Activating killer-cell immunoglobulin-like receptor haplotype influences clinical outcome following HLA-matched sibling haematopoietic stem cell transplantation

Autor:	Peter Bardy, Lucy C. Sullivan, Anthony P. Schwarer, Uwe Hahn, Charles G. Mullighan, Kathleen Doherty, Geraldine M. O’Connor, Silke Danner, Jeff Szer, Susan L. Heatley, Andrew G. Brooks, Kenneth F. Bradstock
Rok vydání:	2018
Předmět:	0301 basic medicine Donor selection business.industry Immunology Haplotype Killer-cell immunoglobulin-like receptor C550 Myeloid leukemia A100 chemical and pharmacologic phenomena Human leukocyte antigen medicine.disease Transplantation 03 medical and health sciences Haematopoiesis 030104 developmental biology 0302 clinical medicine Graft-versus-host disease Genetics medicine Immunology and Allergy business 030215 immunology
Zdroj:	HLA. 92:74-82
ISSN:	2059-2302
Popis:	Natural killer cells are thought to influence the outcome of hematopoietic stem cell transplant (HSCT), impacting on relapse, overall survival, graft versus host disease and the control of infection, in part through the complex interplay between the large and genetically diverse killer immunoglobulin-like receptor (KIR) family and their ligands. This study examined the relationship between KIR gene content and clinical outcomes including the control of opportunistic infections such as cytomegalovirus in the setting of human leucocyte antigen (HLA)-matched sibling HSCT in an Australian cohort. The presence of the KIR B haplotype which contain more activating receptors in the donor, in particular centromeric B haplotype genes (Cen-B), was associated with improved overall survival of patients with acute myeloid leukemia (AML) undergoing sibling HSCT and receiving myeloablative conditioning. Donor Cen-B haplotype was also associated with reduced acute graft versus host disease grades II-IV whereas donor telomeric-B haplotype was associated with decreased incidence of CMV reactivation. In contrast, we were not able to demonstrate a reduced rate of relapse when the donor had KIR Cen-B, however relapse with a donor Cen-A haplotype was a competing risk factor to poor overall survival. Here we show that the presence of donor activating KIR led to improved outcome for the patient, potentially through reduced relapse rates and decreased incidence of acute GvHD translating to improved overall survival. This article is protected by copyright. All rights reserved.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f9b8d691c219164a28be7e6c2275776 https://doi.org/10.1111/tan.13327 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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