Antithymocyte globulin improves GVHD-free and relapse-free survival in unrelated hematopoietic stem cell transplantation


Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent graft-versus-host disease (GVHD) in unrelated hematopoietic stem cell transplantation (HSCT), but the optimal dose of ATG remains unknown. We prospectively analyzed 205 unrelated HSCTs in patients with malignant hematological disorders. HSCTs were classified as follows: HLA-matched transplant without ATG (n = 53, group A), HLA-mismatched transplant treated with 6.0 mg/kg thymoglobulin (n = 77, group B), and HLA-matched transplant treated with 4.5 mg/kg thymoglobulin (n = 75, group C). For groups A and B, the 5-year moderate/severe chronic GVHD rates were 31.9% and 24.2%, the 5-year GVHD-free and relapse-free survival (GRFS) rates were 28.3 and 47%, and the 2-year immunosuppressive therapy (IST)-free survival rates were 8.6% and 40.2% (p = 0.0016), respectively. Furthermore, group C had lower incidences of grade II-IV acute GVHD (18.7%) and 5-year moderate/severe chronic GVHD (16.6%) than group A did. Group C had higher 5-year GRFS (52.1% vs 28.3%, p = 0.002), 2-year IST-free survival (51.7% vs 8.6%, p = 0.00004), and 5-year overall survival (OS) (68.3% vs 41.5%, p = 0.007) rates than group A did. Thus, ATG was associated with better GVHD prevention, a higher rate of IST-free survival, lower transplant-related mortality (TRM), and superior OS and GRFS in unrelated HSCTs.

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  1. 1.

    Jagasia M, Arora M, Flowers ME, Chao NJ, McCarthy PL, Cutler CS, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012;119:296–307.

  2. 2.

    Morishima S, Shiina T, Suzuki S, Ogawa S, Sato-Otsubo A, Kashiwase K, et al. Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation. Blood. 2018;131:808–17.

  3. 3.

    Carapito R, Jung N, Kwemou M, Untrau M, Michel S, Pichot A, et al. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD. Blood. 2016;128:1979–86.

  4. 4.

    Crocchiolo R, Ciceri F, Fleischhauer K, Oneto R, Bruno B, Pollichieni S, et al. HLA matching affects clinical outcome of adult patients undergoing haematopoietic SCT from unrelated donors: a study from the gruppo italiano trapianto di midollo osseo and Italian bone marrow donor registry. Bone Marrow Transplant. 2009;44:571–7.

  5. 5.

    Furst D, Muller C, Vucinic V, Bunjes D, Herr W, Gramatzki M, et al. High-resolution HLA matching in hematopoietic stem cell transplantation: a retrospective collaborative analysis. Blood. 2013;122:3220–9.

  6. 6.

    Czerw T, Labopin M, Giebel S, Socie G, Volin L, Fegueux N, et al. Anti-thymocyte globulin improves survival free from relapse and graft-versus-host disease after allogeneic peripheral blood stem cell transplantation in patients with Philadelphia-negative acute lymphoblastic leukemia: an analysis by the acute leukemia working party of the EBMT. Cancer. 2018;124:2523–33.

  7. 7.

    Kharfan-Dabaja MA, Parody R, Perkins J, Lopez-Godino O, Lopez-Corral L, Vazquez L, et al. Tacrolimus plus sirolimus with or without ATG as GVHD prophylaxis in HLA-mismatched unrelated donor allogeneic stem cell transplantation. Bone Marrow Transplant. 2017;52:438–44.

  8. 8.

    Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10:855–64.

  9. 9.

    Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, et al. Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant. 2006;12:560–5.

  10. 10.

    Pidala J, Tomblyn M, Nishihori T, Ayala E, Field T, Fernandez H, et al. ATG prevents severe acute graft-versus-host disease in mismatched unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17:1237–44.

  11. 11.

    Zhu X, Lai X, Luo Y, Shi J, Tan Y, Zheng W, et al. Combination of low-dose mycophenolate mofetil with cyclosporine and methotrexate as GVHD prophylaxis in unrelated donor allogeneic stem cell transplantation. Leuk Res. 2013;37:1046–51.

  12. 12.

    Luo Y, Xiao H, Lai X, Shi J, Tan Y, He J, et al. T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin compared with matched sibling HSCT and unrelated HSCT. Blood. 2014;124:2735–43.

  13. 13.

    Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.

  14. 14.

    Chang YJ, Wang Y, Mo XD, Zhang XH, Xu LP, Yan CH, et al. Optimal dose of rabbit thymoglobulin in conditioning regimens for unmanipulated, haploidentical, hematopoietic stem cell transplantation: long-term outcomes of a prospective randomized trial. Cancer. 2017;123:2881–92.

  15. 15.

    Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, et al. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016;17:164–73.

  16. 16.

    Soiffer RJ, Kim HT, McGuirk J, Horwitz ME, Johnston L, Patnaik MM, et al. Prospective, randomized, double-blind, phase iii clinical trial of anti-T-lymphocyte globulin to assess impact on chronic graft-versus-host disease-free survival in patients undergoing HLA-matched unrelated myeloablative hematopoietic cell transplantation. J Clin Oncol. 2017;35:4003–11.

  17. 17.

    Socie G, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood. 2011;117:6375–82.

  18. 18.

    Bryant A, Mallick R, Huebsch L, Allan D, Atkins H, Anstee G, et al. Low-dose antithymocyte globulin for graft-versus-host-disease prophylaxis in matched unrelated allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23:2096–101.

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This work was supported by the National Natural Science Foundation of China (NSFC; 81730008), the National Natural Science Foundation of China (NSFC; 81670169), and the Zhejiang Key Research and Development Program (2015C03038). The funders did not influence how the research was conducted or the approval of the manuscript. We thank all patients and transplantation staff.

Author information

HH and YL designed the study. YL and MJ collected, analyzed data, performed statistical analysis, and wrote the manuscript. HH, YL, MJ, YT, YZ, JS, YZ, WZ, XL, and JY contributed to patient care and read and approved the manuscript.

Correspondence to He Huang.

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