Prospective KIR genotype evaluation of hematopoietic cell donors is feasible with potential to benefit patients with AML Journal Article

Authors: Shaffer, B. C.; Le Luduec, J. B.; Park, S.; Devlin, S.; Archer, A.; Davis, E.; Cooper, C.; Nhaissi, M.; Suri, B.; Wells, D.; Tamari, R.; Papadopoulos, E.; Jakubowski, A. A.; Giralt, S.; Hsu, K. C.
Article Title: Prospective KIR genotype evaluation of hematopoietic cell donors is feasible with potential to benefit patients with AML
Abstract: Donor KIR and recipient HLA combinations that minimize inhibition and favor activation of the NK repertoire are associated with improved outcomes after allogeneic hematopoietic cell transplantation (HCT) in patients with myeloid neoplasia. We prospectively evaluated a weighted donor ranking algorithm designed to prioritize HLA-compatible unrelated donors (URDs) with weak inhibitory KIR3DL1/HLA-Bw4 interaction, followed by donors with nontolerized activating KIR2DS1, and finally those with KIR centromeric B haplotype. During donor evaluation, we performed KIR genotyping and ranked 2079 URDs for 527 subjects with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Among all patients, 394 (75%) had at least 1 KIR-advantageous donor, and 263 (50%) underwent HCT. In patients with AML, KIR3DL1 weak inhibition provided protection from relapse. Compared with KIR3DL1-Weak Inhibiting donors, KIR3DL1-Noninteracting donors were associated with increased risk of relapse (HR, 2.97; 95% CI, 1.33-6.64; P = .008) and inferior event-free survival (EFS; HR, 2.14; 95% CI, 1.16-3.95; P = .015). KIR3DL1-Strong Inhibiting donors were associated with HR, 1.65 (95% CI, 0.66-4.08; P = .25) for AML relapse and HR, 1.6 (95% CI, 0.81-3.17; P = .1) for EFS when compared with the use of KIR3DL1-weak inhibiting donors. Donor KIR2DS1/HLA-C1 status and centromeric KIR haplotype-B content were not associated with decreased risk of AML relapse. There was no benefit to KIR-based donor selection in patients with MDS. This study demonstrates that donor KIR typing is feasible, and prioritization of donors with certain KIR3DL1 genotypes may confer a protection from relapse after HCT in patients with AML. © 2021 by The American Society of Hematology.
Journal Title: Blood Advances
Volume: 5
Issue: 7
ISSN: 2473-9529
Publisher: American Society of Hematology  
Date Published: 2021-04-13
Start Page: 2003
End Page: 2011
Language: English
DOI: 10.1182/bloodadvances.2020002701
PUBMED: 33843984
PROVIDER: scopus
PMCID: PMC8045509
Notes: Article -- Export Date: 1 June 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Sergio Andres Giralt
    747 Giralt
  2. Katharine C Hsu
    163 Hsu
  3. Eric Nelson Davis
    16 Davis
  4. Sean McCarthy Devlin
    437 Devlin
  5. Deborah Sessions Wells
    23 Wells
  6. Roni Tamari
    133 Tamari
  7. Brian Carl Shaffer
    88 Shaffer
  8. Candice Jenna Cooper
    9 Cooper
  9. Beth Suri
    3 Suri
  10. Soo Park
    3 Park
  11. Anne Clay Archer
    1 Archer