Donor KIR2DS1 reduces the risk of transplant related mortality in HLA-C2 positive young recipients with hematological malignancies treated by myeloablative conditioning

A. Tordai, Andras Bors, Katalin Piroska Kiss, Katalin Balassa, H. Andrikovics, Arpad Batai, Aniko Szilvasi, K. Rajczy, Dora Inotai, Eva Torbagyi, Lilla Lengyel, Aniko Barta, Peter Remenyi, T. Masszi

Research output: Contribution to journalArticle

Abstract

Background Recognition of HLA-C2 group alleles on recipient cells by activating killer immunoglobulin like receptors, KIR2DS1 on donor natural killer cells may lead to increased graft-versus-leukemia effect or immunomodulation in patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) influencing disease free and overall survival (OS). Objective In the present study, 314 consecutive, allo-HSCT recipient and donor pairs were included with retrospective donor KIR-genotyping and clinical parameters analyzes. Results After a median follow-up of 23.6 months, recipients with HLA-C2 group allele (rC2) showed improved (p = 0.046) OS if transplanted with KIR2DS1 positive donors (d2DS1) compared to those without one or both of this genetic attribute. Within the myeloablative conditioning (MAC) subgroup (n = 227), rC2 homozygous+d2DS1 patients (n = 14) showed a 5 years OS of 93% followed by rC2 heterozygous+d2DS1 patients (n = 48, 65%) compared to rC2 and/ or d2DS1 negatives (47%, p = 0.018). Multivariate analyses indicated rC2+d2DS1 positivity as an independent predictor of OS (HR:0.47, 0.26–0.86, p = 0.014) besides donor type, presence of CMV-reactivation or chemoresistant disease. Among MAC-treated patients, the combined rC2+d2DS1 presence was associated with a markedly decreased cumulative incidence of transplant related mortality (p = 0.0045). Conclusion The combination of rC2+d2DS1 may be a favorable genetic constellation in allo-HSCT with MAC potentially reducing transplant related mortality.

Original languageEnglish
Article numbere0218945
JournalPloS one
Volume14
Issue number6
DOIs
Publication statusPublished - Jan 1 2019

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Transplants
Hematologic Neoplasms
Stem cells
cell transplantation
Tissue Donors
Hematopoietic Stem Cell Transplantation
Mortality
KIR Receptors
Survival
alleles
Grafts
immunomodulation
Alleles
natural killer cells
leukemia
Immunomodulation
immunoglobulins
genotyping
Natural Killer Cells
Disease-Free Survival

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Donor KIR2DS1 reduces the risk of transplant related mortality in HLA-C2 positive young recipients with hematological malignancies treated by myeloablative conditioning. / Tordai, A.; Bors, Andras; Kiss, Katalin Piroska; Balassa, Katalin; Andrikovics, H.; Batai, Arpad; Szilvasi, Aniko; Rajczy, K.; Inotai, Dora; Torbagyi, Eva; Lengyel, Lilla; Barta, Aniko; Remenyi, Peter; Masszi, T.

In: PloS one, Vol. 14, No. 6, e0218945, 01.01.2019.

Research output: Contribution to journalArticle

Tordai, A. ; Bors, Andras ; Kiss, Katalin Piroska ; Balassa, Katalin ; Andrikovics, H. ; Batai, Arpad ; Szilvasi, Aniko ; Rajczy, K. ; Inotai, Dora ; Torbagyi, Eva ; Lengyel, Lilla ; Barta, Aniko ; Remenyi, Peter ; Masszi, T. / Donor KIR2DS1 reduces the risk of transplant related mortality in HLA-C2 positive young recipients with hematological malignancies treated by myeloablative conditioning. In: PloS one. 2019 ; Vol. 14, No. 6.
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abstract = "Background Recognition of HLA-C2 group alleles on recipient cells by activating killer immunoglobulin like receptors, KIR2DS1 on donor natural killer cells may lead to increased graft-versus-leukemia effect or immunomodulation in patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) influencing disease free and overall survival (OS). Objective In the present study, 314 consecutive, allo-HSCT recipient and donor pairs were included with retrospective donor KIR-genotyping and clinical parameters analyzes. Results After a median follow-up of 23.6 months, recipients with HLA-C2 group allele (rC2) showed improved (p = 0.046) OS if transplanted with KIR2DS1 positive donors (d2DS1) compared to those without one or both of this genetic attribute. Within the myeloablative conditioning (MAC) subgroup (n = 227), rC2 homozygous+d2DS1 patients (n = 14) showed a 5 years OS of 93{\%} followed by rC2 heterozygous+d2DS1 patients (n = 48, 65{\%}) compared to rC2 and/ or d2DS1 negatives (47{\%}, p = 0.018). Multivariate analyses indicated rC2+d2DS1 positivity as an independent predictor of OS (HR:0.47, 0.26–0.86, p = 0.014) besides donor type, presence of CMV-reactivation or chemoresistant disease. Among MAC-treated patients, the combined rC2+d2DS1 presence was associated with a markedly decreased cumulative incidence of transplant related mortality (p = 0.0045). Conclusion The combination of rC2+d2DS1 may be a favorable genetic constellation in allo-HSCT with MAC potentially reducing transplant related mortality.",
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T1 - Donor KIR2DS1 reduces the risk of transplant related mortality in HLA-C2 positive young recipients with hematological malignancies treated by myeloablative conditioning

