Donor KIR2DS1 reduces the risk of transplant related mortality in HLA-C2 positive young recipients with hematological malignancies treated by myeloablative conditioning

PLoS One. 2019 Jun 25;14(6):e0218945. doi: 10.1371/journal.pone.0218945. eCollection 2019.

Abstract

Background: Recognition of HLA-C2 group alleles on recipient cells by activating killer immunoglobulin like receptors, KIR2DS1 on donor natural killer cells may lead to increased graft-versus-leukemia effect or immunomodulation in patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) influencing disease free and overall survival (OS).

Objective: In the present study, 314 consecutive, allo-HSCT recipient and donor pairs were included with retrospective donor KIR-genotyping and clinical parameters analyzes.

Results: After a median follow-up of 23.6 months, recipients with HLA-C2 group allele (rC2) showed improved (p = 0.046) OS if transplanted with KIR2DS1 positive donors (d2DS1) compared to those without one or both of this genetic attribute. Within the myeloablative conditioning (MAC) subgroup (n = 227), rC2 homozygous+d2DS1 patients (n = 14) showed a 5 years OS of 93% followed by rC2 heterozygous+d2DS1 patients (n = 48, 65%) compared to rC2 and/or d2DS1 negatives (47%, p = 0.018). Multivariate analyses indicated rC2+d2DS1 positivity as an independent predictor of OS (HR:0.47, 0.26-0.86, p = 0.014) besides donor type, presence of CMV-reactivation or chemoresistant disease. Among MAC-treated patients, the combined rC2+d2DS1 presence was associated with a markedly decreased cumulative incidence of transplant related mortality (p = 0.0045).

Conclusion: The combination of rC2+d2DS1 may be a favorable genetic constellation in allo-HSCT with MAC potentially reducing transplant related mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Donors*
  • Female
  • HLA-C Antigens / genetics*
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Male
  • Middle Aged
  • Receptors, KIR / drug effects*
  • Retrospective Studies
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • HLA-C Antigens
  • KIR2DS1 protein, human
  • Receptors, KIR

Grants and funding

This work was supported by a grant from OTKA (Országos Tudományos Kutatási Alap, K104903), and by a grant called FIKP (Felsőoktatási Intézményi Kiválósági Pályázat) to AT. ABo and AH are recipients of the “Bolyai Scholarship” from MTA (Magyar Tudományos Akadémia). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.