures.

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