A lower chemotherapeutic load and a small number of allogeneic BMTs did not affect total positive treatment results in adult patients with ALL, by complying with the principle achieving the continuity of cytostatic effects and by preserving the total cytostatic loading dose. The results of the Russian investigation casts some doubt on the necessity of using very intensive consolidation cycles and performing a large number of allogeneic BMTs in adult patients with ALL.

The reaction of 2-allylthiobenzimidazole (I) with bromine in acetic acid gives the hydrobromide salt of 2-(2,3-dibromopropylthio)benzimidazole, which is cyclized by the action of bases to give 3-bromo-3,4-dihydro-2Hbenzimidazolo[2,1-b][1.3]thiazine [1,2]. In the present work, we studied the reaction of aUyl sulfide I, 2-allylthio-l-allylbenzimidazole (II), 2-allylthio-l-methylbenzimidazole Off), and 2-styrylthiobenzimidazole (IV) with iodine in various solvents.Sulfide I was obtained by the allylation of 2-benzimidazolethione (V) using an equimolar amount of aUyl bromide in alcohols, DMF, and water. A mixture of sulfides I and II is formed in the case of excess allyl halide.Sulfides II and HI were obtained by the alkylation of sulfide I using allyl bromide, methyl iodide, or dimethyl sulfate in ethanol in the presence of KOH or sodium ethylate as well as in a two-phase system 1-120 + KOH + CCI 4 in the presence of tetrabutylammonium bromide.

The ALL-2009 protocol allows both the federal and regional centers to obtain the long-term results comparable with those of current foreign studies: OS (54.2%), RFS (56.5%); and relapse risk (35.4%). Multivariate analysis has identified age (over 30 years), initial leukocytosis (30·109/l and more) and t(4;11) among the main clinical prognostic factors. Gene mutation detection evaluated in a small number of patients (8/36) is not a poor prognostic sign. There is a need for further investigations with centralized evaluation of the mutation status of leukemic cells and the clearance of minimal residual disease.

