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Antithymocyte globulin for graft-versus-host disease prophylaxis: an updated systematic review and meta-analysis

Abstract

Graft-versus-host disease (GVHD) remains a limiting factor for successful allogeneic hematopoietic cell transplantation (allo-HCT). Conflicting data exist on the benefit of ATG on post-transplant survival. We performed a systematic review of randomized controlled trials (RCTs) to assess benefits and harms of thymoglobulin and Fresenius (re-branded as Grafalon) ATG formulations in patients undergoing allo-HCT for a variety of hematologic malignancies and bone marrow failure syndromes. A comprehensive search of MEDLINE, EMBASE, and Cochrane Library was performed. Data on methodological quality, benefits, and harms were extracted for each trial and pooled under a random-effects model. Eight RCTs (1134 patients) met the inclusion criteria. Methodological quality ranged from moderate to very low. Pooled results showed no difference in overall survival (OS) with the use of ATG (hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.74–1.28; P = 0.83). ATG reduced grade II/III acute GVHD (risk ratio (RR) = 0.61; 95% CI = 0.48–0.77; P < 0.0001), grade III/IV acute GVHD (RR = 0.52; 95% CI = 0.34–0.81; P = 0.004), and chronic GVHD (RR = 0.52; 95% CI = 0.40–0.69; P < 0.00001) without an increase in non-relapse mortality (NRM) (RR = 0.91; 95% CI = 0.74–1.13; P = 0.40). Future studies with better methodological quality are needed to provide conclusive answers related to optimal dosing and timing of ATG for prevention of GVHD.

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Author contributions

AK, TR, MH, MM, and MAK-D designed the study; TR performed the search of databases; MAK-D, AK, TR, MH, and MM performed the selection of studies; AK, TR, BM, and MAK-D performed the data analysis. AK, TR, MH, BM, MM, and MAK-D interpreted the data, provided input for the production of figures, and wrote the report. All authors reviewed and approved the final manuscript.

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Correspondence to Ambuj Kumar.

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MM received research support and lectures honoraria from Sanofi-Genzyme whose product is discussed in this manuscript. The remaining authors declare that they have no conflict of interest.

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Kumar, A., Reljic, T., Hamadani, M. et al. Antithymocyte globulin for graft-versus-host disease prophylaxis: an updated systematic review and meta-analysis. Bone Marrow Transplant 54, 1094–1106 (2019). https://doi.org/10.1038/s41409-018-0393-0

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