bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.25837/HAT.2018.26..1..003bloodjour-84Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESРЕЗУЛЬТАТЫ ТЕРАПИИ ИМАТИНИБОМ У БОЛЬНЫХ ХРОНИЧЕСКИМ МИЕЛОЛЕЙКОЗОМ В НАЦИОНАЛЬНОМ ИНСТИТУТЕ ГЕМАТОЛОГИИ И ТРАНСФУЗИОЛОГИИ ВЬЕТНАМАRESULT OF THE TREATMENT OF CHRONIC MYELOID LEUKEMIA WITH IMATINIB FROM THE VIETNAM NATIONAL INSTITUTE OF HEMATOLOGY AND BLOOD TRANSFUSIONhttps://orcid.org/0000-0002-4884-0522ТханьНгуен ХаThanhNguyen Ha

Нгуен Ха Тхань, доцент, отделение химио-терапии

Nguyen Ha Thanh, associate professor, Department of Chemotherapy, National Institute of Hematology and Blood Transfusion

ha_thanh_nguyen_vhhtm@yahoo.comЧиНгуен АньTriNguyen Anh

ID 044057000041

ID 044057000041

ТхаоНгуен ТхиThaoNguyen Thi

ID 013132321

ID 013132321

Хай,Ле СуанHaiLe Xuan

ID 001071006372

ID 001071006372

ХуонгВу Тхи БитьHuongVu Thi Bich

ID 001179017747

ID 001179017747

ТиньДуонг КуокChinhDuong Quoc

ID 012179370

ID 012179370

КханьБать КуокKhanhBach Quoc

ID 011020509

ID 011020509

Национальный институт гематологии и трансфузиологии, ХанойВьетнамNational Institute of Hematology and Blood Transfusion, HanoiViet Nam2018180420196313143Copyright © Тхань Н.Х., Чи Н.А., Тхао Н.Т., Хай, Л.С., Хуонг В.Б., Тинь Д.К., Кхань Б.К., 20192019Тхань Н.Х., Чи Н.А., Тхао Н.Т., Хай, Л.С., Хуонг В.Б., Тинь Д.К., Кхань Б.К.Thanh N.H., Tri N.A., Thao N.T., Hai L.X., Huong V.B., Chinh D.Q., Khanh B.Q.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/84Введение

Введение. Хронический миелолейкоз (ХМЛ) является распространенной патологией во Вьетнаме, занимая третье место в структуре злокачественных заболеваний крови. С 2009 г. во Вьетнаме в качестве стартовой терапии больных ХМЛ применяется иматиниб, эффективность которого была оценена в данном исследовании.

Материалы и методы

Материалы и методы. Проведен анализ результатов терапии иматинибом (400 мг/сут) у больных ХМЛ (n = 121), находившихся на лечении в Национальном институте гематологии и трансфузиологии Вьетнама в 2010—2014 гг.

Результаты

Результаты. На фоне терапии иматинибом кумулятивная частота полного цитогенетического ответа составила 67,8%, полного молекулярного ответа — 66,1%. Установлена корреляция между продолжительностью периода времени от установки диагноза ХМЛ до начала лечения иматинибом, с одной стороны, и частотой достижения полного цитогенетического ответа (отношение рисков 0,158; p= 0,001) и полного молекулярного ответа (отношение рисков 0,263; p = 0,018), с другой стороны. Выявлено, что у больных ХМЛ применение иматиниба уменьшает влияние на течение заболевания установленных ранее прогностических факторов. Ежегодный риск прогрессии ХМЛ уменьшался со временем. Трехлетние показатели выживаемости без прогрессии заболевания и общей выживаемости составили 94,2 и 98% соответственно. Гематологические побочные эффекты легкой степени выраженности отмечены в течение первого года наблюдения: у 17 (14%) больных в виде анемии 1—2-й степени, у 27 (22,3%) — гранулоцитопении, у 29 (23,9%) — тромбоцитопении. Из негематологических побочных эффектов наиболее часто регистрировали периорбитальный отек, тошноту, сыпь, боли в мышцах и суставах.

Introduction

Introduction. Chronic myeloid leukemia (CML) ranks third among hematological malignancies in Vietnam. Imatinib has become the standard therapy for CML patients in Vietnam since 2009.

Materials and methods

Materials and methods. A phase IV clinical study for 1st line imatinib treatment of CML patients, carried out in 121 CML patients treated in NIHBT and receiving imatinib 400 mg/daily from 2010 to 2014.

