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Danazol therapy for the anemia of myelofibrosis: assessment of efficacy with current criteria of response and long-term results

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Abstract

The efficacy of danazol was assessed in 50 patients with myelofibrosis and anemia using the recently revised criteria of the International Working Group for Myelofibrosis Research and Treatment. According to them, anemia response (clinical improvement) is defined as transfusion cessation in transfusion-dependent patients or an Hb increase >2 g/dl in patients without transfusion requirements, both maintained for at least 12 weeks. Median follow-up from danazol start was 36 months (interquartile range [IQR] 19.2–58.8). Anemia response was achieved in 15 patients (30 %), including 5 of the 27 with transfusion dependency (18.5 %) and 10 of the 23 without transfusion requirements (43.5 %). Median time to response was 5 months (IQR 4–7) and median duration of the response 14 months (IQR 10–21). Among responder patients, 5 discontinued therapy due to toxicity or personal decision and 1 died from spleen rupture while being in response. A trend for worse response was seen in transfusion-dependent patients (p = 0.055). A platelet increase >50 × 109/l was observed in 3 of 13 thrombocytopenic patients, all of whom had moderate thrombocytopenia. Toxicity was usually moderate, leading to treatment withdrawal in only 4 patients. Danazol is effective in 30 % of patients with anemia-associated myelofibrosis. The responses are less frequent in patients with transfusion dependency.

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References

  1. Tefferi A (2000) Myelofibrosis with myeloid metaplasia. N Engl J Med 342:1255–1265

    Article  CAS  PubMed  Google Scholar 

  2. Cervantes F (2014) How I treat myelofibrosis. Blood 124:2635–2642

    Article  CAS  PubMed  Google Scholar 

  3. Tefferi A, Passamonti F, Barbui T, Barosi G, Begna K, Cazzola M, Cervantes F, Döhner K, Gisslinger H, Gupta V, Li W, Harrison CN, Kiladjian JJ, McMullin MF, Rambaldi A, Schiller GJ, Vannucchi AM, Mesa RA (2013) Phase 3 study of pomalidomide in myeloproliferative neoplasm (MPN)-associated myelofibrosis with RBC-transfusion dependence (abstract). Blood 122:394

    Article  Google Scholar 

  4. Tefferi A, Cervantes F, Mesa R, Passamonti F, Verstovsek S, Vannucchi AM, Gotlib J, Dupriez B, Pardanani A, Harrison C, Hoffman R, Gisslinger H, Kroger N, Thiele J, Barbui T, Barosi G (2013) Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood 122:1395–1398

    Article  CAS  PubMed  Google Scholar 

  5. Cervantes F, Alvarez-Larrán A, Domingo A, Arellano-Rodrigo E, Montserrat E (2005) Efficacy and tolerability of danazol as a treatment for the anaemia of myelofibrosis with myeloid metaplasia: long-term results in 30 patients. Br J Haematol 129:771–775

    Article  CAS  PubMed  Google Scholar 

  6. Tefferi A, Thiele J, Orazi A, Kvasnicka HM, Barbui T, Hanson CA, Barosi G, Verstovsek S, Birgegard G, Mesa R, Reilly JT, Gisslinger H, Vannucchi AM, Cervantes F, Finazzi G, Hoffman R, Gilliland DG, Bloomfield CD, Vardiman JW (2007) Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 110:1092–1097

    Article  CAS  PubMed  Google Scholar 

  7. Barosi G, Mesa RA, Thiele J, Cervantes F, Campbell PJ, Verstovsek S, Dupriez B, Levine RL, Passamonti F, Gotlib J, Reilly JT, Vannucchi AM, Hanson CA, Solberg LA, Orazi A, Tefferi A (2008) Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia 22:438–439

    Article  Google Scholar 

  8. Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A (2005) European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 90:1128–1132

    PubMed  Google Scholar 

  9. Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, Vannucchi AM, Mesa RA, Demory JL, Barosi G, Rumi E, Tefferi A (2009) New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 113:2895–2901

    Article  CAS  PubMed  Google Scholar 

  10. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, Guglielmelli P, Pungolino E, Caramella M, Maffioli M, Pascutto C, Lazzarino M, Cazzola M, Tefferi A (2010) 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 115:1703–1708

    Article  CAS  PubMed  Google Scholar 

  11. Reilly JT (1998) Pathogenesis and management of idiopathic myelofibrosis. Baillière’s Clin Hematol 11:751–767

    Article  CAS  Google Scholar 

  12. Martínez-Trillos A, Gaya A, Maffioli M, Arellano-Rodrigo E, Calvo X, Díaz-Beyá M, Cervantes F (2010) Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients. Ann Hematol 89:1233–1237

    Article  PubMed  Google Scholar 

  13. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G (2012) JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 366:787–798

