Skip to main content
Top
Published in: International Journal of Hematology 6/2012

01-12-2012 | Original Article

Low incidences of acute and chronic graft-versus-host disease after unrelated bone marrow transplantation with low-dose anti-T lymphocyte globulin

Authors: Kazuo Hatanaka, Shigeo Fuji, Kazuhiro Ikegame, Ruri Kato, Atsushi Wake, Michihiro Hidaka, Toshiro Ito, Masami Inoue, Yoshihisa Nagatoshi, Akiyoshi Takami, Naokuni Uike, Hisashi Sakamaki, Hiromasa Yabe, Yasuo Morishima, Ritsuro Suzuki, Yoshiko Atsuta, Takahiro Fukuda

Published in: International Journal of Hematology | Issue 6/2012

Login to get access

Abstract

Anti-T lymphocyte globulin (ATG) is commonly used as prophylaxis for graft-versus-host disease (GVHD), especially in patients who are at high risk of GVHD. The appropriate dosage of ATG in Japan has not yet been assessed. We therefore conducted a nationwide survey of patients who received ATG-Fresenius as GVHD prophylaxis for unrelated bone marrow transplantation (uBMT). A total of 86 patients were identified (median age 31 years, range 1–68). The median total dose of ATG was 10 mg/kg. The cumulative incidence of neutrophil engraftment was 90 %. The probability of 2-year overall survival (OS) was 67 %. The cumulative incidence of 2-year non-relapse mortality was 25 %. The incidences of grade II–IV and grade III–IV acute GVHD were 20 and 8 %, respectively. The incidences of chronic and extensive chronic GVHD were 19 and 8 %, respectively. In adult patients, there was a reduction of acute GVHD with high-dose ATG (>10 mg/kg), which did not reach statistical significance. In conclusion, the addition of low-dose ATG to GVHD prophylaxis in Japanese patients who received uBMT resulted in decreased incidences of both acute and chronic GVHD without compromising OS. The effects of low-dose ATG should be assessed in a prospective clinical trial.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101.PubMedCrossRef Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101.PubMedCrossRef
2.
go back to reference Horan JT, Logan BR, Agovi-Johnson MA, Lazarus HM, Bacigalupo AA, Ballen KK, et al. Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made? J Clin Oncol. 2011;29:805–13.PubMedCrossRef Horan JT, Logan BR, Agovi-Johnson MA, Lazarus HM, Bacigalupo AA, Ballen KK, et al. Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made? J Clin Oncol. 2011;29:805–13.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference Socié 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.PubMedCrossRef Socié 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.PubMedCrossRef
5.
go back to reference Kumar A, Mhaskar AR, Reljic T, Mhaskar RS, Kharfan-Dabaja MA, Anasetti C, et al. Antithymocyte globulin for acute-graft-versus-host-disease prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation: a systematic review. Leukemia. 2012;26:582–8.PubMedCrossRef Kumar A, Mhaskar AR, Reljic T, Mhaskar RS, Kharfan-Dabaja MA, Anasetti C, et al. Antithymocyte globulin for acute-graft-versus-host-disease prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation: a systematic review. Leukemia. 2012;26:582–8.PubMedCrossRef
6.
go back to reference Oh H, Loberiza FR Jr, Zhang MJ, Ringdén O, Akiyama H, Asai T, et al. Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations. Blood. 2005;105:1408–16.PubMedCrossRef Oh H, Loberiza FR Jr, Zhang MJ, Ringdén O, Akiyama H, Asai T, et al. Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations. Blood. 2005;105:1408–16.PubMedCrossRef
7.
go back to reference Hahn T, McCarthy PL Jr, Zhang MJ, Wang D, Arora M, Frangoul H, et al. Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol. 2008;26:5728–34.PubMedCrossRef Hahn T, McCarthy PL Jr, Zhang MJ, Wang D, Arora M, Frangoul H, et al. Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol. 2008;26:5728–34.PubMedCrossRef
8.
go back to reference Kim HJ, Min WS, Cho BS, Eom KS, Kim YJ, Min CK, et al. Successful prevention of acute graft-versus-host disease using low-dose antithymocyte globulin after mismatched, unrelated, hematopoietic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant. 2009;15:704–17.PubMedCrossRef Kim HJ, Min WS, Cho BS, Eom KS, Kim YJ, Min CK, et al. Successful prevention of acute graft-versus-host disease using low-dose antithymocyte globulin after mismatched, unrelated, hematopoietic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant. 2009;15:704–17.PubMedCrossRef
9.
go back to reference Remberger M, Svahn BM, Mattsson J, Ringdén O. Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation. Transplantation. 2004;78:122–7.PubMed Remberger M, Svahn BM, Mattsson J, Ringdén O. Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation. Transplantation. 2004;78:122–7.PubMed
10.
go back to reference Mohty M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia. 2007;21:1387–94.PubMedCrossRef Mohty M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia. 2007;21:1387–94.PubMedCrossRef
11.
go back to reference Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol. 2007;86:269–74.PubMedCrossRef Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol. 2007;86:269–74.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference 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;15:825–8.PubMed 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;15:825–8.PubMed
15.
go back to reference Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.PubMedCrossRef Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.PubMedCrossRef
16.
go back to reference Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.PubMedCrossRef Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.PubMedCrossRef
17.
go back to reference Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K, et al. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood. 2002;99:4200–6.PubMedCrossRef Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K, et al. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood. 2002;99:4200–6.PubMedCrossRef
18.
go back to reference Ozawa S, Nakaseko C, Nishimura M, Maruta A, Cho R, Ohwada C, et al. Chronic graft-versus-host disease after allogeneic bone marrow transplantation from an unrelated donor: incidence, risk factors and association with relapse: a report from the Japan Marrow Donor Program. Br J Haematol. 2007;137:142–51.PubMedCrossRef Ozawa S, Nakaseko C, Nishimura M, Maruta A, Cho R, Ohwada C, et al. Chronic graft-versus-host disease after allogeneic bone marrow transplantation from an unrelated donor: incidence, risk factors and association with relapse: a report from the Japan Marrow Donor Program. Br J Haematol. 2007;137:142–51.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference Soiffer RJ, Lerademacher J, Ho V, Kan F, Artz A, Champlin RE, et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood. 2011;117:6963–70.PubMedCrossRef Soiffer RJ, Lerademacher J, Ho V, Kan F, Artz A, Champlin RE, et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood. 2011;117:6963–70.PubMedCrossRef
Metadata
Title
Low incidences of acute and chronic graft-versus-host disease after unrelated bone marrow transplantation with low-dose anti-T lymphocyte globulin
Authors
Kazuo Hatanaka
Shigeo Fuji
Kazuhiro Ikegame
Ruri Kato
Atsushi Wake
Michihiro Hidaka
Toshiro Ito
Masami Inoue
Yoshihisa Nagatoshi
Akiyoshi Takami
Naokuni Uike
Hisashi Sakamaki
Hiromasa Yabe
Yasuo Morishima
Ritsuro Suzuki
Yoshiko Atsuta
Takahiro Fukuda
Publication date
01-12-2012
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 6/2012
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-012-1209-4

Other articles of this Issue 6/2012

International Journal of Hematology 6/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine