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Beneficial Role of Low-Dose Antithymocyte Globulin in Unrelated Stem Cell Transplantation for Adult Patients with Acquired Severe Aplastic Anemia: Reduction of Graft-versus-Host Disease and Improvement of Graft-versus-Host Disease-Free, Failure-Free Survival Rate.
Biol Blood Marrow Transplant. 2017 Sep; 23(9):1498-1508.BB

Abstract

Stem cell transplantation (SCT) from an unrelated donor (URD) is often considered in patients with severe aplastic anemia (SAA) whom immunosuppressive therapy failed and matched sibling donor is not available. To reduce the incidence of graft-versus-host disease (GVHD) in URD SCT, introducting antithymocyte globulin (ATG) into the conditioning regimen has been proposed. Although ATG was shown to play a role in reducing GVHD in a cohort with diverse hematologic diseases, its role in SAA remains uncertain. The aim of this study was to determine the efficacy and toxicity of ATG in URD SCT for adult patients with SAA. We investigated 83 adult patients with SAA who underwent URD SCT between 2003 and 2014. The transplantation strategy consisted of total body irradiation (total 800 cGy) and cyclophosphamide (total 100 mg/kg to 120 mg/kg), followed by tacrolimus and a short-term methotrexate. We divided patients into 2 groups: group 1 (n = 25), which received HLA-matched (8/8) bone marrow (BM) without ATG, and group 2 (n = 58), which received SCT from either an HLA-mismatched donor or peripheral blood (PB). Thereafter, group 2 was subdivided according to ATG use into group 2A (without ATG, n = 26), which served as a historical cohort, and group 2B (with ATG, n = 32). Rabbit ATG (Thymoglobulin; Genzyme-Sanofi, Lyon, France) was used in group 2B at a dose of 2.5 mg/kg. The median age of all patients was 30 years (range, 17 to 59 years). The incidence of GVHD was significantly lower in group 2B than group 2A, as demonstrated by the rate of grade II to IV acute GVHD at day 100 (31.2% versus 61.5%, P = .003) and the rate of chronic GVHD at 3 years (21.9% versus 65.4%, P = .002). The overall survival rates of the 3 groups were similar. However, GVHD-free, failure-free survival (GFFS) was significantly higher in group 2B than group 2A (P = .034). A multivariable model identified use of ATG as an independent factor affecting grades II to IV acute GVHD (hazard ratio [HR], 2.902; 95% confidence interval [CI], 1.417 to 5.942; P = .004), chronic GVHD (HR , 3.005; 95% CI, 1.279 to 7.059; P = .012), and GFFS (HR, 2.363; 95% CI, 1.162 to 4.805; P = .014). Toxicities, including infectious complications, were not different among the 3 groups. In conclusion, low-dose ATG (2.5 mg/kg) can reduce the incidence of acute and chronic GVHD and improve the quality of life in patients with SAA who receive stem cells from either an HLA-mismatched donor or PB; importantly, these benefits are achieved without increased toxicity. Furthermore, ATG can be considered in URD SCT from HLA-matched BM cells.

Authors+Show Affiliations

Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: jwlee@catholic.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28554856