    Article  CAS  PubMed  Google Scholar 

  14. Cervantes F, Alvarez-Larrán A, Hernández-Boluda JC, Sureda A, Torrebadell M, Montserrat E (2004) Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature. Br J Haematol 127:399–403

    Article  CAS  PubMed  Google Scholar 

  15. Cervantes F, Alvarez-Larrán A, Hernández-Boluda JC, Sureda A, Granell M, Vallansot R, Besses C, Montserrat E (2006) Darbepoetin-alpha for the anaemia of myelofibrosis with myeloid metaplasia. Br J Haematol 134:184–186

    Article  CAS  PubMed  Google Scholar 

  16. Tsiara SN, Chaidos A, Bourantas LJ, Kapsali HD, Bourantas KL (2007) Recombinant human erythropoietin for the treatment of anemia in patients with idiopathic myelofibrosis. Acta Haematol 11:156–161

    Article  Google Scholar 

  17. Huang J, Tefferi A (2009) Erythropoiesis stimulating agents have limited therapeutic activity in transfusion-dependent patients with primary myelofibrosis regardless of serum erythropoietin level (letter). Eur J Haematol 83:154–155

    Article  CAS  PubMed  Google Scholar 

  18. Mesa RA, Steensma DP, Pardanani A, Li CY, Elliott M, Kaufmann SH, Wiseman G, Gray LA, Schroeder G, Reeder T, Zeldis JB, Tefferi A (2003) A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia. Blood 101:2534–2541

    Article  CAS  PubMed  Google Scholar 

  19. Mesa RA, Yao X, Li CY, Litzow M, Paietta E, Rowe JM, Tefferi A, Tallman MS (2010) Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903. Blood 116:4436–4438

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Quintás-Cardama A, Kantarjian HM, Manshouri T, Thomas D, Cortes J, Ravandi F, Garcia-Manero G, Ferrajoli A, Bueso-Ramos C, Verstovsek S (2009) Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis. J Clin Oncol 27:4760–4766

    Article  PubMed  Google Scholar 

  21. Tefferi A, Mesa RA, Nagomey DN, Schroeder G, Silverstein MN (2000) Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood 95:2226–2233

    CAS  PubMed  Google Scholar 

  22. Hast R, Engstedt L, Jameson S, Killander A, Lundh B, Reizenstein P, Skarberg KO, Udén AM, Wadman B (1978) Oxymetholone treatment in myelofibrosis. Blut 37:19–26

    Article  CAS  PubMed  Google Scholar 

  23. Brubaker LH, Brière J, Laszlo J, Kraut E, Landaw SA, Peterson P, Goldberg J, Donovan P (1982) Treatment of anemia in myeloproliferative disorders: a randomized study of fluoxymesterone v transfusions only. Arch Intern Med 142:1533–1537

    Article  CAS  PubMed  Google Scholar 

  24. Tefferi A, Verstovsek S, Barosi G, Passamonti F, Roboz GJ, Gisslinger H, Paquette RL, Cervantes F, Rivera CE, Deeg HJ, Thiele J, Kvasnicka HM, Vardiman JW, Zhang Y, Bekele BN, Mesa RA, Gale RP, Kantarjian HM (2009) Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol 27:4563–4569

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by grant RD12/0036/0010 from the Instituto de Salud Carlos III, Spanish Ministry of Health.

Authorship contributions

Francisco Cervantes designed the research, interpreted the results, and wrote the manuscript. Ignacio M. Isola, Juan-Gonzalo Correa, Alberto Alvarez-Larrán, and Juan-Carlos Hernández-Boluda collected the data, revised the manuscript, and approved its final version. Arturo Pereira performed the statistical analysis, interpreted the results, and revised the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain

    Francisco Cervantes, Ignacio M. Isola, Juan-Gonzalo Correa & Arturo Pereira

  2. Hematology Department, Hospital del Mar, Barcelona, Spain

    Alberto Alvarez-Larrán

  3. Hematology and Medical Oncology Department, Hospital Clínico Universitario, Valencia, Spain

    Juan-Carlos Hernández-Boluda

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  1. Francisco Cervantes
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  2. Ignacio M. Isola
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  3. Alberto Alvarez-Larrán
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  4. Juan-Carlos Hernández-Boluda
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  5. Juan-Gonzalo Correa
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  6. Arturo Pereira
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Correspondence to Francisco Cervantes.

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Cervantes, F., Isola, I.M., Alvarez-Larrán, A. et al. Danazol therapy for the anemia of myelofibrosis: assessment of efficacy with current criteria of response and long-term results. Ann Hematol 94, 1791–1796 (2015). https://doi.org/10.1007/s00277-015-2435-7

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  • DOI: https://doi.org/10.1007/s00277-015-2435-7

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