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Autotaxin is a potential predictive marker for the development of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation

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Abstract

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT), and stratification of the high-risk group before transplantation is significant. Serum autotaxin (ATX) levels have been reported to increase in patients with liver fibrosis caused by metabolic inhibition from liver sinusoidal endothelial cells. Considering that the pathophysiology of VOD/SOS begins with liver sinusoidal endothelial cell injury, an increase in serum ATX levels may precede the onset of VOD/SOS. A retrospective study with 252 patients, including 12 patients with VOD/SOS, who had received allo-HCT was performed. The cumulative incidence of VOD/SOS was higher in the group with serum ATX levels before conditioning (baseline ATX) above the upper reference limit (high ATX group, p < 0.001), and 1-year cumulative incidences were 22.7% (95% confidence interval [95%CI], 3.1–42.4%) and 3.5% (95%CI, 1.1–5.8%), respectively. In the multivariate analysis, elevated baseline ATX was identified as an independent risk factor for VOD/SOS development and showed an additive effect on the predictive ability of known risk factors. Furthermore, the incidence of VOD/SOS-related mortality was greater in the high ATX group (16.7% vs. 1.3%; p = 0.005). Serum ATX is a potential predictive marker for the development of VOD/SOS.

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Data availability

The datasets supporting the conclusions of this article are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the staff of the Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, for the preparation of serum samples. This work was supported by research funding from Tosoh Corporation.

Funding

We received reagents to measure serum autotaxin and borrowed the AIA-2000 analyzer from Tosoh Corporation (Tokyo, Japan). This study was supported by research funding from Tosoh Corporation.

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Author notes

  1. Kazuya Takemura

    Present address: Department of Laboratory Medicine and Medical Informatics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka, 545-8585, Japan

Authors and Affiliations

  1. Department of Central Clinical Laboratory, Osaka Metropolitan University Hospital, Osaka, Japan

    Kazuya Takemura, Mika Nakamae, Kentaro Ido, Hiroshi Kubota, Masayuki Hino & Hirohisa Nakamae

  2. Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Mika Nakamae, Hiroshi Okamura, Kazuki Sakatoku, Kentaro Ido, Yosuke Makuuchi, Masatomo Kuno, Teruhito Takakuwa, Asao Hirose, Mitsutaka Nishimoto, Yasuhiro Nakashima, Hideo Koh, Masayuki Hino & Hirohisa Nakamae

  3. Department of Laboratory Medicine and Medical Informatics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka-shi, Osaka, 545-8585, Japan

    Mika Nakamae, Hiroshi Okamura, Kentaro Ido & Masayuki Hino

  4. Department of Preventive Medicine and Environmental Health, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan

    Hideo Koh

  5. Bioscience Division, Tosoh Corporation, Kanagawa, Japan

    Koji Igarashi

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Contributions

K.T., M.Nakamae, and H.O. conceptualized and designed the study. K.T. and M. Nakamae acquired and analyzed data. K.T., M.Nakamae, H.O., and H.N. interpreted the analysis results. K.T. wrote the original draft manuscript. M.Nakamae, H.O., K.S., K.Ido, Y.M., M.K., T.T., A.H., M.Nishimoto, Y.N., H.Koh, K.Igarashi, H.Kubota, M.H., and H.N. interpreted the results and reviewed critically and revised the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Mika Nakamae.

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Ethical approval

This study was approved by the Ethics Committee of Osaka City University (the predecessor of Osaka Metropolitan University) Graduate School of Medicine (Approval no. 2020 − 213). This study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Consent to participate

According to our ethical guidelines and our institutional ethical committee, consent was obtained using an opt-out approach, where we provided information about the research framework and allowed participants to decline participation, rather than obtaining informed consent.

Competing interests

All authors’ potential conflicts of interest in this research area are listed below. Except for Tosoh Corp., no direct funding was received for this research. No assistance with medical writing or data analysis work was received from the following companies. A patent application is pending for the results of this research from our university and Tosoh Cooperation.　KT, KS, K Ido, AH and H Kubota have no conflicts of interests in this research area; M Nakamae: research funding from Veritas Corp. and honoraria to spouse (Please refer to HN disclosure); HO: research funding from Takeda Pharmaceutical Co., Ltd., and honoraria from Nippon Shinyaku Co., Ltd. and Asahi Kasei Pharma Corp.; YM: honoraria from Asahi Kasei Pharma Corp.; TT: research funding from Pfizer Japan Inc., Janssen Pharmaceutical K.K., and honoraria from Kyowa Kirin Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K. and Janssen Pharmaceutical K.K.; YN: research funding from Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., and Novartis Pharma K.K., and honoraria from Novartis Pharma K.K., Janssen Pharmaceutical K.K., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., and Kyowa Kirin Co., Ltd.; H Koh: research funding from Takeda Pharmaceutical Co., Ltd., and honoraria from Asahi Kasei Pharma Corp. and Takeda Pharmaceutical Co., Ltd., Novartis Pharma K.K., Nippon Shinyaku Co., Ltd., and Sumitomo Pharma Co., Ltd.; M.Nishimoto: research funding from Pfizer Japan Inc., and honoraria from Asahi Kasei Pharma Corp., Otsuka Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., and Janssen Pharmaceutical K.K.; K Igarashi: Employees of Tosoh Corportion,; MH: research funding from Tosoh Corp., Pfizer Japan Inc., Nippon Shinyaku Co., Ltd., Sekisui Medical Co., Ltd., ARKRAY, Inc. and donation for research from JCR Pharmaceuticals Co., Ltd., Kyowa Kirin Co., Ltd., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Asahi Kasei Pharma Corp., Sumitomo Pharma Co., Ltd., and Sekisui Medical Co., Ltd., and honoraria from Asahi Kasei Pharma Corp., Astellas Pharma Inc., Otsuka Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Nippon Kayaku Co., Ltd., Novartis Pharma K.K., Janssen Pharmaceutical K.K., Daiichi Sankyo Co., Ltd., Sumitomo Pharma Co., Ltd.; HN: research funding Novartis Pharma K.K., and Takeda Pharmaceutical Co., Ltd., and honoraria from Astellas Pharma Inc, Chugai Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Sumitomo Pharma Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma, and Janssen Pharmaceutical K.K.

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Takemura, K., Nakamae, M., Okamura, H. et al. Autotaxin is a potential predictive marker for the development of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Ann Hematol 103, 1705–1715 (2024). https://doi.org/10.1007/s00277-024-05685-0

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