bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.18821/0234-5730-2017-62-4-229-232bloodjour-675Research ArticleКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯCASE REPORTSТерапия истинной полицитемии руксолитинибомTherapy of polycythemia vera with ruxolithinibhttps://orcid.org/0000-0002-2119-3775МеликянА. Л.MelikyanA. L.

Меликян Анаит Левоновна, доктор медицинских наук, заведующая отделением стандартизации методов лечения

125167, г. Москва

Melikyan Anait L., MD, PhD, Head of the Department of Standardization of Methods of Treatment

Moscow, 125167

anoblood@mail.ruhttps://orcid.org/0000-0001-9045-8653СуборцеваИ. Н.SubortsevaI. N.

125167, г. Москва

Moscow, 125167

https://orcid.org/0000-0002-3883-185XГилязитдиноваЕ. А.GilyazitdinovaE. A.

125167, г. Москва

Moscow, 125167

https://orcid.org/0000-0002-1082-8659КовригинаА. М.KovriginaA. M.

125167, г. Москва

Moscow, 125167

https://orcid.org/0000-0001-9463-9187СудариковА. Б.SudarikovA. B.

125167, г. Москва

Moscow, 125167

https://orcid.org/0000-0003-2530-808XАбдуллаевА. О.AbdullaevА. O.

125167, г. Москва

Moscow, 125167

ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава РоссииРоссияNational Research Center for HematologyRussian Federation201717102025624229232Copyright © Меликян А.Л., Суборцева И.Н., Гилязитдинова Е.А., Ковригина А.М., Судариков А.Б., Абдуллаев А.О., 20252025Меликян А.Л., Суборцева И.Н., Гилязитдинова Е.А., Ковригина А.М., Судариков А.Б., Абдуллаев А.О.Melikyan A.L., Subortseva I.N., Gilyazitdinova E.A., Kovrigina A.M., Sudarikov A.B., Abdullaev А.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/675

В настоящее время методами воздействия при истинной полицитемии (ИП) являются: профилактика тромботических осложнений (препараты ацетилсалициловой кислоты); физическое удаление избыточной массы циркулирующих эритроцитов (кровопускание или эритроцитаферез); циторедуктивная терапия; лечение тромботических осложнений; терапия в особых ситуациях (при беременности, хирургических вмешательствах). В качестве 1-й линии лечения в молодом возрасте показан интерферон α, в старшей возрастной группе – гидроксикарбамид. В 15–25% случаев данные препараты имеют малую эффективность и плохую переносимость. Переход на другую линию показан в случае неэффективности или непереносимости проводимой терапии. Результаты клинических исследований доказали эффективность ингибитора JAK2 руксолитиниба в купировании массивной спленомегалии и конституциональных симптомов у больных первичным миелофиброзом и ИП. Представлен обзор литературы и описание клинического случая эффективного лечения больного ИП руксолитинибом.

Currently, methods of therapeutic the treatment of polycythemia vera (PV) are: prophylaxis of thrombotic complications with acetylsalicylic acid; erythrocytapheresis; cytoreductive therapy; treatment of thrombotic complications; therapy in special conditions  (pregnancy, surgery). The first line of the treatment at a young age is interferon α, in the older age group is hydroxycarbamide. In 15–25% of cases, these drugs have low efficiency and poor tolerance. The transition to another line is indicated if the therapy is ineffective or patient is intolerant of the therapy. Results of clinical trials have proved the effectiveness of ruxolitinib,  JAK2 inhibitor,  in the management of splenomegaly and constitutional symptoms in patients with primary myelofibrosis and PV. A review of the literature and a description of the clinical case of the effective treatment of the PV patient ruxolitinib is presented. 

миелопролиферативные неоплазииистинная полицитемияJAK2V617Fруксолитинибmyeloproliferative neoplasiatrue polycythemiaJAK2V617FruxolitinibReferencesМеликян А.Л., Туркина А.Г., Абдулкадыров К.М., Зарицкий А.Ю., Афанасьев Б.В., Шуваев В.А. и др. Клинические рекомендации по диагностике и терапии Ph-негативных миелопролиферативных заболеваний (истинная полицитемия, эссенциальная тромбоцитемия, первичный миелофиброз). Гематология и трансфузиология. 2014; 59(4): 31–56.Melikyan A.L., Turkina A.G., Abdulkadyrov K.M., Zarickij A.YU., Afanas’ev B.V., SHuvaev V.A. et al. Clinical recommendations for the diagnosis and therapy of Ph-negative myeloproliferative diseases (true polycythemia, essential thrombocythemia, primary myelofibrosis). Russian Journal of Hematology and Transfusiology (Gematologiya i transfusiologiya). 2014; 59(4): 31–56. (in Russian)Меликян А.Л., Суборцева И.Н. Миелопролиферативные новообразования: новые данные. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2016; 9(2): 218–28.Melikyan A.L., Suborceva I.N. Myeloproliferative neoplasms: new data. Russian Journal of Clinical oncohematology. Fundamental research and clinical practice (Klinicheskaya onkogematologiya. Fundamentalnye issledovaniya i klinicheskaya praktika).. 2016; 9(2): 218–28. (in Russian)Mehta J., Wang H., Iqbal S.U., Mesa R. Epidemiology of myeloproliferativevneoplasms in the United States. Leuk. Lymphoma. 2014; 55(3): 595–600.Mehta J., Wang H., Iqbal S.U., Mesa R. Epidemiology of myeloproliferativevneoplasms in the United States. Leuk. Lymphoma. 2014; 55(3): 595–600.Saliba J., Saint-Martin C., Di Stefano A., Lenglet G., Marty C., Keren B., et al. Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies. Nat. Genet. 2015; 47(10): 1131–40.Saliba J., Saint-Martin C., Di Stefano A., Lenglet G., Marty C., Keren B., et al. Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies. Nat. Genet. 2015; 47(10): 1131–40.Меликян А.Л., Суборцева И.Н. Материалы 58-й ежегодной конференции Американского гематологического общества (декабрь 2016 г. Сан-Диего). Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2017; 10(2): 258–70.Melikyan A.L., Suborceva I.N. Materials of the 58th Congress of the American Hematology Society (December 2016, San Diego). Russian Journal of Clinical Oncohematology. Fundamental research and clinical practice (Klinicheskaya onkogematologiya. Fundamentalnye issledovaniya i klinicheskaya praktika). 2017; 10(2): 258–70. (in Russian)Tefferi A., Rumi E., Finazzi G., Gisslinger H., Vannucchi A.M., Rodeghiero F., Randi M.L., et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013; 27(9): 1874–81.Tefferi A., Rumi E., Finazzi G., Gisslinger H., Vannucchi A.M., Rodeghiero F., Randi M.L., et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013; 27(9): 1874–81.Marchioli R., Finazzi G., Landolfi R., Kutti J., Gisslinger H., Patrono C., et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J. Clin. Oncol. 2005; 23(10): 2224–32.Marchioli R., Finazzi G., Landolfi R., Kutti J., Gisslinger H., Patrono C., et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J. Clin. Oncol. 2005; 23(10): 2224–32.Меликян А.Л., Суборцева И.Н. Материалы 19-го конгресса Европейской гематологической ассоциации (2014 г., Милан). Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2014; 7(4): 598–607.Melikyan A.L., Suborceva I.N. Materials of the 19th Congress of the European Hematology Association (2014, Milan). Russian Journal of Clinical Oncohematology. Fundamental research and clinical practice (Klinicheskaya onkogematologiya. Fundamentalnye issledovaniya i klinicheskaya praktika). 2014; 7(4): 598–607. (in Russian).Меликян А.Л., Суборцева И.