Next Article in Journal
Glycosylated Triterpenoids as Endosomal Escape Enhancers in Targeted Tumor Therapies
Next Article in Special Issue
Advances in the Use of Regulatory T-Cells for the Prevention and Therapy of Graft-vs.-Host Disease
Previous Article in Journal
Novel Computerized Method for Measurement of Retinal Vessel Diameters
Article Menu
Issue 2 (June) cover image

Export Article

Open AccessArticle
Biomedicines 2017, 5(2), 13; doi:10.3390/biomedicines5020013

HLA-C KIR-Ligands Determine the Impact of Anti-Thymocyte Globulin (ATG) on Graft versus Host and Graft versus Leukemia Effects Following Hematopoietic Stem Cell Transplantation

1
Department of Hematology and Oncology, Elisabethinen Hospital, 4020 Linz, Austria
2
Department of Hematology and Oncology, Medical University, 6020 Innsbruck, Austria
3
Austrian Red Cross, Transfusion Service for Upper Austria, 4020 Linz, Austria
*
Author to whom correspondence should be addressed.
Academic Editors: Antonio Di Stasi and Ayman Saad
Received: 27 February 2017 / Revised: 15 March 2017 / Accepted: 23 March 2017 / Published: 28 March 2017
(This article belongs to the Special Issue Cell Therapy for the Treatment of GVHD)
View Full-Text   |   Download PDF [902 KB, uploaded 28 March 2017]   |  

Abstract

Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD. Congruously, we have previously reported favorable outcomes in C1/1 recipients after ATG-based transplants in a monocentric analysis. Here, within an extended cohort, we test the hypothesis that incorporation of ATG for GVHD prophylaxis may improve survival particularly in HSCT recipients with at least one C1 KIR-ligand. Retrospectively, 775 consecutive allogeneic (excluding haploidentical) HSCTs were analyzed, including peripheral blood and bone marrow grafts for adults with hematological diseases at two Austrian HSCT centers. ATG-Fresenius/Grafalon, Thymoglobuline, and alemtuzumab were applied in 256, 87, and 7 transplants, respectively (subsequently summarized as “ATG”), while 425 HSCT were performed without ATG. Median follow-up of surviving patients is 48 months. Adjusted for age, disease-risk, HLA-match, donor and graft type, sex match, cytomegalovirus serostatus, conditioning intensity, and type of post-grafting GVHD prophylaxis, Cox regression analysis of the entire cohort (n = 775) revealed a significant association of ATG with decreased non-relapse mortality (NRM) (risk ratio (RR), 0.57; p = 0.001), and overall mortality (RR, 0.71; p = 0.014). Upon stratification for HLA-C KIR-L, the greatest benefit for ATG emerged in C1/1 recipients (n = 291), by reduction of non-relapse (RR, 0.34; p = 0.0002) and overall mortality (RR, 0.50; p = 0.003). Less pronounced, ATG decreased NRM (RR, 0.60; p = 0.036) in HLA-C group 1/2 recipients (n = 364), without significantly influencing overall mortality (RR, 0.70; p = 0.065). After exclusion of higher-dose ATG-based transplants, serotherapy significantly improved both NRM (RR, 0.54; p = 0.019; n = 322) and overall mortality (RR, 0.60; p = 0.018) in C1/2 recipients as well. In both, C1/1 (RR, 1.70; p = 0.10) and particularly in C1/2 recipients (RR, 0.94; p = 0.81), there was no statistically significant impact of ATG on relapse incidence. By contrast, in C2/2 recipients (n = 121), ATG neither reduced NRM (RR, 1.10; p = 0.82) nor overall mortality (RR, 1.50; p = 0.17), but increased the risk for relapse (RR, 4.38; p = 0.02). These retrospective findings suggest ATG may provide a survival benefit in recipients with at least one C1 group KIR-L, by reducing NRM without significantly increasing the relapse risk. View Full-Text
Keywords: hematopoietic stem cell transplantation; serotherapy; antithymocyte globulin; graft-versus-host disease; HLA-C; killer cell immunoglobulin-like receptor; KIR ligand hematopoietic stem cell transplantation; serotherapy; antithymocyte globulin; graft-versus-host disease; HLA-C; killer cell immunoglobulin-like receptor; KIR ligand
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Clausen, J.; Böhm, A.; Straßl, I.; Stiefel, O.; Buxhofer-Ausch, V.; Machherndl-Spandl, S.; König, J.; Schmidt, S.; Steitzer, H.; Danzer, M.; Kasparu, H.; Weltermann, A.; Nachbaur, D. HLA-C KIR-Ligands Determine the Impact of Anti-Thymocyte Globulin (ATG) on Graft versus Host and Graft versus Leukemia Effects Following Hematopoietic Stem Cell Transplantation. Biomedicines 2017, 5, 13.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomedicines EISSN 2227-9059 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top