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

被引：19

作者：

Babor, Florian ^{[1
]}

Peters, Christina ^{[2
]}

Manser, Angela R. ^{[3
]}

Glogova, Evgenia ^{[2
]}

Sauer, Martin ^{[4
]}

Poetschger, Ulrike ^{[2
]}

Ahlmann, Martina ^{[5
]}

Cario, Gunnar ^{[6
]}

Feuchtinger, Tobias ^{[7
]}

Gruhn, Bernd ^{[8
]}

Gungor, Tayfun ^{[9
]}

Horn, Peter A. ^{[10
,12
]}

Kremens, Bernhard ^{[11
,12
]}

Lang, Peter

Mezger, Markus ^{[12
]}

Mueller, Ingo ^{[13
]}

Mytilineos, Joannis ^{[14
]}

Oevermann, Lena ^{[15
]}

Pichler, Herbert ^{[2
]}

Scherenschlich, Nadine ^{[1
,3
]}

Schuster, Friedhelm R. ^{[1
]}

Siepermann, Meinolf ^{[3
]}

Stachel, Daniel ^{[16
]}

Strahm, Brigitte ^{[17
]}

Woessmann, Wilhelm ^{[18
]}

Escherich, Gabriele ^{[13
]}

Zimmermann, Martin ^{[4
]}

Schrappe, Martin ^{[6
]}

Borkhardt, Arndt ^{[19
]}

Eckert, Cornelia ^{[15
]}

Bader, Peter ^{[20
]}

Uhrberg, Markus ^{[3
]}

Meisel, Roland ^{[1
]}

机构：

[1] Heinrich Heine Univ, Ctr Child & Adolescent Hlth, Clin Pediat Oncol Hematol & Clin Immunol, Div Pediat Stem Cell Therapy, Dusseldorf, Germany

[2] Med Univ Vienna, St Anna Childrens Hosp, Dept Paediat, Vienna, Austria

[3] Heinrich Heine Univ, Inst Transplantat Diagnost & Cell Therapeut, Dusseldorf, Germany

[4] Hannover Med Sch, Dept Pediat Hematol Oncol & Blood Stem Cell Trans, Hannover, Germany

[5] Univ Childrens Hosp Munster, Dept Pediat Hematol & Oncol, Munster, Germany

[6] Univ Med Ctr Schleswig Holstein, Dept Pediat, Campus Kiel, Kiel, Germany

[7] Ludwig Maximilians Univ Munchen, Dr von Haunersches Kinderspital, Pediat Hematol Oncol & Stem Cell Transplantat, Munich, Germany

[8] Jena Univ Hosp, Dept Pediat, Jena, Germany

[9] Univ Childrens Hosp, Dept Pediat, Div Stem Cell Transplantat, Zurich, Switzerland

[10] Univ Hosp, Inst Transfus Med, Essen, Germany

[11] Univ Hosp, Dept Paediat 3, Essen, Germany

[12] Univ Tubingen, Childrens Hosp, Tubingen, Germany

[13] Univ Med Ctr Hamburg Eppendorf, Div Pediat Stem Cell Transplantat & Immunol, Hamburg, Germany

[14] Inst Clin Transfus Med & Immunogenet, Ulm, Germany

[15] Charite Univ Med Berlin, Dept Pediat Oncol Hematol, Berlin, Germany

[16] Univ Erlangen Nurnberg, Childrens Hosp, Dept Pediat Hematol & Oncol, Erlangen, Germany

[17] Univ Childrens Hosp Freiburg, Div Pediat Hematol & Oncol, Freiburg, Germany

[18] Justus Liebig Univ, Dept Pediat Hematol & Oncol, Giessen, Germany

[19] Heinrich Heine Univ, Med Fac, Ctr Child & Adolescent Hlth, Clin Pediat Oncol Hematol & Clin Immunol, Dusseldorf, Germany

[20] Goethe Univ Frankfurt, Childrens Hosp, Dept Pediat Stem Cell Transplantat & Immunol, Frankfurt, Germany

来源：

BONE MARROW TRANSPLANTATION | 2019年 / 54卷 / 11期

关键词：

ACUTE LYMPHOBLASTIC-LEUKEMIA; FREE SURVIVAL; UNRELATED TRANSPLANTATION; RELAPSE; DISEASE; GENES; DIVERSITY; INTENSITY; MORTALITY; CHILDREN;

D O I：

10.1038/s41409-019-0543-z

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

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-versushost 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.

引用

页码：1847 / 1858

页数：12

共 40 条

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