International Journal of Hematology

, Volume 103, Issue 4, pp 423–428 | Cite as

Splenic irradiation provides transient palliation for symptomatic splenomegaly associated with primary myelofibrosis: a report on 14 patients

  • Akira Kitanaka
  • Katsuto Takenaka
  • Kotaro Shide
  • Toshihiro Miyamoto
  • Tadakazu Kondo
  • Keiya Ozawa
  • Mineo Kurokawa
  • Koichi Akashi
  • Kazuya ShimodaEmail author
Original Article


We retrospectively analyzed the outcomes of 14 patients with primary myelofibrosis who were treated with splenic irradiation (SI) for symptomatic splenomegaly between January 2000 and December 2012 at 12 hospitals. Median age at the time of SI was 67 years (range 47–76). The median dose of radiation per course was 5 Gy, administered in a median of eight fractions. Spleen size was reduced in 93 % of patients, and persisted for a median of 2.2 months (range 0.1–13.8). Symptom relief occurred in 86 % of patients, and lasted for a median of 2.5 months (range 0.1–16.5). Although SI provided a high rate of palliation for patients with symptomatic splenomegaly, the responses were transient. Significant thrombopenia (<25 × 109/L) occurred in eight patients (57 %), and neutropenia (<0.5 × 109/L) was observed in seven (50 %). Nine patients (64 %) required an increased number of red blood cell transfusions after SI. Five patients (36 %) developed serious infections, with two deaths (14 %), as a result of SI-induced cytopenia. The median survival for all patients after SI was 18.5 months (range 0.1–71.9). The Dynamic International Prognostic Scoring System model effectively distinguished the prognosis after SI between patients in the intermediate-2 and high-risk groups.


Myelofibrosis Splenomegaly Splenic irradiation Palliation 



This study was supported by the National Research Group on Idiopathic Bone Marrow Failure Syndromes. The authors would like to express their gratitude to Dr. Keichiro Mihara (Hiroshima University Hospital), Dr. Hideo Tanaka (Hiroshima City Asa Citizens Hospital), Dr. Hironori Take (Toyonaka Municipal Hospital), Dr. Toshie Ogasawara (Tokyo Women’s Medical University Medical Center East), Dr. Yasuhiro Tanaka (Nishi Kobe Medical Center), Dr. Hiroki Yamaguchi (Nippon Medical School Hospital), Dr. Masaya Mukai (Sapporo City General Hospital), Dr. Yuichi Hasegawa (University of Tsukuba Hospital), Dr. Fumi Mizorogi (The Jikei University Daisan Hospital), Dr. Yoshitsugu Kubota (Mitoyo General Hospital), Dr. Tatsuya Adachi (Chukyo Hospital), Dr. Kazuhiko Ikeda (Fukushima Medical University), Dr. Yuka Takada (Kurume University), and Dr. Koh Yamamoto (Yokohama City Minato Red Cross Hospital) for their invaluable contribution to the data.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.


  1. 1.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, IARC Press; 2008Google Scholar
  2. 2.
    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
  3. 3.
    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
  4. 4.
    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
  5. 5.
    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
  6. 6.
    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
  7. 7.
    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.CrossRefPubMedGoogle Scholar
  8. 8.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Edahiro Y, Morishita S, Takahashi K, Hironaka Y, Yahata Y, et al. JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan. Int J Hematol. 2014;99(5):625–34.CrossRefPubMedGoogle Scholar
  10. 10.
    Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM, et al. The myeloproliferative neoplasm symptom assessment form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood. 2011;118(2):401–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Martinez-Trillos A, Gaya A, Maffioli M, Arellano-Rodrigo E, Calvo X, Diaz-Beya M, et al. Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients. Ann Hematol. 2010;89(12):1233–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Elliott MA, Chen MG, Silverstein MN, Tefferi A. Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia. Br J Haematol. 1998;103(2):505–11.CrossRefPubMedGoogle Scholar
  13. 13.
    Jaffe ES, Harris NL, Stein H, Vardiman JW. Tumours of haematopoietic and lymphoid tissues. Lyon, IARC Press; 2001Google Scholar
  14. 14.
    Shimoda K, Shide K, Kamezaki K, Okamura T, Harada N, Kinukawa N, et al. The effect of anabolic steroids on anemia in myelofibrosis with myeloid metaplasia: retrospective analysis of 39 patients in Japan. Int J Hematol. 2007;85(4):338–43.CrossRefPubMedGoogle Scholar
  15. 15.
    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.CrossRefPubMedGoogle Scholar
  16. 16.
    Bouabdallah R, Coso D, Gonzague-Casabianca L, Alzieu C, Resbeut M, Gastaut JA. Safety and efficacy of splenic irradiation in the treatment of patients with idiopathic myelofibrosis: a report on 15 patients. Leuk Res. 2000;24(6):491–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807.CrossRefPubMedGoogle Scholar
  18. 18.
    Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787–98.CrossRefPubMedGoogle Scholar
  19. 19.
    Ogama Y, Mineyama T, Yamamoto A, Woo M, Shimada N, et al. A randomized dose-escalation study to assess the safety, tolerability, and pharmacokinetics of ruxolitinib (INC424) in healthy Japanese volunteers. Int J Hematol. 2013;97(3):351–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Oritani K, Okamoto S, Tauchi T, Saito S, Ohishi K, et al. A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis. Int J Hematol. 2015;101(3):295–304.CrossRefPubMedGoogle Scholar
  21. 21.
    Mascarenhas J, Hoffman R. A comprehensive review and analysis of the effect of ruxolitinib therapy on the survival of patients with myelofibrosis. Blood. 2013;121(24):4832–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Passamonti F, Maffioli M, Cervantes F, Vannucchi AM, Morra E, Barbui T, et al. Impact of ruxolitinib on the natural history of primary myelofibrosis: a comparison of the DIPSS and the COMFORT-2 cohorts. Blood. 2014;123(12):1833–5.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  • Akira Kitanaka
    • 1
  • Katsuto Takenaka
    • 2
  • Kotaro Shide
    • 1
  • Toshihiro Miyamoto
    • 2
  • Tadakazu Kondo
    • 3
  • Keiya Ozawa
    • 4
  • Mineo Kurokawa
    • 5
  • Koichi Akashi
    • 2
  • Kazuya Shimoda
    • 1
    Email author
  1. 1.Department of Gastroenterology and Hematology, Faculty of MedicineUniversity of MiyazakiKiyotakeJapan
  2. 2.Department of Medicine and Biosystemic ScienceKyushu University Graduate School of Medical ScienceFukuokaJapan
  3. 3.Department of Hematology and Oncology, Graduate School of MedicineKyoto UniversityKyotoJapan
  4. 4.The Institute of Medical ScienceThe University of TokyoTokyoJapan
  5. 5.Department of Hematology and Oncology, Graduate School of MedicineThe University of TokyoTokyoJapan

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