Results

Results. Cumulative CCyR and CMR were achieved in 82 (67.8%) and 80 (66.1%) of patients, respectively. There was a correlation between the time interval (from CML diagnosis to initiating imatinib treatment) and both complete cytogenetic (OR 0.158; p = 0.001) and molecular (OR 0.263; p = 0.018) responses. The analysis demonstrated that imatinib treatment minimized the prognostic impact of previously established prognostic factors in CML. The 3-year PFS and OS rates were 114 (94.6%) and 118 (97.5%), respectively. Hematologic adverse effects were mild with 1st and 2nd grades anemia, granulocytopenia and thrombocytopenia found in 17 (14%), 27 (22.3%) and 29 (23.9%) patients, respectively. The most commonly non-hematologic adverse effects occurred in 1st year of follow-up including periorbital edema, nausea, musculoskeletal pain, and rash.

хронический миелолейкозиматинибцитогене-тический ответмолекулярный ответвыживаемостьchronic myeloid leukemiaimatinibcytogenetic responsemolecular responsesurvivalИсследование выполнено при частичной под-держке Департамента науки, технологии и повышения квалификации Министерства здравоохранения Вьетнама.This study was funded in part by the Department of Science, Technology and Training (the Ministry of Health of Vietnam).ReferencesBaccarani M, Deininger MW, Rosti G et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia 2013. Blood 2013; 122:872—884. doi: 10.1182/blood-2013-05-501569.Baccarani M, Deininger MW, Rosti G et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia 2013. Blood 2013; 122:872—884. doi: 10.1182/blood-2013-05-501569.Tran Thi Minh Huong, Do Trung Phan. Epidemiology of hematopoietic diseases in northern Vietnam according to statistics data from Institute of Hematology and Blood Transfusion, Bach Mai hospital. Annu Hematol Sci Res 2002; 8:15—24.Tran Thi Minh Huong, Do Trung Phan. Epidemiology of hematopoietic diseases in northern Vietnam according to statistics data from Institute of Hematology and Blood Transfusion, Bach Mai hospital. Annu Hematol Sci Res 2002; 8:15—24.Sokal JE, Cox EB, Baccarani M et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood 1984; 63:789—799.Sokal JE, Cox EB, Baccarani M et al. Prognostic discrimination in “good-risk” chronic granulocytic leukemia. Blood 1984; 63:789—799.Hughes TP, Hochhaus A, Branford S et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood 2010; 116:3758—3765. doi: 10.1182/blood-2010-03-273979.Hughes TP, Hochhaus A, Branford S et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood 2010; 116:3758—3765. doi: 10.1182/blood-2010-03-273979.Hanfstein B, Muller MC, Hehlmann R et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 2012; 26:2096—2102. doi:10.1038/leu.2012.85.Hanfstein B, Muller MC, Hehlmann R et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 2012; 26:2096—2102. doi:10.1038/leu.2012.85.Rousselot Ph, Guilhot J, Preudhomme C et al. Relationship between molecular responses and disease progression in patients treated first line with imatinib (Im) based regimens: impact of treatment arm within the French Spirit trial from the French CML group (FI LMC). Blood 2012; 120:168.Rousselot Ph, Guilhot J, Preudhomme C et al. Relationship between molecular responses and disease progression in patients treated first line with imatinib (Im) based regimens: impact of treatment arm within the French Spirit trial from the French CML group (FI LMC). Blood 2012; 120:168.Chavan D, Ahmad F, Iyer P et al. Cytogenetic investigation in chronic myeloid leukemia: study from an Indian population. Asian Pac J Cancer Prev 2006; 7:423—426.Chavan D, Ahmad F, Iyer P et al. Cytogenetic investigation in chronic myeloid leukemia: study from an Indian population. Asian Pac J Cancer Prev 2006; 7:423—426.Irfan SM, Bhurgri Y. Clinico-pathological features and outcomes in chronic phase chronic myeloid leukemia patients treated with hydroxyurea. Asian Pac J Cancer Prev 2009; 10:591—594.Irfan SM, Bhurgri Y. Clinico-pathological features and outcomes in chronic phase chronic myeloid leukemia patients treated with hydroxyurea. Asian Pac J Cancer Prev 2009; 10:591—594.Bhat G, Bhat A, Wani A et al. Polymorphic variation in glutathione-S-transferase genes and risk of chronic myeloid leukaemia in the Kashmiri population. Asian Pac J Cancer 2012; 13:69—73.Bhat G, Bhat A, Wani A et al. Polymorphic variation in glutathione-S-transferase genes and risk of chronic myeloid leukaemia in the Kashmiri population. Asian Pac J Cancer 2012; 13:69—73.Usmani SZ, Yunus SA, Jamal Y. Overview of chronic myeloid leukemia patients in Pakistan in the pre-imatanib era. Asian Pac J Cancer Prev 2009; 10:1039—1040.Usmani SZ, Yunus SA, Jamal Y. Overview of chronic myeloid leukemia patients in Pakistan in the pre-imatanib era. Asian Pac J Cancer Prev 2009; 10:1039—1040.Kantarjian H, O’Brien S, Jabbour E et al. Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood 2012; 119:1981—1987. doi: 10.1182/blood-2011-08-358135Kantarjian H, O’Brien S, Jabbour E et al. Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood 2012; 119:1981—1987. doi: 10.1182/blood-2011-08-358135Payandeh M, Sadeghi M, Sadeghi E. Treatment and survival in patients with chronic myeloid leukemia in a chronic phase in West Iran. Asian Pac J Cancer Prev 2015; 16:7555—7559.Payandeh M, Sadeghi M, Sadeghi E. Treatment and survival in patients with chronic myeloid leukemia in a chronic phase in West Iran. Asian Pac J Cancer Prev 2015; 16:7555—7559.Branford S, Seymour JF, Grigg A et al. BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR-ABL using strict sensitivity criteria. Clin Cancer Res 2007; 13:7080—7085. doi: 10.1158/1078-0432.CCR-07-0844.Branford S, Seymour JF, Grigg A et al. BCR-ABL messenger RNA levels continue to decline in patients with chronic phase chronic myeloid leukemia treated with imatinib for more than 5 years and approximately half of all first-line treated patients have stable undetectable BCR-ABL using strict sensitivity criteria. Clin Cancer Res 2007; 13:7080—7085. doi: 10.1158/1078-0432.CCR-07-0844.Druker BJ, Guilhot F, O’Brien SG et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355:2408—2417. doi: 10.1056/NEJMoa062867.Druker BJ, Guilhot F, O’Brien SG et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355:2408—2417. doi: 10.1056/NEJMoa062867.Hochhaus A, O’Brien SG, Guilhot F et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009; 23:1054—1061. doi:10.1038/leu.2009.38.Hochhaus A, O’Brien SG, Guilhot F et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009; 23:1054—1061. doi:10.1038/leu.2009.38.Kantarjian HM, O’Brien S, Cortes JE et al. Complete cytogenetic and molecular responses to interferon alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer 2003; 97:1033—1041. doi: 10.1002/cncr.11223.Kantarjian HM, O’Brien S, Cortes JE et al. Complete cytogenetic and molecular responses to interferon alpha-based therapy for chronic myelogenous leukemia are associated with excellent long-term prognosis. Cancer 2003; 97:1033—1041. doi: 10.1002/cncr.11223.Hehlmann R, Lauseker M, Jung-Munkwitz S et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon αin newly diagnosed chronic myeloid leukemia. J Clin Oncol 2011; 29:1634—1642. doi: 10.1200/JCO.2010.32.0598.Hehlmann R, Lauseker M, Jung-Munkwitz S et al. Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon αin newly diagnosed chronic myeloid leukemia. J Clin Oncol 2011; 29:1634—1642. doi: 10.1200/JCO.2010.32.0598.Payandeh M, Sadeghi E, Sadeghi M. Non-hematological adverse events of imatinib in patients with chronic myeloid leukemia in chronic phase (CML-CP). J App Pharm Sci 2015; 5:87—90. doi: 10.7324/JAPS.2015.50213.Payandeh M, Sadeghi E, Sadeghi M. Non-hematological adverse events of imatinib in patients with chronic myeloid leukemia in chronic phase (CML-CP). J App Pharm Sci 2015; 5:87—90. doi: 10.7324/JAPS.2015.50213.Petzer AL, Eaves CJ, Lansdorp PM et al. Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia. Blood 1996; 88:2162—2171.Petzer AL, Eaves CJ, Lansdorp PM et al. Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia. Blood 1996; 88:2162—2171.Jabbour E, Deininger M, Hochhaus A. Management of adverse events associated with tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Leukemia 2011; 25:201—210. doi:10.1038/leu.2010.215.Jabbour E, Deininger M, Hochhaus A. Management of adverse events associated with tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Leukemia 2011; 25:201—210. doi:10.1038/leu.2010.215.

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