Background. For many years the primary aim of treatment strategy for ph-negative myeloproliferative neoplasms has been to restrain disease progression, with lasting relief and management of symptoms to improve patients’ quality of life. Generally, this did not lead to a significant increase in life expectancy with primary myelofibrosis and didn’t decrease the risk of fibrosis in patients with polycythemia vera and essential thrombocythemia. To date a new class of targeted drugs has been developed, it is JAK2 inhibitors with pathogenetic effects. The results of clinical trials showed the high efficacy of the first registered drug of this its kind – ruxolitinib – that includes a faster reduction in the symptoms of tumor intoxication and in symptoms associated with the development of splenomegaly and increase in the overall survival rates. It is known that the data obtained during clinical trials of medicines may differ from the results obtained in routine clinical practice. In actual practice drugs are used in a much wider heterogeneous population of patients, less limited first of all by age and comorbid characteristics. It is possible to analyze cohorts of patients including a larger number of clinical cases with a longer follow-up period. In this regard of great interest is the actual clinical experience of long-term use of ruxolitinib in patients whose set is limited only by clinical contraindications for prescribing the drug.Aim. To present our own actual experience of targeted therapy of myelofibrosis and compare the results obtained with the data of clinical trials.Materials and methods. Our analysis includes data from 141 patients (67 (47.5 %) men and 74 (52.5 %) women) in a chronic phase myelofibrosis. All patients received ruxolitinib. Of these, 109 (69 %) patients had primary myelofibrosis, 26 (16 %) – postpolycythemia myelofibrosis, 6 (4 %) – postessential thrombocythemia myelofibrosis. The median age at the start of therapy was 62 (18–84) years. The median disease duration before ruxolitinib was prescribed – 79 (1–401) months. According to the dIpSS (dynamic International prognostic Scoring System) criteria, 13 % of patients were assigned to the low risk group, 38 % – to the intermediate-1, 36 % – to the intermediate-2, 13 % – to the high risk group. Most patients (52 %) had grade 3 bone marrow fibrosis.Results. The median duration of treatment was 18 (range from 1 to 115) months. Symptoms of intoxication were relieved 74 (81 %) of 91 patients, the spleen size decreased in 81 % of patients (the spleen size returned to normal in 25 % of patients). The increase in the median hemoglobin level was 15 %. The proportion of patients requiring blood transfusion decreased by 4 times (from 39 to 9 %). Mean platelet levels normalized in most patients with baseline high and low platelet levels. A complete clinical and hematological response was achieved in 16 % (n = 23) of cases, a partial response – in 26 % (n = 37) of cases, clinical improvement – in 21 % (n = 30), disease stabilization – in 33 % (n = 46) of cases. No response was received in 1 (1 %) patient and in 3 (3 %) cases there was progression of the disease. At the time of analysis, 81 (57 %) of 141 patients were continuing the ruxolitinib treatment. The fatal outcome in 33 (22 %) patients was associated with concomitant diseases, among which 20 (14 %) died from proven COvId-19 infection. Overall survival: 1-year 81 %, 2-year 73 %, 5-year 50 %. Overall survival excluding deaths due to COvId-19: 1-year 92 %, 2-year 85 %, 5-year 70 %. Massive splenomegaly and a high degree of fibrosis were unfavorable predictors of prognosis of overall survival.Conclusion. Target therapy with Janus kinase inhibitor ruxolitinib has demonstrated high efficacy in patients with myelofibrosis in routine clinical practice. The most rapid effect ruxolitinib had on the spleen size and the symptoms of intoxication. Tolerability of ruxolitinib therapy was generally satisfactory. The overall and progression-free survival rates in patients with myelofibrosis, receiving ruxolitinib in the clinical setting was consistent with the results of international multicenter clinical trials.

Aim. To develop a Russian version of MPN10 form for patients with myeloproliferative neoplasms (MPN) compliant with international recommendations. Materials & Methods. The study included 57 patients treated in 2019 at the Hematology Center of Botkin Hospital (n = 30) and the Russian Research Institute of Hematology and Transfusiology (n = 27). Among them there were 36 myelofibrosis, 9 polycythemia vera, and 12 essential thrombocythemia patients. Mean age of the patients was 54.6 years (standard deviation 15.9 years; age range 20-79 years). The male/female ratio was 23/34 (40.4 %/59.6 %). Underlying disease duration was from 1 month to 33 years (mean duration 7 years; standard deviation 8.6 years). Results. A stable structure and a high internal consistency of the form as well as its reproducibility as a tool were demonstrated. The study also confirmed its convergent and discriminant validity and satisfactory sensitivity to changes in a patient's status. Conclusion. The Russian MPN10 version can be used for symptom assessment in MPN patients in clinical practice and scientific research.