Citation

Park, Sung-Soo, et al. "Beneficial Role of Low-Dose Antithymocyte Globulin in Unrelated Stem Cell Transplantation for Adult Patients With Acquired Severe Aplastic Anemia: Reduction of Graft-versus-Host Disease and Improvement of Graft-versus-Host Disease-Free, Failure-Free Survival Rate." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 23, no. 9, 2017, pp. 1498-1508.
Park SS, Kwak DH, Jeon YW, et al. Beneficial Role of Low-Dose Antithymocyte Globulin in Unrelated Stem Cell Transplantation for Adult Patients with Acquired Severe Aplastic Anemia: Reduction of Graft-versus-Host Disease and Improvement of Graft-versus-Host Disease-Free, Failure-Free Survival Rate. Biol Blood Marrow Transplant. 2017;23(9):1498-1508.
Park, S. S., Kwak, D. H., Jeon, Y. W., Yoon, J. H., Lee, S. E., Cho, B. S., Eom, K. S., Kim, Y. J., Kim, H. J., Lee, S., Min, C. K., Cho, S. G., Kim, D. W., Min, W. S., & Lee, J. W. (2017). Beneficial Role of Low-Dose Antithymocyte Globulin in Unrelated Stem Cell Transplantation for Adult Patients with Acquired Severe Aplastic Anemia: Reduction of Graft-versus-Host Disease and Improvement of Graft-versus-Host Disease-Free, Failure-Free Survival Rate. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 23(9), 1498-1508. https://doi.org/10.1016/j.bbmt.2017.05.026
Park SS, et al. Beneficial Role of Low-Dose Antithymocyte Globulin in Unrelated Stem Cell Transplantation for Adult Patients With Acquired Severe Aplastic Anemia: Reduction of Graft-versus-Host Disease and Improvement of Graft-versus-Host Disease-Free, Failure-Free Survival Rate. Biol Blood Marrow Transplant. 2017;23(9):1498-1508. PubMed PMID: 28554856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Beneficial Role of Low-Dose Antithymocyte Globulin in Unrelated Stem Cell Transplantation for Adult Patients with Acquired Severe Aplastic Anemia: Reduction of Graft-versus-Host Disease and Improvement of Graft-versus-Host Disease-Free, Failure-Free Survival Rate. AU - Park,Sung-Soo, AU - Kwak,Dae Hun, AU - Jeon,Young-Woo, AU - Yoon,Jae-Ho, AU - Lee,Sung-Eun, AU - Cho,Byung-Sik, AU - Eom,Ki-Seong, AU - Kim,Yoo-Jin, AU - Kim,Hee-Je, AU - Lee,Seok, AU - Min,Chang-Ki, AU - Cho,Seok-Goo, AU - Kim,Dong-Wook, AU - Min,Woo-Sung, AU - Lee,Jong Wook, Y1 - 2017/05/26/ PY - 2017/02/16/received PY - 2017/05/22/accepted PY - 2017/5/31/pubmed PY - 2018/4/26/medline PY - 2017/5/31/entrez KW - Antithymocyte globulin KW - Aplastic anemia KW - Chronic graft-versus-host disease KW - Failure-free survival KW - Graft-versus-host disease free KW - Unrelated stem cell transplantation SP - 1498 EP - 1508 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 23 IS - 9 N2 - Stem cell transplantation (SCT) from an unrelated donor (URD) is often considered in patients with severe aplastic anemia (SAA) whom immunosuppressive therapy failed and matched sibling donor is not available. To reduce the incidence of graft-versus-host disease (GVHD) in URD SCT, introducting antithymocyte globulin (ATG) into the conditioning regimen has been proposed. Although ATG was shown to play a role in reducing GVHD in a cohort with diverse hematologic diseases, its role in SAA remains uncertain. The aim of this study was to determine the efficacy and toxicity of ATG in URD SCT for adult patients with SAA. We investigated 83 adult patients with SAA who underwent URD SCT between 2003 and 2014. The transplantation strategy consisted of total body irradiation (total 800 cGy) and cyclophosphamide (total 100 mg/kg to 120 mg/kg), followed by tacrolimus and a short-term methotrexate. We divided patients into 2 groups: group 1 (n = 25), which received HLA-matched (8/8) bone marrow (BM) without ATG, and group 2 (n = 58), which received SCT from either an HLA-mismatched donor or peripheral blood (PB). Thereafter, group 2 was subdivided according to ATG use into group 2A (without ATG, n = 26), which served as a historical cohort, and group 2B (with ATG, n = 32). Rabbit ATG (Thymoglobulin; Genzyme-Sanofi, Lyon, France) was used in group 2B at a dose of 2.5 mg/kg. The median age of all patients was 30 years (range, 17 to 59 years). The incidence of GVHD was significantly lower in group 2B than group 2A, as demonstrated by the rate of grade II to IV acute GVHD at day 100 (31.2% versus 61.5%, P = .003) and the rate of chronic GVHD at 3 years (21.9% versus 65.4%, P = .002). The overall survival rates of the 3 groups were similar. However, GVHD-free, failure-free survival (GFFS) was significantly higher in group 2B than group 2A (P = .034). A multivariable model identified use of ATG as an independent factor affecting grades II to IV acute GVHD (hazard ratio [HR], 2.902; 95% confidence interval [CI], 1.417 to 5.942; P = .004), chronic GVHD (HR , 3.005; 95% CI, 1.279 to 7.059; P = .012), and GFFS (HR, 2.363; 95% CI, 1.162 to 4.805; P = .014). Toxicities, including infectious complications, were not different among the 3 groups. In conclusion, low-dose ATG (2.5 mg/kg) can reduce the incidence of acute and chronic GVHD and improve the quality of life in patients with SAA who receive stem cells from either an HLA-mismatched donor or PB; importantly, these benefits are achieved without increased toxicity. Furthermore, ATG can be considered in URD SCT from HLA-matched BM cells. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/28554856/Beneficial_Role_of_Low_Dose_Antithymocyte_Globulin_in_Unrelated_Stem_Cell_Transplantation_for_Adult_Patients_with_Acquired_Severe_Aplastic_Anemia:_Reduction_of_Graft_versus_Host_Disease_and_Improvement_of_Graft_versus_Host_Disease_Free_Failure_Free_Survival_Rate_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(17)30492-5 DB - PRIME DP - Unbound Medicine ER -