Н. Материалы 56-го конгресса Американского гематологического общества (декабрь 2014 г., Сан-Франциско). Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2015; 8(2): 201–32.Melikyan A.L., Suborceva I.N. Materials of the 56th Congress of the American Hematology Society (December 2014, San Francisco). Russian Journal of Clinical Oncohematology. Fundamental research and clinical practice (Klinicheskaya onkogematologiya. Fundamentalnye issledovaniya i klinicheskaya praktika). 2015; 8(2): 201–32. (in Russian)Суборцева И.Н., Колошейнова Т.И., Пустовая Е.И., Егорова Е.К., Ковригина А.М., Плискунова Ю.В. и др. Истинная полицитемия: обзор литературы и собственные данные. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2015; 8(4): 397–412.Subortseva I.N., Kolosheynova T.I., Pustovaya E.I., Egorova E.K., Kovrigina A.M., Pliskunova Yu.V., et al. Polycythemia vera: a review of literature and our own data. Russian Journal of Clinical Oncohematology. Fundamental research and clinical practice (Klinicheskaya onkogematologiya. Fundamentalnye issledovaniya i klinicheskaya praktika). 2015; 8(4): 397–412. (in Russian)Subortseva I.N., Kolosheinova T.I., Pustovaya E.I., Egorova E.K., Kovrigina A.M., Pliskunova Yu.V., et al. Diagnosis and treatment of polycythemia vera (PV) in Russian Federation: single center experience. Blood. 2015; 126(23): 5196.Subortseva I.N., Kolosheinova T.I., Pustovaya E.I., Egorova E.K., Kovrigina A.M., Pliskunova Yu.V., et al. Diagnosis and treatment of polycythemia vera (PV) in Russian Federation: single center experience. Blood. 2015; 126(23): 5196.Emanuel R.M., Dueck A.C., Geyer H.L., Kiladjian J.J., Slot S., Zweegman S., et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J. Clin. Oncol. 2012; 30(33): 4098–103.Emanuel R.M., Dueck A.C., Geyer H.L., Kiladjian J.J., Slot S., Zweegman S., et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J. Clin. Oncol. 2012; 30(33): 4098–103.Tefferi A., Elliott M. Thrombosis in myeloproliferative disorders: prevalence, prognostic factors, and the role of leukocytes and JAK2V617F. Semin. Thromb. Hemost. 2007; 33(4): 313–20.Tefferi A., Elliott M. Thrombosis in myeloproliferative disorders: prevalence, prognostic factors, and the role of leukocytes and JAK2V617F. Semin. Thromb. Hemost. 2007; 33(4): 313–20.Marchioli R., Finazzi G., Specchia G., Cacciola R., Cavazzina R., Cilloni D., et al.; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N. Engl. J. Med. 2013; 368(1): 22–33.Marchioli R., Finazzi G., Specchia G., Cacciola R., Cavazzina R., Cilloni D., et al.; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N. Engl. J. Med. 2013; 368(1): 22–33.Kremyanskaya M., Mascarenhas J., Hoffman R. Anagrelide hydrochloride and ruxolitinib for treatment of polycythemia vera. Expert. Opin. Pharmacother. 2015; 16(8): 1185–94.Kremyanskaya M., Mascarenhas J., Hoffman R. Anagrelide hydrochloride and ruxolitinib for treatment of polycythemia vera. Expert. Opin. Pharmacother. 2015; 16(8): 1185–94.Landolfi R., Marchioli R. European collaboration on low-dose aspirin in polycythemia vera (ECLAP): a randomized trial. Semin. Thromb. Hemost. 1997; 23(5): 473–8.Landolfi R., Marchioli R. European collaboration on low-dose aspirin in polycythemia vera (ECLAP): a randomized trial. Semin. Thromb. Hemost. 1997; 23(5): 473–8.Landolfi R., Marchioli R., Kutti J., Gisslinger H., Tognoni G., Patrono C., Barbui T. Efficacy and safety of low-dose aspirin in polycythemia vera. N. Engl. J. Med. 2004; 350(2): 114–24.Landolfi R., Marchioli R., Kutti J., Gisslinger H., Tognoni G., Patrono C., Barbui T. Efficacy and safety of low-dose aspirin in polycythemia vera. N. Engl. J. Med. 2004; 350(2): 114–24.Суборцева И.Н., Меликян А.