Presence of centromeric but absence of telomeric group B KIR haplotypes in stem cell donors improve leukaemia control after HSCT for childhood ALL

Babor F, Peters C, Manser AR, Glogova E, Sauer M, Pötschger U, Ahlmann M, Cario G, Feuchtinger T, Gruhn B, Güngör T, Horn PA, Kremens B, Lang P, Mezger M, Müller I, Mytilineos J, Oevermann L, Pichler H, Scherenschlich N, Schuster FR, Siepermann M, Stachel D, Strahm B, Wössmann W, Escherich G, Zimmermann M, Schrappe M, Borkhardt A, Eckert C, Bader P, Uhrberg M, Meisel R (2019)

Publication Type: Journal article

Publication year: 2019

Journal

DOI: 10.1038/s41409-019-0543-z

Abstract

Although allogeneic hematopoietic stem-cell transplantation (HSCT) provides high cure rates for children with high-risk acute lymphoblastic leukaemia (ALL), relapses remain the main cause of treatment failure. Whereas donor killer cell immunoglobulin-like receptor (KIR) genotype was shown to impact on relapse incidence in adult myeloid leukaemia similar studies in paediatric ALL are largely missing. Effect of donor KIR genotype on transplant outcome was evaluated in 317 children receiving a first myeloablative HSCT from an HLA-matched unrelated donor or sibling within the prospective ALL-SCT-BFM-2003 trial. Analysis of donor KIR gene polymorphism revealed that centromeric presence and telomeric absence of KIR B haplotypes was associated with reduced relapse risk. A centromeric/telomeric KIR score (ct-KIR score) integrating these observations correlated with relapse risk (hazard ratio (HR) 0.58; P = 0.002) while it had no impact on graft-versus-host disease or non-relapse mortality. In multivariable analyses ct-KIR score was associated with reduced relapse risk (HR 0.58; P = 0.003) and a trend towards improved event-free survival (HR 0.76; P = 0.059). This effect proved independent of MRD level prior to HSCT. Our data suggest that in children with ALL undergoing HSCT after myeloablative conditioning, donor selection based on KIR genotyping holds promise to improve clinical outcome by decreasing relapse risk and prolonged event-free survival.

Authors with CRIS profile

Additional Organisation(s)

Involved external institutions

Universitätsklinikum Jena Germany (DE) Justus-Liebig-Universität Gießen Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Essen Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Klinikum der Universität München Germany (DE) Universitätsklinikum Ulm Germany (DE) Universitätsklinikum Tübingen Germany (DE) Medizinische Universität Wien Austria (AT) Charité - Universitätsmedizin Berlin Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Münster Germany (DE) Universitäts-Kinderspital Zürich Switzerland (CH)

How to cite

APA:

Babor, F., Peters, C., Manser, A.R., Glogova, E., Sauer, M., Pötschger, U.,... Meisel, R. (2019). Presence of centromeric but absence of telomeric group B KIR haplotypes in stem cell donors improve leukaemia control after HSCT for childhood ALL. Bone Marrow Transplantation. https://dx.doi.org/10.1038/s41409-019-0543-z

MLA:

Babor, Florian, et al. "Presence of centromeric but absence of telomeric group B KIR haplotypes in stem cell donors improve leukaemia control after HSCT for childhood ALL." Bone Marrow Transplantation (2019).

BibTeX: Download