Relapse protection following early CMV reactivation after HSCT is limited to HLA-C KIR ligand homozygous recipients.

Abstract

BACKGROUND\nWhile the risk for non-relapse mortality (NRM) associated with early cytomegalovirus (CMV) reactivation (CMVR) after allogeneic hematopoietic stem cell transplantation (HSCT) is well established, debate is ongoing on whether CMVR may reduce the risk of primary disease relapse.\n\n\nOBJECTIVE\nRelapse protection following early CMV reactivation after HSCT in the context of the HLA-C KIR ligands of the recipients.\n\n\nSTUDY DESIGN\nIn this retrospective, bi-centric study, 406 matched-related or unrelated transplants for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) were stratified by HLA-C KIRL groups (homozygous versus heterozygous) and were separately analyzed for the impact of early CMVR on the cumulative incidence of relapse, non-relapse mortality (NRM), acute and chronic graft-versus-host-disease (GVHD), using landmark and multi-state analyses.\n\n\nRESULTS\nBy landmark analysis of patients alive and relapse-free 45 days post-HSCT, HLA-C KIRL homozygous recipients (C1/1 or C2/2) had a lower risk of subsequent relapse if CMVR occurred before this landmark (sub-hazard ratio (sHR) 0.36; P=0.002). By contrast, in HLA-C KIRL heterozygous (C1/2) recipients, early CMVR had no impact on subsequent relapse (sHR 0.88; P=0.63). In the homozygous cohort, NRM (sHR 3.31; P<0.001), and aGVHD 3-4 (sHR 2.60; P=0.04) were significantly increased after early CMVR, but not so in the heterozygous group (sHR 1.23; P=0.53, and sHR 1.40; P=0.50). Multivariable landmark analyses and a multi-state model confirmed the limitation of the relapse-protective effect of early CMVR to the homozygous cohort. Chronic GVHD and overall survival were not influenced in neither cohort.\n\n\nCONCLUSION\nAn antileukemic effect of early CMVR after HSCT for AML/MDS was significant, but strictly limited to recipients homozygous for HLA-C KIRL. However, particularly in this cohort, CMVR had an adverse impact on aGVHD and NRM.