Л., Ковригина А.М., Судариков А.Б. Латентная истинная полицитемия. Гематология и трансфузиология. 2016; 61(1, прил. 1): 72.Suborceva I.N., Melikyan A.L., Kovrigina A.M., Sudarikov A.B. Latent polycythemia vera. Russian Journal of Hematology and transfusiology (Gematologiya i transfusiologiya). 2016; 61(1, Suppl. 1): 72. (in Russian)Silver R.T. Long-Term effects of the treatment of polycythemia vera with recombinant IFNα. Cancer. 2006; 107(3): 451–8.Silver R.T. Long-Term effects of the treatment of polycythemia vera with recombinant IFNα. Cancer. 2006; 107(3): 451–8.Najean Y. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997; 90(9): 3370–7.Najean Y. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997; 90(9): 3370–7.Cortelazzo S., Finazzi G., Ruggeri M. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N. Engl. J. Med. 1995; 332(17): 1132–6.Cortelazzo S., Finazzi G., Ruggeri M. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N. Engl. J. Med. 1995; 332(17): 1132–6.Quintas-Cardama A., Kantarjian H., Manshouri T., Luthra R., Estrov Z., Pierce S., et al. Pegylated interferon α2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J. Clin. Oncol. 2009; 27(32): 5418–24.Quintas-Cardama A., Kantarjian H., Manshouri T., Luthra R., Estrov Z., Pierce S., et al. Pegylated interferon α2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J. Clin. Oncol. 2009; 27(32): 5418–24.Tefferi A. The history of myeloproliferative disorders: before and after Dameshek. Leukemia. 2008; 22(1): 3–13. doi:10.1038/sj.leu.2404946Tefferi A. The history of myeloproliferative disorders: before and after Dameshek. Leukemia. 2008; 22(1): 3–13. doi:10.1038/sj.leu.2404946Меликян А.Л., Суборцева И.Н. биология миелопролиферативных новообразований. Клиническая онкогематология. Фундаментальные исследования и клиническая практика. 2016; 9(3): 314–25.Melikyan A.L., Subortseva I.N. Biology of myeloproliferative diseases. Russian Journal of Clinical Oncohematology. Fundamental research and clinical practice (Klinicheskaya onkogematologiya. Fundamentalnye issledovaniya i klinicheskaya praktika). 2016; 9(3): 314–25. doi: 10.1182/blood-2009-03-209262. (in Russian)Quintas-Cardama A., Vaddi K., Liu P., Vestri O., Galli M., Rodeghiero F., Barbui T. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010; 115(15): 3109–17.Quintas-Cardama A., Vaddi K., Liu P., Vestri O., Galli M., Rodeghiero F., Barbui T. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010; 115(15): 3109–17.Vannucchi A.M., Kiladjian J.J., Griesshammer M., Masszi T., Durrant S., Passamonti F., et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N. Engl. J. Med. 2015; 372(5): 426–35.Vannucchi A.M., Kiladjian J.J., Griesshammer M., Masszi T., Durrant S., Passamonti F., et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N. Engl. J. Med. 2015; 372(5): 426–35.Cervantes F., Vannucchi A.M., Kiladjian J.J., Al-Ali H.K., Sirulnik A., Stalbovskaya V., et al.; COMFORT-II investigators. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013; 122(25): 4047–53.Cervantes F., Vannucchi A.M., Kiladjian J.J., Al-Ali H.K., Sirulnik A., Stalbovskaya V., et al.; COMFORT-II investigators. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013; 122(25): 4047–53.Mesa R., Vannucchi A.M., Yacoub A., Zachee P., Garg M., Lyons R., et al. The efficacy and safety of continued hydroxyurea therapy versus switching to ruxolitinib in patients with polycythemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF). Br. J. Haematol. 2017; 176(1): 76–85. doi:10.1111/bjh.14382.Mesa R., Vannucchi A.M., Yacoub A., Zachee P., Garg M., Lyons R., et al. The efficacy and safety of continued hydroxyurea therapy versus switching to ruxolitinib in patients with polycythemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF). Br. J. Haematol. 