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Antithymocyte Globulin Potentially Could Overcome an Adverse Effect of Acute Graft-versus-Host Disease in Matched-Related Peripheral Blood Stem Cell Transplantation.

Abstract
Previous Japanese studies have shown that bone marrow transplantation (BMT) is associated with better survival compared with peripheral blood stem cell transplantation (PBSCT) from a matched related donor (MRD). PBSCT recipients have shown higher incidences of severe graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) compared with BMT recipients. In recent years, the efficacy and safety of antithymocyte globulin (ATG) for PBSCT recipients has been evaluated worldwide. In the present study, we aimed to compare BMT and PBSCT recipients to identify current improvements and unmet needs among MRD PBSCT recipients. In addition, we evaluated the impact of ATG administration on the outcomes of PBSCT recipients. We retrospectively analyzed patients age ≥16 years with acute leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia who underwent their first BMT or PBSCT from an MRD between 2009 and 2018 in Japan. A total of 3599 transplantations were performed (BMT, n = 1218; PBSCT without ATG [PBSCT-ATG(-)], n = 2288; PBSCT with ATG [PBSCT-ATG(+)], n = 93). The PBSCT-ATG(-) group had a higher NRM (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.08 to 1.57; P = .005) and lower overall survival (OS) (HR, 1.16; 95% CI, 1.04 to 1.30; P = .011) compared with the BMT group. Furthermore, the PBSCT-ATG(-) group had higher incidences of grade III-IV, stage 2-4 gut, high-risk, and steroid-refractory acute GVHD compared with the BMT group. Acute GVHD had a negative impact on NRM and OS. The PBSCT-ATG(-) group also was associated with an elevated risk of chronic GVHD (HR, 1.89; 95% CI, 1.24 to 2.57; P < .001) and extensive chronic GVHD (HR, 1.44; 95% CI, 1.23 to 1.68; P < .001). The incidences of acute GVHD, chronic GVHD, and NRM and chronic GVHD-free relapse-free survival rates were comparable between the PBSCT-ATG(+) and BMT groups. The OS of patients with acute GVHD was similar in the 3 donor groups. Patients treated with reduced-intensity conditioning in the PBSCT-ATG(+) group had a higher relapse rate and lower OS rate compared with those in the BMT group. In this Japanese cohort, standard calcineurin inhibitor-based GVHD prophylaxis was not sufficient for recipients of MRD PBSCT because of the high incidence of severe acute GVHD. Prophylactic ATG was found to be a promising strategy against GVHD.
AuthorsKotaro Miyao, Yachiyo Kuwatsuka, Makoto Murata, Koji Nagafuji, Takanori Teshima, Yuki Takeuchi, Souichi Shiratori, Yuho Najima, Naoyuki Uchida, Masatsugu Tanaka, Masashi Sawa, Shuichi Ota, Takahiro Fukuda, Yukiyasu Ozawa, Shinichi Kako, Toshiro Kawakita, Takahide Ara, Junji Tanaka, Yoshinobu Kanda, Yoshiko Atsuta, Junya Kanda, Seitaro Terakura, GVHD Working Group and Donor/Source Working Group of the Japanese Society for Transplantation and Cellular Therapy
JournalTransplantation and cellular therapy (Transplant Cell Ther) Vol. 28 Issue 3 Pg. 153.e1-153.e11 (03 2022) ISSN: 2666-6367 [Electronic] United States
PMID34954151 (Publication Type: Journal Article)
CopyrightCopyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Antilymphocyte Serum
Topics
  • Adolescent
  • Antilymphocyte Serum (therapeutic use)
  • Graft vs Host Disease (etiology)
  • Humans
  • Leukemia, Myeloid, Acute (therapy)
  • Peripheral Blood Stem Cell Transplantation (adverse effects)
  • Recurrence
  • Retrospective Studies

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