Bortezomib Against Refractory Antibody-Mediated Rejection After ABO-Incompatible Living-Donor Liver Transplantation: Dramatic Effect in Acute-Phase?

Tetsuya Tajima, MD; Koichiro Hata, MD, PhD; Hideaki Okajima, MD, PhD; Momoko Nishikori, MD, PhD; Kentaro Yasuchika, MD, PhD; Jiro Kusakabe, MD; Atsushi Yoshizawa, MD, PhD; Ken Fukumitsu, MD, PhD; Takayuki Anazawa, MD, PhD; Hirokazu Tanaka, MD; Seidai Wada, MD, PhD; Junshi Doi, MD; Akifumi Takaori-Kondo, MD, PhD; Shinji Uemoto, MD, PhD

doi:10.1097/TXD.0000000000000932

Transplantation Direct (Oct 2019)

Bortezomib Against Refractory Antibody-Mediated Rejection After ABO-Incompatible Living-Donor Liver Transplantation: Dramatic Effect in Acute-Phase?

Tetsuya Tajima, MD,
Koichiro Hata, MD, PhD,
Hideaki Okajima, MD, PhD,
Momoko Nishikori, MD, PhD,
Kentaro Yasuchika, MD, PhD,
Jiro Kusakabe, MD,
Atsushi Yoshizawa, MD, PhD,
Ken Fukumitsu, MD, PhD,
Takayuki Anazawa, MD, PhD,
Hirokazu Tanaka, MD,
Seidai Wada, MD, PhD,
Junshi Doi, MD,
Akifumi Takaori-Kondo, MD, PhD,
Shinji Uemoto, MD, PhD

Affiliations

Tetsuya Tajima, MD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Koichiro Hata, MD, PhD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hideaki Okajima, MD, PhD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Momoko Nishikori, MD, PhD: 2 Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Kentaro Yasuchika, MD, PhD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Jiro Kusakabe, MD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Atsushi Yoshizawa, MD, PhD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Ken Fukumitsu, MD, PhD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Takayuki Anazawa, MD, PhD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Hirokazu Tanaka, MD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Seidai Wada, MD, PhD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Junshi Doi, MD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Akifumi Takaori-Kondo, MD, PhD: 2 Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Shinji Uemoto, MD, PhD: 1 Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.

DOI: https://doi.org/10.1097/TXD.0000000000000932
Journal volume & issue: Vol. 5, no. 10
p. e491

Abstract

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Antibody-mediated rejection (AMR) is a refractory rejection after donor-specific antibody-positive or ABO blood-type incompatible (ABOi) organ transplantation. Rituximab dramatically improved the outcome of ABOi living-donor liver transplantation (LDLT); however, an effective treatment for posttransplant AMR, once occurred, is yet to be established. A 44-year-old woman with biliary cirrhosis underwent ABOi-LDLT from her sister (AB-to-A). Pretransplant rituximab diminished CD19/20-positive B lymphocytes to 0.6%/0.0%; however, AMR occurred on posttransplant day-6 with marked increase in both CD19/20 cells (17.1%/5.8%) and anti-B IgM/G-titers (1024/512). Despite rituximab readministration, steroid-pulse, intravenous immunoglobulin, and plasmapheresis, AMR was uncontrollable, with further increasing CD19/20 cells (23.0%/0.0%) and antibody-titers (2048/512). Bortezomib (1.0 mg/m2) was thus administered on posttransplant day-9, immediately ameliorating CD19/20 cells (1.3%/0.0%) and antibody-titers (<256/128). Complete remission of refractory AMR was obtained by just 2 doses of bortezomib. Her liver function has been stable thereafter for over 3 years. This case highlighted the efficacy of bortezomib against refractory AMR after ABOi-LDLT. Unlike previous reports, the efficacy was very dramatic, presumably due to the administration timing near the peak of acute-phase AMR.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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