Background & Aims. This paper presents the results of the observational study of ibrutinib in patients with chronic lymphocytic leukemia (CLL), conducted in SP Botkin Municipal Clinical Hospital. The main objective was the analysis of complications of ibrutinib and identification of factors, influencing the dosage regimen; the secondary objective was the estimation of the total response to treatment, event-free and overall survival. Materials & Methods. The study included 96 patients with CLL with indications for ibrutinib therapy. The median age was 64,9 years (range 32-91 years), the study population consisted of 69 (72 %) men and 27 (28 %) women. The condition of 25 (26 %) patients according to the ECOG scale was of > 3 points. The disease of stage C were diagnosed in 36 (37 %) patients. Deletion of 17p/TP53 mutations were detected in 29 (33 %) of 87 patients. Seventy patients had refractory CLL. The median of the number of the lines of the previous therapy was 3 (range 1-9). Adverse events were assessed in accordance with the CTCAE criteria, version 4.0; the bleeding severity was evaluated using ITP-specific bleeding score; hematological complications were classified according to the recommendations of IWCLL-2008. Results. Ibrutinib was administered at a dosage of 420 mg per day daily until progression or intolerable toxicity. The median duration of ibrutinib therapy was 10.3 months. brutinib was shown to have moderate toxicity, mostly of grade I or II. The bleeding was the most frequent complication. Of the hematological complications, thrombocytopenia was the most common (35 %); neutropenia < 1 ^x 10⁹/L was observed in 4 patients. GIT complications were identified in 51 (53 %) patients. Atrial fibrillation was registered in 5 patients, who initially had sinus rhythm. The total of 144 infections were diagnosed in 64 (66 %) patients. Severe infections (> grade III) developed in 26 % of patients. The treatment response was assessed in 92 patients. The overall response to treatment was 89 %. Complete remission, partial remission and partial remission with lymphocytosis were achieved in 4 (4 %), 57 (62 %), and 21 (23 %) patients, respectively. The event-free survival and overall survival by the month 10 was 90 % and 91 %, respectively. For this observation period, ECOG status and the number of the lines of therapy prior to ibrutinib had the prognostic value. Conclusion. Ibrutinib was shown to have high efficiency in relapsed/refractory forms of CLL. The nature of the ibrutinib toxicity is fundamentally different from that of the conventional chemotherapy. The frequency of ibrutinib therapy complications and patients' non-compliance depends on the intensity of the previous treatment of CLL. Despite a short observation period, it can be concluded that ibrutinib had the greatest impact on the patient's quality of life when administered for the first relapse. The low toxicity of ibrutinib is likely to allow the combination with other antitumor agents.

Цель. Оценить собственный опыт использования бозутиниба у больных хроническим миелолейкозом (ХМЛ) при непереносимости и резистентности к другим ингибиторам тирозинкиназ (ИТК), а также сравнить полученные результаты с данными клинических исследований. Материалы и методы. Для анализа использовались амбулаторные карты 51 больного (25 мужчин и 26 женщин; возраст 28-86 лет, медиана 56 лет) с диагнозом ХМЛ. Фаза заболевания к началу терапии бозутинибом: хроническая-у 37 пациентов, акселерации-у 8, бластный криз-у 6. Бозутиниб назначался в следующих линиях терапии ИТК: вторая-у 10 пациентов, третья-у 18, четвертая-у 23. Причины перехода на бозутиниб: непереносимость предыдущего ИТК-у 21 пациента, резистентность к предыдущему ИТК-у 30. Результаты. Медиана продолжительности терапии бозутинибом составила 6 мес. (диапазон 1-50 мес.). Профиль токсичности и переносимость бозутиниба в обычной клинической практике соответствовали данным клинических исследований. Лечение было прекращено по причине нежелательных явлений только у 5 (10 %) больных. Частота ответов во всей группе больных составила: полный гематологический-88 %, при этом у

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