Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors

doi:10.1038/s41409-021-01314-w

. 2021 Sep;56(9):2231-2240.

doi: 10.1038/s41409-021-01314-w. Epub 2021 May 7.

Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors

Souichi Shiratori¹, Junichi Sugita¹, Shigeo Fuji², Jun Aoki³, Masashi Sawa⁴, Yukiyasu Ozawa⁵, Daigo Hashimoto^{1

6}, Ken-Ichi Matsuoka⁷, Kazunori Imada⁸, Noriko Doki⁹, Takashi Ashida¹⁰, Yasunori Ueda¹¹, Masatsugu Tanaka¹², Yasushi Sawayama¹³, Tatsuo Ichinohe¹⁴, Seitaro Terakura¹⁵, Satoko Morishima¹⁶, Yoshiko Atsuta¹⁷, Takahiro Fukuda³, Takanori Teshima^{18

19}

Affiliations

¹ Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
² Department of Hematology, Osaka International Cancer Institute, Osaka, Japan.
³ Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
⁴ Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
⁵ Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
⁶ Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan.
⁷ Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan.
⁸ Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
⁹ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
¹⁰ Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University Hospital, Osakasayama, Japan.
¹¹ Department of Hematology/Oncology and Transfusion and Hemapheresis Center, Kurashiki Central Hospital, Kurashiki, Japan.
¹² Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
¹³ Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan.
¹⁴ Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
¹⁵ Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁶ Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
¹⁷ Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.
¹⁸ Department of Hematology, Hokkaido University Hospital, Sapporo, Japan. teshima@med.hokudai.ac.jp.
¹⁹ Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan. teshima@med.hokudai.ac.jp.

PMID: 33963304
DOI: 10.1038/s41409-021-01314-w

Free article

Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors

Souichi Shiratori et al. Bone Marrow Transplant. 2021 Sep.

Free article

. 2021 Sep;56(9):2231-2240.

doi: 10.1038/s41409-021-01314-w. Epub 2021 May 7.

Authors

Affiliations

¹ Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.
² Department of Hematology, Osaka International Cancer Institute, Osaka, Japan.
³ Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
⁴ Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
⁵ Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
⁶ Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan.
⁷ Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan.
⁸ Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
⁹ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
¹⁰ Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University Hospital, Osakasayama, Japan.
¹¹ Department of Hematology/Oncology and Transfusion and Hemapheresis Center, Kurashiki Central Hospital, Kurashiki, Japan.
¹² Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan.
¹³ Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan.
¹⁴ Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
¹⁵ Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁶ Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
¹⁷ Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.
¹⁸ Department of Hematology, Hokkaido University Hospital, Sapporo, Japan. teshima@med.hokudai.ac.jp.
¹⁹ Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan. teshima@med.hokudai.ac.jp.

PMID: 33963304
DOI: 10.1038/s41409-021-01314-w

Abstract

Antithymocyte globulin (ATG) has been shown to reduce chronic graft-versus-host disease (GVHD) particularly in allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors; however, anti-GVHD effects of lower doses of ATG remains to be elucidated. We conducted a nationwide retrospective study to compare the outcomes of unrelated PBSCT with or without rabbit ATG (thymoglobulin) in 287 patients. A median ATG dose was 2.0 mg/kg. The primary endpoint, the cumulative incidence of moderate-severe chronic GVHD at 2 years was 22.1% in the ATG group, which was significantly less than that in the non-ATG group (36.3%, P = 0.025). The ATG group had a higher incidence of immunosuppressant discontinuation, GVHD-free, relapse-free survival, and moderate-severe chronic GVHD-free, relapse-free survival at 2 years compared to the non-ATG group. The incidences of grade III-IV aGVHD and moderate-severe chronic GVHD were significantly higher in patients with high absolute lymphocyte count (ALC) before the administration of ATG, whereas relapse rate was significantly higher in patients with low ALC before ATG. In conclusion, low-dose ATG effectively suppresses chronic GVHD in unrelated PBSCT, and ALC before ATG may be a potential predictor for GVHD and relapse.

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Wakamatsu M, Murata M, Kanda J, Fukushima K, Fukuda T, Najima Y, Katayama Y, Ozawa Y, Tanaka M, Kanda Y, Eto T, Takada S, Kako S, Uchida N, Kawakita T, Yoshiko H, Ichinohe T, Atsuta Y, Terakura S; GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation. Wakamatsu M, et al. Int J Hematol. 2023 Jun;117(6):889-899. doi: 10.1007/s12185-023-03563-5. Epub 2023 Feb 22. Int J Hematol. 2023. PMID: 36814041

References

1. Friedrichs B, Tichelli A, Bacigalupo A, Russell NH, Ruutu T, Shapira MY, et al. Long-term outcome and late effects in patients transplantedwith mobilised blood or bone marrow: a randomised trial. Lancet Oncol. 2010;11:331–8. - PubMed - DOI
1. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N. Engl J Med. 2012;367:1487–96. - PubMed - DOI
1. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8. - PubMed - PMC - DOI
1. Solh M, Zhang X, Connor K, Brown S, Solomon SR, Morris LE, et al. Factors predicting graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation: multivariable analysis from a single center. Biol Blood Marrow Transpl. 2016;22:1403–9. - DOI
1. Inamoto Y, Kimura F, Kanda J, Sugita J, Ikegame K, Nakasone H, et al. Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups. Haematologica. 2016;101:1592–602. - PubMed - PMC - DOI

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[1] Friedrichs B, Tichelli A, Bacigalupo A, Russell NH, Ruutu T, Shapira MY, et al. Long-term outcome and late effects in patients transplantedwith mobilised blood or bone marrow: a randomised trial. Lancet Oncol. 2010;11:331–8. - PubMed - DOI

[2] Friedrichs B, Tichelli A, Bacigalupo A, Russell NH, Ruutu T, Shapira MY, et al. Long-term outcome and late effects in patients transplantedwith mobilised blood or bone marrow: a randomised trial. Lancet Oncol. 2010;11:331–8. - PubMed - DOI

[3] Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N. Engl J Med. 2012;367:1487–96. - PubMed - DOI

[4] Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N. Engl J Med. 2012;367:1487–96. - PubMed - DOI

[5] Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8. - PubMed - PMC - DOI

[6] Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8. - PubMed - PMC - DOI

[7] Solh M, Zhang X, Connor K, Brown S, Solomon SR, Morris LE, et al. Factors predicting graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation: multivariable analysis from a single center. Biol Blood Marrow Transpl. 2016;22:1403–9. - DOI

[8] Solh M, Zhang X, Connor K, Brown S, Solomon SR, Morris LE, et al. Factors predicting graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation: multivariable analysis from a single center. Biol Blood Marrow Transpl. 2016;22:1403–9. - DOI

[9] Inamoto Y, Kimura F, Kanda J, Sugita J, Ikegame K, Nakasone H, et al. Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups. Haematologica. 2016;101:1592–602. - PubMed - PMC - DOI

[10] Inamoto Y, Kimura F, Kanda J, Sugita J, Ikegame K, Nakasone H, et al. Comparison of graft-versus-host disease-free, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups. Haematologica. 2016;101:1592–602. - PubMed - PMC - DOI

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Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors

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Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors

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