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Serum ferritin levels at diagnosis predict prognosis in patients with low blast count myelodysplastic syndromes

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Abstract

Serum ferritin, a marker of systemic iron status, is considered a prognostic factor for patients with myelodysplastic syndromes (MDS), despite the lack of supporting evidence. We investigated the association between serum ferritin levels at diagnosis and the prognoses of Japanese MDS patients with bone marrow blasts < 5% and peripheral blood blasts < 2%. Three hundred and ninety patients with cytopenia were registered prospectively in the multicenter database, among whom 107 patients with MDS (72 males and 35 females, with a median age of 70 years) met the eligibility criteria. The median serum ferritin level at diagnosis was 204 ng/mL; we divided the cohort into low (n = 56) and high (n = 51) ferritin groups using a cutoff of 210 ng/mL. Kaplan–Meier analyses revealed that the 3-year overall survival (OS) of the high ferritin group was significantly shorter than that of the low ferritin group (66% and 79%, respectively). The cumulative incidences of leukemic progression were similar between the groups. On multivariate analysis, age, blast percentage, cytogenetic abnormalities, and serum ferritin levels at diagnosis were independently associated with OS in our patients. Thus, modest elevations of ferritin levels at diagnosis may influence the prognoses of patients with MDS who have low blast counts.

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Acknowledgements

The authors thank the patients, their families, all the investigators including Drs. Yukiharu Nakabo (The Center for Hematological Diseases, Takeda General Hospital), Takahiko Utsumi (Department of Hematology and Oncology, Shiga General Hospital), Tatsuo Ichinohe (Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University), Hirohiko Shibayama (Department of Hematology and Oncology, Osaka University Graduate School of Medicine), Yasuyoshi Morita (Division of Hematology and Rheumatology, Department of Internal Medicine, Kindai University Faculty of Medicine), Masayuki Shiseki (Department of Hematology, Tokyo Women’s Medical University), Masayoshi Kobune (Department of Hematology, Sapporo Medical University School of Medicine), Naoshi Obara (Department of Hematology, Graduate School of Comprehensive Human Sciences, Tsukuba University), Wataru Takahashi (Department of Hematology and Oncology, Dokkyo Medical University Hospital), and nurses in the participating institutions of this study. The authors also thank Dr. Keiya Ozawa (Institute of Medical Science, the University of Tokyo) for his mentorship; and Drs. Mizuki Watanabe, Kazue Miyamoto-Arimoto, and Tasuki Uchiyama, and Ms. Tomoko Okuda and Yukiko Takada (Department of Hematology and Oncology, Kyoto University) for their technical assistance with the construction of the database.

Funding

This work was partially supported by the Research Program of Intractable Disease provided by the Ministry of Health, Labor, and Welfare (MHLW) of Japan (H20-Nanchi-Ippan-001, H23-Nanchi-Ippan-001, H26-Nanchi-Ippan-062, H27-Nanchi-Ippan-016, H29-Nanchi-Ippan-026).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Hiroshi Kawabata, Maki Shindo-Ueda, Junya Kanda & Akifumi Takaori-Kondo

  2. Department of Hematology and Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa-ken, 920-0293, Japan

    Hiroshi Kawabata

  3. Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan

    Kensuke Usuki

  4. Department of Laboratory Medicine, Kawasaki Medical School, Okayama, Japan

    Kaoru Tohyama

  5. Department of Hemato-Oncology, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan

    Akira Matsuda

  6. Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Saitama Medical University, Moroyama, Saitama, Japan

    Kayano Araseki

  7. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan

    Tomoko Hata & Yasushi Miyazaki

  8. Department of Hematology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan

    Takahiro Suzuki

  9. School of Medical Technology, Faculty of Health and Medical Care, Saitama Medical University, Hidaka, Saitama, Japan

    Hidekazu Kayano

  10. Clinical Laboratory Center, Dokkyo Medical University Hospital, Mibu, Tochigi, Japan

    Kei Shimbo

  11. Department of Hematology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan

    Shigeru Chiba

  12. Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan

    Takayuki Ishikawa

  13. Department of Hematology, Medical Research Institute Kitano Hospital, Osaka, Japan

    Nobuyoshi Arima

  14. Department of Hematology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan

    Masaharu Nohgawa

  15. Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Mineo Kurokawa

  16. Department of Hematology, Tokyo Metropolitan Police Hospital, Tokyo, Japan

    Shunya Arai

  17. Department of Hematology and Oncology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan

    Kinuko Mitani

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  1. Hiroshi Kawabata
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  2. Kensuke Usuki
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  20. Akifumi Takaori-Kondo
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Dr. Kawabata reports personal fees from Nippon Shinyaku Co., Ltd. outside the submitted work. Dr. Tohyama reports personal fees from Celgene Corporation and SymBio Pharmaceuticals Ltd. outside the submitted work. Dr. Matsuda reports personal fees from Kyowa Hakko Kirin Co., Ltd., Nippon Shinyaku Co., Ltd., GlaxoSmithKline K. K., Celgene Corporation, Alexion Pharmaceuticals, Inc., Sanofi K. K., Beckman Coulter K. K., and Shire Japan K.K.; grants and personal fees from Sumitomo Dainippon Pharma Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Novartis Pharma K. K.; and grants from Astellas Pharm Inc., Asahi Kasei Pharma Co., Ltd., Eisai Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan Inc., MSD K. K., Daiichi Sankyo Co., Ltd., Abbvie GK, and HUYA Bioscience International outside the submitted work. Dr. Suzuki reports personal fees from Novartis Pharma K.K., Nippon Shinyaku Co., Ltd., Celgene Corporation, and Kyowa Hakko Kirin Co., Ltd.; grants from Astellas Pharma Inc. outside the submitted work. Mr. Shimbo reports personal fees from Celgene Corporation, and Bristol-Myers Squibb outside the submitted work. Dr. Chiba reports grants from Kyowa Hakko Kirin Co., Ltd., Bristol-Myers Squibb, and Astellas Pharma Inc. outside the submitted work. Dr. Miyazaki reports personal fees from Novartis Pharma K.K., Dainippon Sumitomo Pharma Co., Ltd., Celgene Corporation, and SymBio Pharmaceuticals Ltd.; personal fees and grants from Kyowa Hakko Kirin Co., Ltd.; grants from Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Pfizer Seiyaku K.K. outside the submitted work. Dr. Mitani reports grants and personal fees from Kyowa-Hakko Kirin Co., Ltd.; and grants from Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., Teijin Pharma Ltd., Japan Blood Products Organization, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Toyama Chemical Co., Ltd. outside the submitted work. Dr. Kurokawa reports personal fees from Shionogi & Co., Ltd. and Celgene Corporation; grants from Kyowa Hakko Kirin Co., Ltd., Nippon Shinyaku Co., Ltd., Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Novartis Pharma K.K., Bristol-Myers Squibb, and Pfizer Seiyaku K.K. outside the submitted work. Dr. Takaori-Kondo reports personal fees from Yanssen Pharmaceutical K.K., Novartis Pharma K.K., and Bristol-Myers Squibb; personal fees and grants from Pfizer Seiyaku K.K. and Celgene Corporation; and grants from Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Astellas Pharma Inc., Japan Blood Products Organization, Eisai Co., Ltd., Shionogi & Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Otsuka Pharmaceutical Co., Ltd. outside the submitted work.

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Kawabata, H., Usuki, K., Shindo-Ueda, M. et al. Serum ferritin levels at diagnosis predict prognosis in patients with low blast count myelodysplastic syndromes. Int J Hematol 110, 533–542 (2019). https://doi.org/10.1007/s12185-019-02710-1

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