1.
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, A., Kiss, K. P., Balassa, K., Andrikovics, H., Batai, A., Szilvasi, A., Rajczy, K., Inotai, D., Torbagyi, E., et al
PloS one. 2019;14(6):e0218945
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.
2.
Sex-specific survival difference in association with HLA-DRB1*04 following allogeneic haematopoietic stem cell transplantation for lymphoid malignancies
Balassa, K., Andrikovics, H., Remenyi, P., Batai, A., Szilvasi, A., Bors, A., Kiss, K. P., Rajczy, K., Inotai, D., Torbagyi, E., et al
Human Immunology. 2017
Abstract
The role of HLA system in allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcome is unarguable. In this study we investigated association of HLA-A,-B and-DRB1 alleles with overall survival (OS) in 186 patients undergoing allo-HSCT for lymphoid malignancies. Analyses confirmed significantly better OS for HLA-DRB1*04 carriers compared with non-carriers (p=0.01). Survival benefit was confined to male patients (in multivariate analyses p=0.034, hazard ratio 0.35, 95% confidence interval 0.13-0.92), whereas in females no difference was noted (p=0.82). Furthermore, donor gender also affected outcome and transplantation from female HLA-DRB1*04 carrier donors resulted in superior survival compared with female non-carrier donors (p=0.01). Combined analyses including recipient/donor gender and HLA-DRB1*04 showed that survival of male patients varied significantly according to donor gender and HLA-DRB1*04 carriership (p=0.04) with best survival among HLA-DRB1*04 carriers transplanted from female donors. Of relevance to our results, HLA-DRB1*04 has been documented as risk allele group for lymphoid malignancies, and studies described a male-specific risk. We believe that our findings provide further supporting evidence for sex-specific alterations secondary to HLA-DRB1*04 or related genes. Further studies are warranted to evaluate whether in contrast to general favour of male donors HLA-DRB1*04 carrier patients with lymphoid malignancies could benefit from transplantation from female donors. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.