Introduction Intensive “pediatric oriented” treatment with heavy cytostatic load, incorporation of allogeneic HSCT is now considered a backbone approach in adult ALL therapy. Highly myelosuppressive treatment is more toxic and less reproducible, so RALL has initiated non-intensive but non- interruptive protocol “ALL-2009”and started a prospective multicenter trial for adult Ph-negative ALL based on: 1) the replacement of prednisolone (Pdn) 60 mg/m2 with dexamethazone (Dexa) 10 mg/m2 if blast cells are >25% in bone marrow after 7 days of prephase; 2) de-intensified but non-interruptive treatment with doses modification according to the myelosuppression with total treatment duration of 127 weeks; 3) prolonged implication of L-asparaginase (total proposed dose 590.000 IU/m2); 4) autologous hematopoietic stem cell transplantation (HSCT) after non-myeloablative BEAM conditioning followed by prolonged maintenance – for T-cell ALL patients. Allo-BMT was an option for high risk patients with sibling donors. The study is registered on the ClinicalTrials.gov public site; NCT01193933. Methods and patients From Jan 2009, till June 2014, 30 centers enrolled 250 pts: median age 30 years (15-60 years), 115f/135 m; in 2,4% phenotype was unknown (n=6), B-lineage ALL - 63,2% (n=158), T-lineage ALL - 34% (n=85), biphenotypic - 0,4% (n=1). Cytogenetics was available in 62,4% of patients (n=156) and 41% of them (n=64) had normal karyotype (NK). 25,2% of patients (n=63) were in the standard risk (SR) group (WBC <30 for B-lineage, <100 for T-lineage; EGIL BII-III, T-III; LDH < 2N; no late CR; t(4;11)-negative), 59,2% (n=148) - in the high risk (HR) group (WBC >30 for B-lineage, >100 for T-lineage; EGIL BI, T-I-II-IV; LDH > 2N; late CR; t(4;11)-positive), 39 patients were not qualified by risk group. The analysis was performed in June 2014. The median time of follow-up was 26,1 mo. Results Prednisolone was replaced with dexamethazone after prephase in 68,1% of patients (135 of 198). The portion of non-responders to PRD in SR and HR groups was 54% and 67%, respectively (p=0,06). CR rate in 228 available for analysis patients was 87% (n=198), induction death occurred in 10,5% (n=24), resistance was registered in 2,5% (n=6). The majority of CR patients (91%) achieved it after prephase (7,1%, n=16) and the 1st phase of induction (83,9%, n=164). Late responders constituted 9% (n=18). None of those factors (PRD sensitivity, initial risk group, immunophenotype, late response) influenced overall (OS) or disease-free survival (DFS). OS rate in older ALL patients (>30) was substantially less than in younger ones (52,7% vs 73,6%, p=0,0009). DFS was comparable - 61,2% vs 71,5%, p=0,1. 24 of 75 (32%) CR T-ALL patients underwent autologous BMT after BEAM conditioning at a median time of 6 mo from CR and proceeded to further maintenance. No relapses were registered in this group so far. Allogeneic BMT was performed only in 14 patients (Ò-ALL-7, B-ALL-7) on the protocol. Totally 47 patients (20,6%) relapsed (16 with T-lineage, 31 with B-lineage ALL). At 48 mo OS for the whole group constituted - 65,6%, DFS - 69,3%. OS and DFS differed in B-ALL patients with NK in comparison with abnormal karyotype: 80% vs 57%,(p=0,01) and 81% vs 61%, respectively (p=0,02), but not in T-ALL patients. Conclusions Our data demonstrate that the proposed treatment approach is rather effective and reproducible. OS and DFS did not depend on various common risk factors (initial risk group, WBC, LDH, immunophenotype, late response, PRD resistance). The only independent risk factor for OS was age (>30 y). In B-cell ALL abnormal karyotype became an independent adverse risk factor for OS, DFS, relapse incidence. Fig.1 Overall survival (A) according to age in the whole cohort and disease-free survival (B) in B-cell ALL according to karyotype Table 1 (A) OS in different age groups (B) DFS in B-cell ALL Figure Figure. (A) OS in different age groups Figure Figure. (B) DFS in B-cell ALL Disclosures No relevant conflicts of interest to declare.

Получено 28 июня 2009 г.Найдено точное решение стационарной задачи ветрового движения вязкой двухслойной жидкости для двумерного в вертикальной плоскости течения и для дрейфовой составляющей трехмерного течения. На дне бассейна ставится условие проскальзывания, на вертикальных боковых стенкахусловие непротекания. Приводятся примеры расчетов конкретных течений и сравнение полученных результатов с решениями аналогичной задачи по модели Экмана (без учета горизонтальной вязкости).Ключевые слова: вязкая жидкость, ветровое движение жидкости, модель Экмана Abstract. -Exact solution of the stationary problem of wind-induced flow of two-layered viscous fluid is found for two-dimensional in vertical plane current and for drift current in three-dimensional case. The condition of sliding is set on the bottom of a water body. The condition of nonpassage is set on the lateral surface. Results of some calculations are given in comparison with those obtained using Ekman's model (which does not take into account horizontal viscosity of the layer). ВведениеПроблема определения ветрового движения жидкости в замкнутом водоеме очень сложная, но практически важная задача [5]. В общей постановке она сводится к решению нестационарной начально-краевой задачи для системы нелинейных уравнений, решение которой возможно только численными методами.Большую помощь при этом оказывают аналитические решения упрощенных задач, получающихся в результате правдоподобных предположений. При этом выстраивается некоторая иерархия используемых моделей: достаточно простые модели двумерного (в вертикальной плоскости) стационарного течения однородной жидкости без учета горизонтальной вязкости, модели с учетом горизонтальной вязкости, трехмерные течения без учета членов горизонтальной вязкости, с учетом этих членов, нестационарные течения [1][2][3][4]. Чем проще модель, тем больше аналитических решений удается получить и проанализировать. Так, для первой из указанных моделей известно аналитическое решение для случая неровного дна и переменного коэффициента вертикального турбулентного обмена. Чем сложнее модель, тем аналитических результатов, как правило, меньше, и задача решается численными методами.