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Role of thymoglobulin in matched sibling allogeneic hematopoietic stem cell transplantation with busulfan and fludarabine conditioning in myeloid malignanicies

Bone Marrow Transplantation volume 53, pages 207–212 (2018)Cite this article

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Abstract

In vivo T-cell depletion using anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis of GvHD. We investigated the influence of thymoglobulin dose (an ATG) on GvHD following matched sibling donor (MSD) HSCT with a busulfan and fludarabine preparative regimen. Medical records of 180 patients who received MSD HSCT with a conditioning regimen of busulfan, fludarabine, and ATG (BuFluATG) were reviewed retrospectively. The median age was 53 years (range 18–68). Initial diagnoses were acute myeloid leukemia (73.3%) and myelodysplastic syndrome (26.7%). Forty-four and 68 patients (24.4 and 37.7%) experienced acute and chronic GvHD of any grade, respectively. High-dose (⩾4.5 mg/kg) ATG was independently associated with decreased risk of acute GvHD (hazard ratio=0.36, 95% confidence interval (CI): 0.15–0.84, P=0.019) compared to low-dose ATG (<4.5 mg/kg). Although ATG dose was associated with the risk of acute GvHD, it was not associated with the risk of chronic GvHD in our study. A higher dose (⩾4.5 mg/kg) of ATG decreases the risk of acute GvHD but had no significant impact on disease-free survival in MSD HSCT patients conditioned with BuFluATG. The optimal dose of ATG should be further investigated in a large prospective study context.

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References

  1. Tabbara IA, Zimmerman K, Morgan C, Nahleh Z . Allogeneic hematopoietic stem cell transplantation: complications and results. Arch intern med 2002; 162: 1558–1566.

    Article  Google Scholar 

  2. Chi AK, Soubani AO, White AC, Miller KB . An update on pulmonary complications of hematopoietic stem cell transplantation. Chest 2013; 144: 1913–1922.

    Article  Google Scholar 

  3. Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W et al. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood 2006; 107: 3065–3073.

    Article  CAS  Google Scholar 

  4. 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: 164–173.

    Article  CAS  Google Scholar 

  5. Devillier R, Furst S, El-Cheikh J, Castagna L, Harbi S, Granata A et al. Antithymocyte globulin in reduced-intensity conditioning regimen allows a high disease-free survival exempt of long-term chronic graft-versus-host disease. Biol blood marrow transplant 2014; 20: 370–374.

    Article  CAS  Google Scholar 

  6. Kroger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N Engl j med 2016; 374: 43–53.

    Article  Google Scholar 

  7. Ruutu T, Gratwohl A, de Witte T, Afanasyev B, Apperley J, Bacigalupo A et al. Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice. Bone marrow transplant 2014; 49: 168–173.

    Article  CAS  Google Scholar 

  8. Storek J, Mohty M, Boelens JJ . Rabbit anti-T cell globulin in allogeneic hematopoietic cell transplantation. Biol blood marrow transplant 2015; 21: 959–970.

    Article  CAS  Google Scholar 

  9. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 consensus conference on acute GVHD grading. Bone marrow transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  10. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am j med 1980; 69: 204–217.

    Article  CAS  Google Scholar 

  11. Fine JP, Gray RJ . A proportional hazards model for the subdistribution of a competing risk. J Am stat assoc 1999; 94: 496–509.

    Article  Google Scholar 

  12. Schemper M, Smith TL . A note on quantifying follow-up in studies of failure time. Control clin trials 1996; 17: 343–346.

    Article  CAS  Google Scholar 

  13. 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: 855–864.

    Article  CAS  Google Scholar 

  14. Russell JA, Turner AR, Larratt L, Chaudhry A, Morris D, Brown C et al. Adult recipients of matched related donor blood cell transplants given myeloablative regimens including pretransplant antithymocyte globulin have lower mortality related to graft-versus-host disease: a matched pair analysis. Biol blood marrow transplant 2007; 13: 299–306.

    Article  CAS  Google Scholar 

  15. Imataki O, Matsumoto K, Uemura M . Low-dose anti-thymocyte globulin reduce severe acute and chronic graft-versus-host disease after allogeneic stem cell transplantation. J cancer res clin oncol 2017; 143: 709–715.

    Article  CAS  Google Scholar 

  16. Devillier R, Furst S, Crocchiolo R, El-Cheikh J, Castagna L, Harbi S et al. A conditioning platform based on fludarabine, busulfan, and 2 days of rabbit antithymocyte globulin results in promising results in patients undergoing allogeneic transplantation from both matched and mismatched unrelated donor. Am j hematol 2014; 89: 83–87.

    Article  CAS  Google Scholar 

  17. Ji YS, Lee MS, Min CW, Park SK, Kim SH, Yun J et al. Does anti-thymocyte globulin have a place in busulfan/fludarabine conditioning for matched related donor hematopoietic stem cell transplantation? Korean j int med 2016; 31: 750–761.

    Article  CAS  Google Scholar 

  18. Devillier R, Labopin M, Chevallier P, Lioure B, Socie G, Huynh A et al. Higher doses of antithymocyte globulin (ATG) increase the risk of relapse in acute myeloid leukemia (AML) patients undergoing matched related donor allogeneic transplantation in first complete remission (CR1): an analysis from the acute leukemia working party of EBMT. Blood 2014; 124: 729–729.

    Article  Google Scholar 

  19. Crocchiolo R, Esterni B, Castagna L, Furst S, El-Cheikh J, Devillier R et al. Two days of antithymocyte globulin are associated with a reduced incidence of acute and chronic graft-versus-host disease in reduced-intensity conditioning transplantation for hematologic diseases. Cancer 2013; 119: 986–992.

    Article  CAS  Google Scholar 

  20. Busca A, Passera R, Pini M, Zallio F, Dellacasa C, Audisio E et al. The use of ATG abrogates the antileukemic effect of cytomegalovirus reactivation in patients with acute myeloid leukemia receiving grafts from unrelated donors. Am j hematol 2015; 90: E117–E121.

    Article  CAS  Google Scholar 

  21. Kim HT, Armand P . Clinical endpoints in allogeneic hematopoietic stem cell transplantation studies: the cost of freedom. Biol blood marrow transplant 2013; 19: 860–866.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea

    D-Y Shin & S-S Yoon

  2. Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    D-Y Shin & S-S Yoon

  3. Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    J-H Lee

  4. Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    S Park

  5. Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi, South Korea

    J-O Lee

  6. Department of Hematology, Kyungpook National University Hospital, Daegu, South Korea

    J-H Moon

  7. Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, South Korea

    J-S Ahn

  8. Department of Internal Medicine, Ulsan University Hospital, Ulsan, South Korea

    Y Choi

  9. Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea

    I-C Song

  10. Department of Internal Medicine, Busan National University Hospital, Busan, South Korea

    H-J Shin

  11. Department of Internal Medicine, Busan Paik Hospital, Busan, South Korea

    W S Lee

  12. Department of Internal Medicine, Kosin University Gospel Hospital, Busan, South Korea

    H S Lee

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  1. D-Y Shin
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Correspondence to H S Lee or S-S Yoon.

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Shin, DY., Lee, JH., Park, S. et al. Role of thymoglobulin in matched sibling allogeneic hematopoietic stem cell transplantation with busulfan and fludarabine conditioning in myeloid malignanicies. Bone Marrow Transplant 53, 207–212 (2018). https://doi.org/10.1038/bmt.2017.240

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  • DOI: https://doi.org/10.1038/bmt.2017.240

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