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Risk factors for early in-hospital death in patients who developed coagulopathy during induction therapy for acute promyelocytic leukemia: a nationwide analysis in Japan

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Abstract

To prevent early death, management of coagulopathy is important in patients with untreated acute promyelocytic leukemia (APL). This study aimed to clarify factors associated with in-hospital death in patients with coagulopathy during induction therapy for APL. We retrospectively identified patients with newly diagnosed APL who received induction therapy including all-trans retinoic acid (ATRA) and developed coagulopathy, using a nationwide inpatient database in Japan. Of 1115 eligible patients, 175 (15%) died at a median of 13 days (interquartile range, 7–30) after admission. In the multivariable analysis, compared with younger patients (aged < 40 years), the occurrence of in-hospital death was significantly more common among older patients (aged ≥ 40 and < 60 years: odds ratio = 2.58 [95% confidence interval: 1.29–5.19]; aged ≥ 60 and < 80 years: 7.66 [3.89–15.10]; aged ≥ 80 years: 16.83 [7.41–38.21]). Delayed initiation of ATRA and no conventional chemotherapy were significantly associated with in-hospital death (1.79 [1.16–2.76] and 2.40 [1.47–3.92], respectively). A total of 699 patients (63%) received anticoagulant therapies, but none of these was significantly associated with lower mortality. Although the present study was constrained by a lack of laboratory findings because of database limitations, the results showed that untreated patients with APL, especially the elderly, had a poor prognosis. Immediate administration of ATRA may reduce in-hospital mortality.

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Funding

This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (19AA2007 and H30-Policy-Designated-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (17H04141). These funding bodies had no role in the design of the study; collection, analysis, or interpretation of the data; or writing of the manuscript.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Kensuke Matsuda, Kazuhiro Toyama, Kumi Nakazaki & Mineo Kurokawa

  2. Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Taisuke Jo

  3. Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Hiroki Matsui & Hideo Yasunaga

  4. Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Kiyohide Fushimi

  5. Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Mineo Kurokawa

Authors
  1. Kensuke Matsuda
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  2. Taisuke Jo
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  3. Kazuhiro Toyama
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  4. Kumi Nakazaki
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  5. Hiroki Matsui
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  7. Hideo Yasunaga
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  8. Mineo Kurokawa
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Contributions

K.M. and T.J. designed the research. K.T. and K.N. advised on the research design and analyses. H.Y., H.M., and K.F. collected the patient data. K.M. and T.J. analyzed the data. K.M. wrote the manuscript. All the authors revised the manuscript and approved the final manuscript.

Corresponding author

Correspondence to Kensuke Matsuda.

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Conflict of interest

K.M. received a lecture fee from Kyowa Kirin. T.J. received consigned research funding from Tsumura and works in the laboratory of a joint program with Tsumura. K.T. received lecture fees from Kyowa Kirin, Eisai, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Nippon Shinyaku, Chugai Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, and Takeda Pharmaceutical. K.F. received a scholarship donation from Chugai Pharmaceutical. M.K. received research funding from Pfizer, Otsuka Pharmaceutical, Chugai Pharmaceutical, Astellas, Kyowa Kirin, Takeda Pharmaceutical, MSD, Teijin, Eisai, Sumitomo Dainippon Pharma, Ono Pharmaceutical, and Nippon Shinyaku. M.K. received advisory fees from Daiichi Sankyo, Kyowa Kirin, Celgene, and Bioverativ Japan. M.K. received lecture fees from MSD, Astellas, Eisai, Otsuka Pharmaceutical, Ono Pharmaceutical, Shire Plc, Celgene, Daiichi Sankyo, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, Bristol-Myers Squibb, Jansen Pharmaceutical, Nippon Shinyaku. and Kyowa Kirin.

None of this funding was related to the current study.

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Matsuda, K., Jo, T., Toyama, K. et al. Risk factors for early in-hospital death in patients who developed coagulopathy during induction therapy for acute promyelocytic leukemia: a nationwide analysis in Japan. Ann Hematol 100, 2613–2619 (2021). https://doi.org/10.1007/s00277-021-04620-x

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  • DOI: https://doi.org/10.1007/s00277-021-04620-x

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