AU - Tordai, A.

AU - Bors, Andras

AU - Kiss, Katalin Piroska

AU - Balassa, Katalin

AU - Andrikovics, H.

AU - Batai, Arpad

AU - Szilvasi, Aniko

AU - Rajczy, K.

AU - Inotai, Dora

AU - Torbagyi, Eva

AU - Lengyel, Lilla

AU - Barta, Aniko

AU - Remenyi, Peter

AU - Masszi, T.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background Recognition of HLA-C2 group alleles on recipient cells by activating killer immunoglobulin like receptors, KIR2DS1 on donor natural killer cells may lead to increased graft-versus-leukemia effect or immunomodulation in patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) influencing disease free and overall survival (OS). Objective In the present study, 314 consecutive, allo-HSCT recipient and donor pairs were included with retrospective donor KIR-genotyping and clinical parameters analyzes. Results After a median follow-up of 23.6 months, recipients with HLA-C2 group allele (rC2) showed improved (p = 0.046) OS if transplanted with KIR2DS1 positive donors (d2DS1) compared to those without one or both of this genetic attribute. Within the myeloablative conditioning (MAC) subgroup (n = 227), rC2 homozygous+d2DS1 patients (n = 14) showed a 5 years OS of 93% followed by rC2 heterozygous+d2DS1 patients (n = 48, 65%) compared to rC2 and/ or d2DS1 negatives (47%, p = 0.018). Multivariate analyses indicated rC2+d2DS1 positivity as an independent predictor of OS (HR:0.47, 0.26–0.86, p = 0.014) besides donor type, presence of CMV-reactivation or chemoresistant disease. Among MAC-treated patients, the combined rC2+d2DS1 presence was associated with a markedly decreased cumulative incidence of transplant related mortality (p = 0.0045). Conclusion The combination of rC2+d2DS1 may be a favorable genetic constellation in allo-HSCT with MAC potentially reducing transplant related mortality.

AB - Background Recognition of HLA-C2 group alleles on recipient cells by activating killer immunoglobulin like receptors, KIR2DS1 on donor natural killer cells may lead to increased graft-versus-leukemia effect or immunomodulation in patients treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) influencing disease free and overall survival (OS). Objective In the present study, 314 consecutive, allo-HSCT recipient and donor pairs were included with retrospective donor KIR-genotyping and clinical parameters analyzes. Results After a median follow-up of 23.6 months, recipients with HLA-C2 group allele (rC2) showed improved (p = 0.046) OS if transplanted with KIR2DS1 positive donors (d2DS1) compared to those without one or both of this genetic attribute. Within the myeloablative conditioning (MAC) subgroup (n = 227), rC2 homozygous+d2DS1 patients (n = 14) showed a 5 years OS of 93% followed by rC2 heterozygous+d2DS1 patients (n = 48, 65%) compared to rC2 and/ or d2DS1 negatives (47%, p = 0.018). Multivariate analyses indicated rC2+d2DS1 positivity as an independent predictor of OS (HR:0.47, 0.26–0.86, p = 0.014) besides donor type, presence of CMV-reactivation or chemoresistant disease. Among MAC-treated patients, the combined rC2+d2DS1 presence was associated with a markedly decreased cumulative incidence of transplant related mortality (p = 0.0045). Conclusion The combination of rC2+d2DS1 may be a favorable genetic constellation in allo-HSCT with MAC potentially reducing transplant related mortality.

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