2017; 176(1): 76–85. doi:10.1111/bjh.14382.Alvarez-Larrán A., Kerguelen A., Hernández-Boluda J.C., Pérez-Encinas M., Ferrer-Marín F., Bárez A., et al. Frequency and prognostic value of resistance/ intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. Br. J. Haematol. 2016; 172(5): 786–93.Alvarez-Larrán A., Kerguelen A., Hernández-Boluda J.C., Pérez-Encinas M., Ferrer-Marín F., Bárez A., et al. Frequency and prognostic value of resistance/ intolerance to hydroxycarbamide in 890 patients with polycythaemia vera. Br. J. Haematol. 2016; 172(5): 786–93.Antonioli E., Guglielmelli P., Pieri L., Finazzi M., Rumi E., Martinelli V., et al. Hydroxyurea-related toxicity in 3,411 patients with Ph-negative MPN. Am. J. Hematol. 2012; 87(5): 552–4.Antonioli E., Guglielmelli P., Pieri L., Finazzi M., Rumi E., Martinelli V., et al. Hydroxyurea-related toxicity in 3,411 patients with Ph-negative MPN. Am. J. Hematol. 2012; 87(5): 552–4.Instructions for the use of the drug Jakavi® No. LP 002028, issued by the Ministry of Health of the Russian Federation of 21.03.2013. Available at: https://www.rlsnet.ru/tn_index_id_58405.htm (Access 06 Apr 2017)Instructions for the use of the drug Jakavi® No. LP 002028, issued by the Ministry of Health of the Russian Federation of 21.03.2013. Available at: https://www.rlsnet.ru/tn_index_id_58405.htm (Access 06 Apr 2017)Bjorkholm M., Derolf A.R., Hultcrantz M., Kristinsson S.Y., Ekstrand C., Goldin L.R., et al. Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms. J. Clin. Oncol. 2011; 29(17): 2410–5.Bjorkholm M., Derolf A.R., Hultcrantz M., Kristinsson S.Y., Ekstrand C., Goldin L.R., et al. Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms. J. Clin. Oncol. 2011; 29(17): 2410–5.Verstovsek S., Vannucchi A.M., Griesshammer M., Masszi T., Durrant S., Passamonti F., et al. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016; 101(7): 821–9. doi: 10.3324/haematol.2016.143644Verstovsek S., Vannucchi A.M., Griesshammer M., Masszi T., Durrant S., Passamonti F., et al. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016; 101(7): 821–9. doi: 10.3324/haematol.2016.143644Танашян М.М., Кузнецова П.И., Лагода О.В., Шабалина А.А., Суборцева И.Н., Меликян А.Л. Миелопролиферативные заболевания и ишемический инсульт. Анналы клинической и экспериментальной неврологии. 2014; 8(2): 41–5.Tanashyan M.M., Kuznecova P.I., Lagoda O.V., SHabalina A.A., Suborceva I.N., Melikyan A.L. Myeloproliferative diseases and ischemic stroke. Annals of clinical and experimental neurology. Russian Journal (Annaly klinicheskoy i eksperimentalnoy nevrologii). 2014; 8(2): 41–5. (in Russian)Меликян А.Л., Суборцева И.Н., Суханова Г.А. Тромбогеморрагические осложнения у больных Ph-негативными миелопролиферативными заболеваниями. Кровь. 2014; 2(1): 21–5.Melikyan A.L., Subortceva I.N., Suhanova G.A. Thrombohemorrhagic complications in patients with Ph-negative myeloproliferative diseases. Russian Journal “Blood” (Krov’). 2014; 2(1): 21–5. (in Russian)Samuelson B.T., Vesely S.K., Chai-Adisaksopha C., Scott B.L., Crowther M., Garcia D. The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis. Blood Coagul. Fibrinolysis. 2016; 27(6): 648–52. doi: 10.1097/MBC.0000000000000446.Samuelson B.T., Vesely S.K., Chai-Adisaksopha C., Scott B.L., Crowther M., Garcia D. The impact of ruxolitinib on thrombosis in patients with polycythemia vera and myelofibrosis: a meta-analysis. Blood Coagul. Fibrinolysis. 2016; 27(6): 648–52. doi: 10.1097/MBC.0000000000000446.

The authors declare that there are no conflicts of interest present.