Impact of donor activating KIR genes on HSCT outcome in C1-ligand negative myeloid disease patients transplanted with unrelated donors - A retrospective study

Neuchel C, Fuerst D, Niederwieser D, Bunjes D, Tsamadou C, Wulf G, Pfreundschuh M, Wagner E, Stuhler G, Einsele H, Schrezenmeier H, Mytilineos J (2017)

Publication Type: Journal article

Publication year: 2017

Journal

PLoS ONE Public Library of Science

Book Volume: 12

Article Number: e0169512

Journal Issue: 1

DOI: 10.1371/journal.pone.0169512

Abstract

Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immu-noglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: HR = 1.41, CI = 1.14-1.74, p = 0.0012), disease free survival (DFS: HR = 1.27, CI = 1.05-1.53, p = 0.015), treatment related mortality (TRM: HR = 1.41, CI = 1.01-1.96, p = 0.04), and relapse incidence (RI: HR = 1.33, CI = 1.01-1.75, p = 0.04) all being inferior when compared to C1-positive patients (n = 1246). Subsequent analysis showed that these findings applied for patients with myeloid malignancies but not for patients with lymphoproliferative diseases (OS: myeloid: HR = 1.51, CI = 1.15-1.99, p = 0.003; lymphoblastic: HR = 1.26, CI = 0.91-1.75, p = 0.16; DFS: myeloid: HR = 1.31, CI = 1.01-1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90-1.61, p = 0.21; RI: myeloid: HR = 1.31, CI = 1.01-1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90-1.61, p = 0.21). Interestingly, within the C1-negative patient group, transplantation with KIR2DS2 resulted in better OS (9/10 matched: HR = 0.24, CI = 0.08-0.67, p = 0.007) as well as DFS (9/10 matched: HR = 0,26, CI = 0.11-0.60, p = 0.002), and transplantation with KIR2DS1 positive donors was associated with a decreased RI (HR = 0.30, CI = 0.13-0.69, p = 0.005). TRM was increased when the donor was positive for KIR2DS1 (HR = 2.61, CI = 1.26-5.41, p = 0.001). Our findings suggest that inclusion of KIR2DS1/2/5 and KIR3DS1-genotyping in the unrelated donor search algorithm of C1-ligand negative patients with myeloid malignancies may prove to be of clinical relevance.

Involved external institutions

DRK-Blutspendedienst Baden-Württemberg - Hessen / German Red Cross Blood Donor Service Baden-Wuerttemberg – Hessen DE Germany (DE) Universität Leipzig DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Georg-August-Universität Göttingen DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Deutsche Klinik für Diagnostik DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE)

How to cite

APA:

Neuchel, C., Fuerst, D., Niederwieser, D., Bunjes, D., Tsamadou, C., Wulf, G.,... Mytilineos, J. (2017). Impact of donor activating KIR genes on HSCT outcome in C1-ligand negative myeloid disease patients transplanted with unrelated donors - A retrospective study. PLoS ONE, 12(1). https://doi.org/10.1371/journal.pone.0169512

MLA:

Neuchel, Christine, et al. "Impact of donor activating KIR genes on HSCT outcome in C1-ligand negative myeloid disease patients transplanted with unrelated donors - A retrospective study." PLoS ONE 12.1 (2017).

BibTeX: Download