KIR Donor Selection: Feasibility in Identifying better Donors

• Type of Material: Article
• Authors: Daniel Weisdorf, University of Minnesota Twin Cities; Sarah Cooley, University of Minnesota Twin Cities; Tao Wang, Medical College of Wisconsin; Elizabeth Trachtenberg, Children's Hospital Oakland Research Institute; Michael D. Haagenson, Center for International Blood and Marrow Transplant Research; Cynthia Vierra-Green, Center for International Blood and Marrow Transplant Research; Stephen Spellman, Center for International Blood and Marrow Transplant Research; Ashley Spahn, Center for International Blood and Marrow Transplant Research; Jenny Vogel, Center for International Blood and Marrow Transplant Research; Hati Kobusingye, Center for International Blood and Marrow Transplant Research; Todd Fehninger, Washington University St. Louis; Ann Woolfrey, Fred Hutchinson Cancer Research Center; Steven Devine, Ohio State University; Maureen Ross, Roswell Park Cancer Institute; Edmund Waller, Emory University; Ronald Sobecks, Cleveland Clinic Foundation; Peter Parham, Stanford University; Lisbeth A. Guethlein, Stanford University; Steven G. E. Marsh, Anthony Nolan Trust; Jeffrey Miller, University of Minnesota Twin Cities
• Language: English
• Date: 2019-01-01
• Publisher: American Society for Transplantation and Cellular Therapy
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2018.08.022
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• Volume: 25
• Issue: 1
• Start Page: e28
• End Page: e32
• Grant/Funding Information: Supported in part by a grant from the National Cancer Institute PO1 CA 111412
• Keywords: Adolescent; Humans; Unrelated Donors; Adult; Hematopoietic Stem Cell Transplantation; Haplotypes; Allogeneic hematopoietic cell transplant; Donor Selection; Receptors, KIR; HLA; Prospective Studies; KIR; Female; Unrelated donor selection; Leukemia, Myeloid, Acute; Feasibility Studies; Male; Middle Aged
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

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.