INCREASE OF DRUG RESISTANCE OF ACUTE MYELOID LEUKEMIA CELLS IN MULTICELLULAR AGGREGATES IN VITRO

Background: Therapeutic efficiency in treatment of acute myeloid leukemia (AML) ranges from 20 to 45%. One of the causes of the latter is a drug resistance acquired by leukemic cells under the influence of treatment with antitumor medicines. More important cause is a development of the primary resistance of myeloid leukemic cells to induction of cellular death associated with elemental microenvironment within the bone marrow. Studying primary resistance is very important, and first of all, to prevent development of drug resistance of leukemic cells and, correspondingly, to increase the efficiency of medicamental therapy. Aim: To study the mechanisms of primary resistance of AML cells to induction of cellular death. Materials and methods: Human AML cells of THP-1 line and mononuclear cells of the bone marrow were used in the study of patients with diagnosed AML. Multicellular aggregates were formed during cell cultivating on the 1.5% agarose. To cut off intercellular adhesion, the cells were cultivated in the medium with methylcellulose (0.9%). The viability of the cells was assessed by reduction of Alamar Blue indicator. Results: Within multicellular aggregates, about 75±5% of THP-1 cells were resistant to the activity of recombinant protein izTRAIL, 70±5% – to etoposide, and 40±7% – to sorafenib. Cutting off intercellular contacts decreased the resistance to them. Within multicellular aggregates of primary mononuclear cells, 45±5% of cells were resistant to sorafenib, 57±4% – to etoposide, and all cells were resistant to izTRAIL. Cutting off intracellular adhesion reduced the resistance to sorafenib and etoposide but not to izTRAIL. Conclusion: In multicellular aggregates, AML cells of THP-1 line and mononuclear cells of the bone marrow showed increased resistance to activity of recombinant protein izTRAIL, etoposide, and sorafenib. Diminishing intracellular adhesion in the medium including methylcellulose decreases cellular resistance to cytotoxic agents

The efficacy of therapy with rituximab (R-CHOP) in patients with diffuse large cells lymphoma

<p>This study aimed to evaluate treatment results in patients with diffuse large cell lymphoma (DBL CL) received R-CHOP program (as 1 st and<br />2 nd line therapy), including cases with complications. We observed 77 DBLCL patients (50 primary and 27 received other chemotherapy programs, in relapse, progression or treatment resistance phase). The median age is 54.1 years (21–79 years). 33 patients (43 %) had a high risk for unfavorable disease course according to IPI. Complications associated with development of severe compression syndromes, which required the appropriate surgical intervention, w as diagnosed in 45 (58.4 %) patients. From 50 primary patients received R-C HOP as the f irst line therapy objective treatment response was registered in 47 (94.0 %). Complete response was registered in 43 (86.0 %). The proportion of patients in whom response was maintained for 6 months w as 72.0 % in group with maintenance therapy and 28.0 % in group without it. These results were achieved when induction period density was 0.9. The last parameter is the ratio of the courses number to their time in mon ths. The density of standard induction R-C HOP-21 is 1.4. From 27 relapse or refractory patients received R-C HOP as the second line therapy objective<br />treatment response was registered in 85.1 % of patients. Induction period density w as 1.03. The proportion of patients in whom response was maintained for 6 months was 74.0 %. Three classes serum Ig concentrations analysis before and after induction period in 16 pati ents showed normal values. With the median (Me) follow-up time in all patients over 24 months 3-years survival w as 93 % and Me w as not achieved. 3-years survival was 100 % in primary patients and 80 % in patients with previously treatment, and Me is also not achieved.</p

Treatment of patients with refractory chronic lymphocytic leukemia with alemtuzumab, alone or in combination with fludarabine

In present study the immediate and long-term therapy results of 14 patients with refractory chronic lymphocytic leukemia (CLL) are analyzed. Treatment program included alemtuzumab alone or in combination with fludarabine

Treatment of patients with refractory chronic lymphocytic leukemia with alemtuzumab, alone or in combination with fludarabine

In present study the immediate and long-term therapy results of 14 patients with refractory chronic lymphocytic leukemia (CLL) are analyzed. Treatment program included alemtuzumab alone or in combination with fludarabine.</p

Treatment efficacy of chronic myeloid leukemia with imatinib in clinical practice

Imatinib (IM) treatment efficacy in 116 chronic myeloid leukemia (CML) patients in different studies was analyzed. Patient group was non‑selective with prospective enrollment. The study was based on real‑time patient’s register allows to treatment quality control due to clinical results. Cytogenetic response (CO), hematological data, and overall survival (OS) were used as criteria for the therapy efficacy. After 12 month of treatment in 46.4 % of CML patients in early chronic phase complete CO (CCO) was obtained, in 33.3 % — in the late chronic phase, and in 13.3 % — in accelerated phase. Deficit of daily imatinib dose and intervals in treatment schedule were made a negative influence on CO quality. The median of OS was 120 months.</p

ASSESSMENT OF THE RESIDUAL TUMOR IN PATIENTS WITH MULTIPLE MYELOMA BASED ON THE ANALYSIS OF THE FREE LIGHT CHAINS OF IMMUNOGLOBULINS IN BLOOD SERUM

Efficiency of the multiple myeloma treatment with chemotherapy including bortezomib was assessed based on determination of the level of immunoglobulin free light chains in blood serum. The method enables estimation of changes in kinetic parameters of the residual tumor, detection of the disease course prognosis, and the choice of the optimal approach to the disease therapy