KIR2DS4 and Its Variant KIR1D in KIR-AA Genotype Donors Showed Differential Survival Impact in Patients with Lymphoid Disease after HLA-Matched Unrelated Hematopoietic Stem Cell Transplantation

被引：0

作者：

Gowdavally, Sowmya ^{[1
,2
]}

Tsamadou, Chrysanthi ^{[1
,2
]}

Platzbecker, Uwe ^{[3
]}

Sala, Elisa ^{[4
]}

Valerius, Thomas ^{[5
]}

Klein, Stefan ^{[6
]}

Kroeger, Nicolaus ^{[7
]}

Wulf, Gerald ^{[8
]}

Einsele, Hermann ^{[9
]}

Thurner, Lorenz ^{[10
]}

Schaefer-Eckart, Kerstin ^{[11
]}

Freitag, Sebastian ^{[12
]}

Casper, Jochen ^{[13
]}

Duerholt, Mareike ^{[14
]}

Kaufmann, Martin ^{[15
]}

Hertenstein, Bernd ^{[16
]}

Ringhoffer, Mark ^{[17
]}

Schmeller, Sandra ^{[18
]}

Neuchel, Christine ^{[1
,2
]}

Rode, Immanuel ^{[1
,2
]}

Amann, Elisa Maria ^{[1
,2
]}

Richter, Anita ^{[1
,2
]}

Schrezenmeier, Hubert ^{[1
,2
]}

Mytilineos, Joannis ^{[18
,19
]}

Fuerst, Daniel ^{[1
,2
,20
]}

机构：

[1] Univ Hosp Ulm, Inst Clin Transfus Med & Immunogenet Ulm, German Red Cross Blood Transfus Serv, D-89081 Ulm, Germany

[2] Univ Ulm, Inst Transfus Med, Ulm, Germany

[3] Univ Leipzig, Dept Hematol Oncol & Hemostaseol, Leipzig, Germany

[4] Univ Ulm, Dept Internal Med 3, Ulm, Germany

[5] Christian Albrechts Univ Kiel, Sect Stem Cell Transplantat & Immunotherapy, Dept Med 2, Kiel, Germany

[6] Univ Med Mannheim, Med Clin 3, Mannheim, Germany

[7] Univ Hosp Hamburg Eppendorf, Dept Stem Cell Transplantat, Hamburg, Germany

[8] Univ Med Goettingen, Hematol & Med Oncol, Gottingen, Germany

[9] Univ Hosp Wurzburg, Dept Internal Med 2, Wurzburg, Germany

[10] Univ klinikum Saarlandes, Dept Internal Med I, Homburg, Germany

[11] Nuremberg Hosp, Med Clin 5 Hematol Oncol, Nurnberg, Germany

[12] Rostock Univ, Dept Med 3, Hematol Oncol Palliat Care, Med Ctr, Rostock, Germany

[13] Univ Clin, Klinikum Oldenburg, Dept Hematol & Oncol, Oldenburg, Germany

[14] Evangel Clin Essen Werden, Hematol Oncol, Essen, Germany

[15] Robert Bosch Krankenhaus, Dept Internal Med Oncol & Hematol 2, Stuttgart, Germany

[16] Klinikum Bremen Mitte, Hematol Oncol, Bremen, Germany

[17] Stadt Klinikum Karlsruhe, Med Clin 3, Karlsruhe, Germany

[18] German Registry Stem Cell Transplantat, Ulm, Germany

[19] German Natl Bone Marrow Donor Registry, Zent Knochenmarkspender Register Deutschland, Ulm, Germany

[20] Inst Clin Transfus Med & Immunogenet Ulm, Dept Transplantat Immunol, Helmholtzstr 10, D-89081 Ulm, Germany

来源：

TRANSPLANTATION AND CELLULAR THERAPY | 2023年 / 29卷 / 07期

关键词：

KIR2DS4; KIR1D; Hematopoietic Stem Cell; tTransplantation; KIR alloreactivity; KIR-Receptor; RECEPTOR GENES; ACUTE GVHD; CLASSIFICATION; ALLOREACTIVITY; POLYMORPHISMS; EXPRESSION; HAPLOTYPES; SELECTION; LIGANDS; RELAPSE;

D O I：

10.1016/j.jtct.2023.04.006

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Previous studies have illustrated associations between the presence of activating killer cell immunoglobulin-like receptor (KIR) genes and lower susceptibility to hematologic malignancies in humans. In addition, favorable hematopoietic stem cell transplantation (HSCT) outcomes have been reported in patients who received transplants from donors with KIR genotypes dominant for activating KIR receptors. However, the association of activating KIR genes on an allelic level with disease and their impact on HSCT outcome has been little investigated to date. To this end, we genotyped a large transplantation cohort for KIR 2 Ig domains and short cytoplasmic tail 4 (KIR2DS4) polymorphisms and investigated their association with disease. We next investigated the impact of KIR-AA genotype donor KIR2DS4 polymorphisms (AA/KIR2DS4 versus AA/ KIR 1 Ig domain [KIR1D]) on clinical outcomes of HSCT in myeloid versus lymphoid patient subgroups. Among 2810 transplantation donor-recipient pairs, 68.8% (n = 1934) were 10/10 HLA-matched and 31.2% (n = 876) were 9/10 HLA-matched. The distribution of KIR1D was equal in patients and donors (P = .205). Multivariate analysis in 10/10 HLA-matched patients with lymphoid disease showed improved HSCT outcomes when they received grafts from AA/KIR1D donors (overall survival: hazard ratio [HR], .62, P = .002; disease free survival: HR, .70, P = .011; graft-versus-host disease-free and relapse-free survival: HR, .67, P = .002; nonrelapse mortality: HR, .55, P < .001). This effect was not seen in either 9/10 HLAmatched patients with lymphoid disease or patients with myeloid disease. Our study indicates that the presence of KIR1D alleles is not associated with disease in patients, and, interestingly, using grafts from AA/ KIR1D donors translated into beneficial survival outcomes in 10/10 HLA-matched patients with lymphoid disease.

引用

页码：457e1 / 457e10

页数：10

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