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International Journal of Hematology

, Volume 105, Issue 1, pp 59–69 | Cite as

Clinical features and outcomes of patients with primary myelofibrosis in Japan: report of a 17-year nationwide survey by the Idiopathic Disorders of Hematopoietic Organs Research Committee of Japan

  • Katsuto Takenaka
  • Kazuya Shimoda
  • Naoyuki Uchida
  • Taizo Shimomura
  • Koji Nagafuji
  • Tadakazu Kondo
  • Hirohiko Shibayama
  • Takehiko Mori
  • Kensuke Usuki
  • Taichi Azuma
  • Yutaka Tsutsumi
  • Junji Tanaka
  • Hitomi Dairaku
  • Keitaro Matsuo
  • Keiya Ozawa
  • Mineo Kurokawa
  • Shunya Arai
  • Koichi Akashi
Original Article

Abstract

We conducted a 17-year nationwide survey (1999–2015) to elucidate the clinical outcomes of patients with primary myelofibrosis (PMF) in Japan. Questionnaires were sent annually to approximately 500 hematology departments. Newly diagnosed patients with PMF were enrolled in this study, and were followed up annually to collect prognostic information. Approximately 50 patients were enrolled per year, yielding a total of 780 patients with PMF included in this study. The median age at diagnosis was 66 years. At the time of analysis, the median survival duration was 47 months, and the 3-year overall survival rate was 59 %. Infection and disease transformation into acute leukemia were the most frequent causes of death. Of the proposed prognostic models for predicting the outcomes of PMF patients in Japan, the Dynamic International Prognostic Scoring System of PMF plus model was the most feasible. Forty-three patients received allogeneic hematopoietic stem cell transplantation (alloSCT) at a median of 343 days after diagnosis. This treatment significantly prolonged the survival of PMF patients, and the 3-year overall survival rate after first alloSCT was 84 %. A long-term registration study is required for further evaluation of prognosis and the impact of treatments on survival.

Keywords

Myelofibrosis Nationwide survey Long-term outcome 

Notes

Acknowledgments

This study was supported by a research grant from the Idiopathic Disorders of Hematopoietic Organs Research Committee of the Ministry of Health, Labor and Welfare of Japan (H23-Nanchi-Ippan-001, H26-Nanchi-Ippan-062, H27-Nanchi-Ippan-017, a Grant-in-Aid for Scientific Research (C) (to K.T., No. 26461424), and a Grant-in-Aid for Scientific Research (S) (to K.A., No. 16H06391). The authors are grateful to their collaborators for their valuable contributions and acknowledge all the institutions that participated in this study and are listed in the supplementary document.

Compliance with ethical standards

Conflict of interest

The authors declare that no conflicts of interest exist.

Supplementary material

12185_2016_2102_MOESM1_ESM.docx (17 kb)
Figure S1. Number of years of rainfall series for each station (DOCX 17 kb)

