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Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors

Manabu Wakamatsu, Seitaro Terakura, Kazuteru Ohashi, Takahiro Fukuda, Yukiyasu Ozawa, Heiwa Kanamori, Masashi Sawa, Naoyuki Uchida, Shuichi Ota, Akiko Matsushita, Yoshinobu Kanda, Hirohisa Nakamae, Tatsuo Ichinohe, Koji Kato, Makoto Murata, Yoshiko Atsuta and Takanori Teshima on behalf of the GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation

Key Points

  • ATG decreased OS and GRFS in CB, but improved OS and GRFS in 1-MMUD.

Abstract

Antithymocyte globulin (ATG) is widely used to reduce acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). To clarify the different impacts of ATG for conditioning across different donor types, we retrospectively analyzed patients with acute leukemia (n = 6617) who underwent hematopoietic stem cell transplantation between 2008 and 2015 with ATG (n = 279) or without ATG (n = 6338). Because thymoglobulin is the only ATG drug approved for GVHD prophylaxis in Japan since September 2008, we included thymoglobulin alone in the present analysis. The survivors’ median follow-up time was 1081 days. Patients were categorized into 5 groups: cord blood (CB; n = 1915), matched related donor (n = 1772), 1-antigen mismatched related donor (1-MMRD; n = 225), matched unrelated donor (MUD; n = 1742), and 1-allele mismatched unrelated donor (1-MMUD; n = 963). In multivariate analysis, ATG decreased overall survival (hazard ratio [HR], 1.403; P = .054) and GVHD-free/relapse-free survival (GRFS) (HR, 1.458; P = .053) in association with increased nonrelapse mortality (NRM) (HR, 1.608; P = .03) with CB, whereas it improved GRFS (HR, 0.515; P < .01) and decreased grades II to IV aGVHD (HR, 0.576; P < .01), extensive cGVHD (HR, 0.460; P = .02), and NRM (HR, 0.545; P = .03) with 1-MMUD. ATG did not impact survival with 1-MMRD and MUD. The use of ATG in conditioning is beneficial due to the reduction in acute/chronic GVHD without increasing NRM or disease relapse only in 1-MMUD transplantation. On the other hand, ATG is not recommended for CB transplantation.

  • Submitted September 4, 2018.
  • Accepted November 16, 2018.
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