Presence of centromeric but absence of telomeric group B KIR haplotypes in stem cell donors improve leukaemia control after HSCT for childhood ALL.
Adolescent
Adult
Child
Child, Preschool
Disease-Free Survival
Donor Selection
Female
Haplotypes
Hematopoietic Stem Cell Transplantation
Humans
Infant
Leukemia, Myeloid, Acute
/ genetics
Male
Polymorphism, Genetic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ genetics
Receptors, KIR
/ genetics
Survival Rate
Telomere
/ genetics
Transplantation Conditioning
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
07
01
2019
accepted:
04
04
2019
revised:
04
04
2019
pubmed:
16
5
2019
medline:
18
9
2020
entrez:
16
5
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31089287
doi: 10.1038/s41409-019-0543-z
pii: 10.1038/s41409-019-0543-z
doi:
Substances chimiques
Receptors, KIR
0
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1847-1858Références
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