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Vitamin K2 therapy for myelodysplastic syndromes (MDS) and post-MDS acute myeloid leukemia: information through a questionnaire survey of multi-center pilot studies in Japan

Leukemia volume 14, pages 1156–1157 (2000)Cite this article

Myelodysplastic syndromes (MDS) comprise a group of clonal hematological disorders characterized by dysplastic features of bone marrow cells, ineffective hematopoiesis, and cytopenia. There is a more than 30% overall risk of progression to acute myeloid leukemia (post-MDS AML). Since the median age of patients is 60–70 years, allogenic bone marrow transplantation can be performed only in a small population of these patients.12 High-dose chemotherapy achieves an acceptable response rate, but the high incidence of treatment-related death and the short duration of complete remission mean that there is no survival benefit.34 The establishment of new therapeutic strategies for high risk MDS and post-MDS AML, especially for elderly patients, is therefore an important clinical issue.

We previously reported that vitamin K2 (VK2: menaquinone-4) but not vitamin K1 induces apoptosis of primary cultured leukemia cells and leukemia cell lines in vitro.5 Using bone marrow cells derived from patients with refractory anemia with excess of blast (RAEB) and RAEB in transformation (RAEB-T), we further demonstrated that this apoptosis-inducing effect of VK2 was rather specific toward blastic cells compared with non-blastic population in vitro as assessed by multi-color flow cytometry.6 In contrast, it has been reported by others that VK2 also has differentiation-inducing activity in myeloid leukemia cell lines such as HL-60 and U937.7 Several recent clinical case reports suggest the clinical benefit of using VK2 for treating patients with MDS.89 In a refractory anemia (RA) case, daily oral administration of 45 mg of VK2 resulted in dramatic improvement of cytopenia leading to complete independence from blood transfusions.8 We have reported reduction in numbers of peripheral blast cells and concomitant improvement of anemia and thrombocytopenia in a case of RAEB-T with myelofibrosis after treatment with 90 mg/day of VK2.9 Since VK2 has been used to treat patients with osteoporosis, its non-toxicity and safety for long-term daily administration have already been well established,10 which appears to be of clinical benefit in treating elderly patients with MDS. Under these circumstances, the time is ripe for a large-scale randomized trial for VK2 therapy in MDS. As the first step toward a prospective clinical study, we performed a questionnaire survey on the results of individual pilot studies of VK2 for MDS and post-MDS AML to collect information regarding efficiency, effective subgroup of MDS for VK2 therapy, optimal dose and administration route, and length of time until clinical response.

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Acknowledgements

This study was supported by Health Science Research Grants to Research Committee for Idiopathic Hemopoietic Disorders of the Ministry of Health and Welfare in Japan.

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Authors and Affiliations

  1. First Department of Internal Medicine, Tokyo Medical University, Japan

    K Miyazawa, J Nishimaki & K Ohyashiki

  2. Research Committee for Idiopathic Hemopoietic Disorders of the Ministry of Health and Welfare in Japan,

    K Ohyashiki, S Kuriya, T Hotta, M Teramura, H Mizoguchi, T Uchiyama & M Omine

  3. Third Department of Internal Medicine, Iwate University School of Medicine, Japan

    S Enomoto & S Kuriya

  4. Fourth Department of Internal Medicine, Toukai University School of Medicine, Japan

    R Fukuda & T Hotta

  5. Department of Hematology, Tokyo Women's Medical University, School of Medicine, Japan

    M Teramura & H Mizoguchi

  6. Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Japan

    T Uchiyama

  7. Division of Hematology, Internal Medicine, Showa University Fujigaoka Hospital, Japan

    M Omine

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Miyazawa, K., Nishimaki, J., Ohyashiki, K. et al. Vitamin K2 therapy for myelodysplastic syndromes (MDS) and post-MDS acute myeloid leukemia: information through a questionnaire survey of multi-center pilot studies in Japan. Leukemia 14, 1156–1157 (2000). https://doi.org/10.1038/sj.leu.2401790

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