References

  1. 1.
    Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–51 Epub 2009/04/10.CrossRefPubMedGoogle Scholar
  2. 2.
    Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for myelofibrosis research and treatment. Blood. 2009;113(13):2895–901 Epub 2008/11/08.CrossRefPubMedGoogle Scholar
  3. 3.
    Cervantes F, Passamonti F, Barosi G. Life expectancy and prognostic factors in the classic BCR/ABL-negative myeloproliferative disorders. Leukemia. 2008;22(5):905–14 Epub 2008/04/04.CrossRefPubMedGoogle Scholar
  4. 4.
    Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124(16):2507–13 (quiz 615. Epub 2014/07/20).CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Dupriez B, Morel P, Demory JL, Lai JL, Simon M, Plantier I, et al. Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. Blood. 1996;88(3):1013–8.PubMedGoogle Scholar
  6. 6.
    Cervantes F, Pereira A, Esteve J, Rafel M, Cobo F, Rozman C, et al. Identification of ‘short-lived’ and ‘long-lived’ patients at presentation of idiopathic myelofibrosis. Br J Haematol. 1997;97(3):635–40 Epub 1997/06/01.CrossRefPubMedGoogle Scholar
  7. 7.
    Cervantes F, Dupriez B, Passamonti F, Vannucchi AM, Morra E, Reilly JT, et al. Improving survival trends in primary myelofibrosis: an international study. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(24):2981–7 (Epub 2012/07/25).CrossRefGoogle Scholar
  8. 8.
    Hultcrantz M, Kristinsson SY, Andersson TM, Landgren O, Eloranta S, Derolf AR, et al. Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30(24):2995–3001 (Epub 2012/07/18).CrossRefGoogle Scholar
  9. 9.
    Tefferi A. Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014;89(9):915–25 (Epub 2014/08/16).CrossRefPubMedGoogle Scholar
  10. 10.
    Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115(9):1703–8 (Epub 2009/12/17).CrossRefPubMedGoogle Scholar
  11. 11.
    Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(4):392–7 (Epub 2010/12/15).CrossRefGoogle Scholar
  12. 12.
    Geyer HL, Mesa RA. Therapy for myeloproliferative neoplasms: when, which agent, and how? Blood. 2014;124(24):3529–37 (Epub 2014/12/05).CrossRefPubMedGoogle Scholar
  13. 13.
    Cervantes F. How i treat myelofibrosis. Blood. 2014;124(17):2635–42 (Epub 2014/09/19).CrossRefPubMedGoogle Scholar
  14. 14.
    Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054–61.CrossRefPubMedGoogle Scholar
  15. 15.
    James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779–90.CrossRefPubMedGoogle Scholar
  17. 17.
    Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387–97.CrossRefPubMedGoogle Scholar
  18. 18.
    Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):e270.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006;108(10):3472–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90 (Epub 2013/12/12).CrossRefPubMedGoogle Scholar
  21. 21.
    Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405 (Epub 2013/12/12).CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2015;100(4):479–88 (Epub 2015/01/27).CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Tam CS, Kantarjian H, Cortes J, Lynn A, Pierce S, Zhou L, et al. Dynamic model for predicting death within 12 months in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(33):5587–93 (Epub 2009/09/30).CrossRefGoogle Scholar
  24. 24.
    Tefferi A, Jimma T, Gangat N, Vaidya R, Begna KH, Hanson CA, et al. Predictors of greater than 80% 2-year mortality in primary myelofibrosis: a Mayo Clinic study of 884 karyotypically annotated patients. Blood. 2011;118(17):4595–8 (Epub 2011/09/02).CrossRefPubMedGoogle Scholar
  25. 25.
    Laszlo J. Myeloproliferative disorders (MPD): myelofibrosis, myelosclerosis, extramedullary hematopoiesis, undifferentiated MPD, and hemorrhagic thrombocythemia. Semin Hematol. 1975;12(4):409–32 (Epub 1975/10/01).PubMedGoogle Scholar
  26. 26.
    Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100(7):2292–302 (Epub 2002/09/20).CrossRefPubMedGoogle Scholar
  27. 27.
    Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8 (Epub 2012/12/05).CrossRefPubMedGoogle Scholar
  28. 28.
    Demirtas H, Hedeker D. An imputation strategy for incomplete longitudinal ordinal data. Stat Med. 2008;27(20):4086–93 (Epub 2008/03/14).CrossRefPubMedGoogle Scholar
  29. 29.
    Deadmond MA, Smith-Gagen JA. Changing incidence of myeloproliferative neoplasms: trends and subgroup risk profiles in the USA, 1973-2011. J Cancer Res Clin Oncol. 2015;141(12):2131–8 Epub 2015/05/15.CrossRefPubMedGoogle Scholar
  30. 30.
    Nangalia J, Green TR. The evolving genomic landscape of myeloproliferative neoplasms. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2014;2014(1):287–96 (Epub 2015/02/20).Google Scholar
  31. 31.
    Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, Milosevic JD, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014;123(10):1544–51 (Epub 2013/12/25).CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Hidaka T, Shide K, Shimoda H, Kameda T, Toyama K, Katayose K, et al. The impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis: a prospective survey of 202 cases in Japan. Eur J Haematol. 2009;83(4):328–33.CrossRefPubMedGoogle Scholar
  33. 33.
    Murata M, Nishida T, Taniguchi S, Ohashi K, Ogawa H, Fukuda T, et al. Allogeneic transplantation for primary myelofibrosis with BM, peripheral blood or umbilical cord blood: an analysis of the JSHCT. Bone Marrow Transplant. 2014;49(3):355–60 (Epub 2013/11/26).CrossRefPubMedGoogle Scholar
  34. 34.
    Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA et al. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase 3 trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015;100(9):1139–45 (Epub 2015/06/13).Google Scholar

Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  • Katsuto Takenaka
    • 1
  • Kazuya Shimoda
    • 2
  • Naoyuki Uchida
    • 3
  • Taizo Shimomura
    • 4
  • Koji Nagafuji
    • 5
  • Tadakazu Kondo
    • 6
  • Hirohiko Shibayama
    • 7
  • Takehiko Mori
    • 8
  • Kensuke Usuki
    • 9
  • Taichi Azuma
    • 10
  • Yutaka Tsutsumi
    • 11
  • Junji Tanaka
    • 12
  • Hitomi Dairaku
    • 1
  • Keitaro Matsuo
    • 13
  • Keiya Ozawa
    • 14
  • Mineo Kurokawa
    • 15
  • Shunya Arai
    • 15
  • Koichi Akashi
    • 1
  1. 1.Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical SciencesFukuokaJapan
  2. 2.Department of Gastroenterology and Hematology, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
  3. 3.Department of HematologyToranomon HospitalTokyoJapan
  4. 4.Department of HematologyKumamoto Shinto General HospitalKumamotoJapan
  5. 5.Division of Hematology and Oncology, Department of MedicineKurume University School of MedicineKurumeJapan
  6. 6.Department of Hematology and Oncology, Graduate School of MedicineKyoto UniversityKyotoJapan
  7. 7.Department of Hematology and OncologyOsaka University Graduate School of MedicineOsakaJapan
  8. 8.Division of Hematology, Department of MedicineKeio UniversityTokyoJapan
  9. 9.Department of HematologyNTT Medical Center TokyoTokyoJapan
  10. 10.Department of Hematology, Clinical Immunology, and Infectious DiseasesEhime University Graduate School of MedicineEhimeJapan
  11. 11.Department of HematologyHakodate Municipal HospitalHokkaidoJapan
  12. 12.Department of HematologyTokyo Women’s Medical UniversityTokyoJapan
  13. 13.Division of Molecular MedicineAichi Cancer Center Research InstituteNagoyaJapan
  14. 14.The Institute of Medical ScienceThe University of TokyoTokyoJapan
  15. 15.Department of Hematology and Oncology, Graduate School of MedicineThe University of TokyoTokyoJapan

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