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11 ФГБУ «Российский научно-исследовательский институт гема-тологии и трансфузиологии» ФМБА РФ, ул. 2-я Советская, д. 16, Санкт-Петербург, Российская Федерация, 191024 2 ГБУЗ «Городская больница № 15», ул. Авангардная, д. 4, Санкт-Петербург, Российская Федерация,198205 3 Александровская городская больница № 17, пр-т Солидарности, д. 4, Санкт-Петербург, Российская Федерация, 193312 РЕФЕРАТ Цель. Поиск вариантов ответа на лечение азацитидином, связанных с улучшением показателей общей выживае-мости (ОВ) больных с острыми миелоидными лейкозами (ОМЛ) и миелодиспластическими синдромами (МДС). Методы. Проведен ретроспективный анализ историй бо-лезни 14 больных ОМЛ и 13 больных МДС в возрасте 39-84 года, которым назначался азацитидин по 75 мг/м 2 под-кожно в течение 7 последовательных дней каждые 28 дней. Эффективность оценивали по модифицированным крите-риям IWG 2006 г. ОВ рассчитывали от даты начала терапии азацитидином. Результаты. Число проведенных курсов было 2-25. Пол-ная ремиссия (ПР) достигнута у 6 (22,2 %) больных, вклю-чая 4 ОМЛ и 2 МДС. Костномозговая полная ремиссия (кмПР) констатирована у 1 (3,7 %) пациента с МДС. Ге-матологическое улучшение зафиксировано у 11 (40,7 %) больных, из которых 5 были с ОМЛ и 6 -с МДС. Общий ответ составил 66,7 % (18 из 27 больных). Не обнаруже-но связи эффективности терапии с возрастом, вариантом заболевания, длительностью предшествующего периода, исходными уровнями гемоглобина, лейкоцитов и тромбо-цитов, зависимостью от трансфузий эритроцитной взвеси и тромбоконцентрата. Терапия расценена как неэффек-тивная у 9 (33,3 %) больных. У 4 пациентов с ОМЛ и 3 -с МДС констатирована стабилизация с сохранением потреб-ности в трансфузии компонентов крови. У 2 больных от-мечено постепенное повышение числа бластных клеток в костном мозге. При сроке наблюдения 2-29 мес. медиана ОВ всех больных составила 11,5 мес. Медиана ОВ в группе ABSTRACTAim. To evaluate types of response to azacitidine associated with improvement of overall survival (OS) rates of patients with acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS). Methods. A retrospective analyses of medical records of 14 AML patients and 13 MDS patients at the age of 39 to 84 treated with azacitidine at a dose of 75 mg/m 2 subcutaneously for 7 subsequent days every 28 days was performed. The therapy effectiveness was evaluated according to modified 2006 IWG criteria. The OS was calculated beginning with the date of initiation of the azacitidine therapy. Results. From 2 to 25 azacitidine cycles was performed. Complete remission (CR) was achieved in 6 patients (22.2 %) including 4 AML and 2 MDS patients. Bone marrow remission (mCR) was diagnosed in 1 MDS patient (3.7 %). Hematological improvement was obtained in 11 patients (40.7 %) including 5 AML and 6 MDS patients. The overall response was 66.7 % (18 to 27 patients). There was no correlation between the therapy effectiveness and patients' age, disease type, duration of the previous period, baseline hemoglobin, leukocytes, and platelets levels, and dependence on tra...

Background. Thrombotic complications are one of the main problems of polycythemia vera (PV) treatment. They significantly impair the quality of life of these patients and may lead to the lethal outcome. A thrombotic event often precedes the diagnosis of this hematological disease. The pathogenesis of thrombosis in myeloproliferative neoplasms, PV, in particular, is a complex one. Prescription of antiaggregants in the absence of thrombosis and anticoagulants after a thrombotic event requires special attention and development of corresponding recommendations. The prescription of anticoagulants is impossible without taking into account the risks of hemorrhagic complications, which are also typical for myeloproliferative neoplasms. Aim. Assessment of the impact of hereditary thrombophilia genetic markers on the risk of thrombotic complications in patients with PV. Methods. The study examined 116 patients with PV, who were screened for markers of hereditary thrombophilia: factor V (G1691A, FV Leiden), prothrombin, methylene-tetrahydrofolate reductase (MTHFR), fibrinogen (F/), plasminogen activator inhibitor (PA/-1), and platelet fibrinogen receptor type ///A (GP///A). The incidence of these markers and their role in thrombosis in such patients was investigated. Results. The study provided data on the incidence of hereditary thrombophilia markers in patients with PV. Statistically significant differences in the incidence of these markers and homocysteine level were found between patients with thrombosis and without them. Conclusion. The information about the hereditary thrombophilia markers presence may be useful for the prescription of adequate antiaggregant and anticoagulant therapy for PV patients. Further research in this field is justified and it will probably demonstrate the relevance of hereditary thrombophilia markers as prognostic factors for thrombotic complications risk assessment.

