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

Journal article


Publication Details

Author(s): 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 KD, Strahm B, Wössmann W, Escherich G, Zimmermann M, Schrappe M, Borkhardt A, Eckert C, Bader P, Uhrberg M, Meisel R
Journal: Bone Marrow Transplantation
Publication year: 2019
ISSN: 1476-5365


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.


FAU Authors / FAU Editors

Stachel, Klaus Daniel PD Dr.
Medizinische Fakultät


Additional Organisation
Kinder- und Jugendklinik


External institutions with authors

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


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: 

Last updated on 2019-03-06 at 11:41