Background & Aims. The presence of different molecular genetic markers of clonality (mutations in JAK2, MPL, CALR) or their absence (triple negative status, TN) in essential thrombocythemia (ET) indicates a biological heterogeneity of the disease and can determine its clinical forms. The aim was to evaluate the association of molecular genetic markers with the clinical form and the prognosis of ET. Materials & Methods. We analyzed the data of 240 patients with ET at the age of 20-91 years (median age 58.7 years), who were observed in the Russian Research Institute of Hematology and Transfusiology from 1999 to 2016 (median observation period 37.2 months). Results. The JAK2V617F (JAK2+) mutation was found in 182 (75.9 %) of 240 patients. CALR (CALR+) mutations were found in 30 (12.5 %): type 1 (CALP7+) mutations in 13/30 (43.3 %) and type 2 (CALR2+) in 17/30 (56.7 %). MPL (MPL+) mutations were found in only 2 (0.8 %) of 240 patients. None of the mutations were detected in 26 (10.8 %) of 240 patients (TN status). Significantly higher platelet counts were observed in CALP7+ and CALR2+ subgroups during the primary diagnosis of ET compared with JAK2+ and TN groups. The mean platelet counts were 1252 * 10⁹/L for CALR2+ and 1079 * 10⁹/L for CALP7+ vs 841 * 10⁹/L (p < 0.001; p = 0.06) and 775 * 10⁹/L (p < 0.001; p = 0.04) for JAK2+ and TN, respectively. Thrombosis was diagnosed in 50 (27.4 %) of 182 patients of the JAK2+ subgroup, in 8 (30.7 %) of the 26 patients of the TN subgroup, and in 2 (18.2 %) of 11 patients of the CALP7+ subgroup. No thrombosis was found in the CALR2+ and MPL+ subgroups (p < 0.001). In general, the CALP7+ status was characterized as the most favorable in terms of prognosis (5-year overall survival rate of 100 %), compared to the least favorable TN status (5-year overall survival rate of 85 %). Conclusion. Mutations in the CALR gene were characterized by a more favorable prognosis in comparison with JAK2+and TN, as well as a decrease in the risk and frequency of thrombosis, despite higher platelet counts. TN-status of ET was associated with unfavorable prognosis.

Background: Studies over the past decade, have greatly improved our understanding of the molecular basis of multiple myeloma and mechanisms of disease progression. Metaphase cytogenetics and fluorescence in situ hybridization (FISH) help us to identify the most frequent genetic abnormalities. The division of patients into various risk groups based on the chromosomal markers is being utilized by many centers for select and optimize of therapeutic strategy. However, such molecular risk-stratification systems are repeatedly updated in accordance with the emergence of new information about the prognostic impact of anomalies. The role of complex karyotype and combination of genetic abnormalities remains unclear. Aims: To estimate the incidence of genetic abnormalities and their impact on overall and progression-free survival in patients with newly diagnosed multiple myeloma (NDMM). Methods: The study included 159 patients (median age 63 years, range 28 -83; male: female ratio -1:1.37) with NDMM. Metaphase cytogenetics on bone marrow samples was done by standard GTG-method. FISH analyses were performed according to the manufacturer's protocol for detection primary IgH translocations, 13q (13q14/13q34) deletion, 1p32/1q21 amplification/deletion, P53/cen 17 deletion (MetaSystems DNA probes). We additional searched the t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20) in patients with IgH translocation. All patient was treated by bortezomib-based programs (VD, CVD, VMP, PAD). Results: The frequency of genetic abnormalities in NDMM patients was 49% (78/159). IgH translocation was detected in 26.4% (42/159) patients: t(11;14) -16.3% (26/159), t(4;14) -5.0% (8/159); TP53/del17p -5.6% (9/159); 1p32/1q21 amp/del -12% (19/159); hypodiploidy -3.1% (5/159); hyperdiploidy -1.25% (2/159); del5q -0,6% (1/159); other -not found. Combination two aberrations was discovered in 11.9% (19/159) patients, complex abnormalities (≥3 aberrations) -in 4.4% (7/159) patients. The median OS in "two aberration'' and "complex abnormalities'' groups were lower than in standard-risk mSMART 3.0 (normal, t(11;14), hypodiploidy, hyperdiploidy and other): 49 months, 37 months and not reached, respectively (p = .02). The median PFS for these groups was 12 months, 11 months and 30 months, respectively (p = 0.004). We modified high-risk mSMART 3.0 by adding "two aberration'' and "complex abnormalities'' groups on based the OS and PFS results. The median OS in standard-risk mSMART 3.0 was not reached, in high-risk mSMART 3.0 mod -50 months; 5-years OS was 65% and 38%, respectively (p = 0.01). The median PFS was 58 and 29 months, respectively (p = .02). Summary/Conclusion: Combination two aberrations and complex abnormalities are unfavorable prognostic markers. The median OS and PFS was higher in standard-risk than high-risk patients mSMART 3.0 mod . It can be useful for update risk stratification in future.