Relapsed and refractory (R/R) multiple myeloma (MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short. In patients with R/R MM after therapy of bortezomib and/or immunomodulators a bendamustine-based treatment can be used as “salvage”.

In this retrospective analysis we have identified 32 patients with R/R MM by means of case research, have been bendamustine-based treated at Hematological Clinics of Russian Federation since 2011. Median age was 67 (43–81) years, the female/male ratio was 2.5:1. After in median 2 (1–7) lines of prior therapy patients received in median 3 (1–9) cycles of bendamustine-based therapy. Bendamustine dosage was 70–120 mg/m2 /day on 2 days of each 28-day cycle until progressive disease or intolerability. Overall rate response was 56.2 %: 21.9 % partial response, stable disease 34.4 %. Median time to progression was 5.3 (0.8–18.0) months and median overall survival was 25.4 (0.8–47.1) months. Hematologic toxicity was in 53.2 % of patients.

The article is focused on the results of the multicenter observational study “Quality of life and symptom profile in patients with chronic myeloid leukemia in chronic phase in long-term follow-up of second-line treatment” (2012–2015). Thirty imatinib-resistant or-intolerant patients with chronic myeloid leukemia in chronic phase were observed in the real-world clinical setting during 24 months after start of second-line treatment with dasatinib. Mean age – 48 years old (SD = 13.1); males / females – 14 / 16; one third of patients were with comorbidity, Charlson Index – 0–5 scores. All the patients received dasatinib in the dosage of 100 mg daily. Study time points – 12, 18 and 24 months after second-line treatment start. Treatment outcomes were analyzed in terms of clinical efficacy and safety as well as in terms of patient-reported outcomes, including quality of life and symptom profile assessment. For quality of life and symptom assessment the SF-36 and CSP-CML questionnaires were used, respectively. Statisticallly significant changes in quality of life and symptom severity were analyzed by generalized estimated equation (GEE). Complete hematological response was observed in 96.3 % patients, complete cytogenetic response – in 66.6 % patients, complete or major molecular response – in 60 % patients. The acceptable tolerability of dasatinib treatment was shown during long-term follow-up: hematological and non-hematological serious adverse events were rare and didn’t lead to treatment discontinuation. Significant improvement of physical functioning, role physical functioning, role emotional functioning, vitality and mental health as compared to base-line parameters was observed (p < 0.05). The severity of a number pronounced symptoms decreased and the proportion of patients with severe symptoms reduced (p = 0.01) after 24 months of second-line treatment start. Quality of life treatment response in terms of stabilization or improvement was registered in 83 % of patients. The data of this real-world study in CML patients are in line with the results of clinical studies in terms of dasatinib treatment efficacy and safety. In addition, they demonstrate the value of patient-reported outcomes to evaluate benefits and risks of long-term dasatinib treatment from patient perspective.

The literature review and own long-term polycythemia vera diagnosis and treatment experience are presented in this article. The results of newest advances in pathogenesis description, modern diagnostic techniques and treatment modalities in polycythemia vera are included. The JAK-STAT signal pathway activation now recognized as main pathogenesis mechanism of polycythemia vera. In this case this activation caused almost exlusively by JAK2 gene mutations. Authors demonstrate their own data about epidemiology, clinical signs and diagnostic and treatment results of 252 polycythemia vera patients. The most frequent clinical symptoms at diagnosis were: plethora, headache and dizziness, fatigue, pruritus. Diagnostic criteria and thrombotic complications prognostic scale are presented. The thrombosis frequency in this polycythemia vera patients group was 11.1 %. It was included 3.6 % of myocardial infarctions and 5.2 % of strokes. The thrombotic complications rates statistically differed in various prognostic groups. For example, from 2.6 % in low-risk group to 20.6 % in high-risk thrombosis group. The used personalized polycythemia vera management algorithm is listed. The treatment methods features, target drugs (Janus kinases inhibitors) trials results are discussed.

Relapsed and refractory multiple myeloma (MM) is defined as progression during anticancer therapy, or within 60 days of therapy completion. Patients with double resistance to bortezomib and lenalidomide that is two key anti-myeloma drugs are considered to have a very poor prognosis, and new regimens are needed to improve this setting. Pomalidomide is an immunomodulatory drug third generation, studied in combination with low-dose dexamethasone (LDD) as salvage therapy for patients with double refractory. This article reviews the clinical pharmacology, therapeutic efficacy and safety, dosage and administration, peculiar properties of the practical application of pomalidomide. The article is illustrated by the description of a 59-year-old woman with relapsed and refractory MM, who received pomalidomide in combination with LDD. Medical history prior to treatment with pomalidomide was included 8 lines of therapy conducted over 6.5 years, with the formation of the double refractory to lenalidomide and bortezomib. In March 2012, treatment with pomalidomide (4 mg days 1–21 of a 28-day cycle) and LDD (160 mg / cycle) has been started as the ninth line. In total, up to March 2014 the patient received 30 cycles of therapy with pomalidomide. After the first 2 cycles documented partial response (52 % reduction of IgGk), the deepest response is received after 10 cycles (82 % reduction). The patient is alive at the time of this article. The duration of response to pomalidomide is 25 months and overall survival from the time of his appointment is more than 37 months. In addition, this review presents the results of base clinical trials testing pomalidomide and LDD. Problems of development of new treatment regimens based on pomalidomide for relapsed and refractory MM are also discussed.

We analyzed susceptibility to anidulafungin of yeasts clinical strains of Candida (14 species), Cryptococcus (1 species), Geotrichum (1 species), Rhodotorula (1 species) and Saccharomyces (1 species). We revealed high anidulafungin activity against Candida spp., both common species and rare pathogens of candidiasis. It was found that over 99 % of Candida strains do not have an acquired resistance mechanisms to anidulafungin (microbiological criteria). The anidulafungin is not active against strains of Cryptococcus neoformans and Rhodotorula mucilaginosa.

During therapy with second generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia, a number of patients demonstrate non-hematological toxicity of various degrees. The article contains review of references about second generation tyrosine kinase inhibitors effect on the frequency of cardiovascular and metabolic problems.

The molecular basis of the D-negative phenotype formation in humans is presented in this article. Causes of true and false D-negative phenotype appearance are described. The basis of true D-negative phenotype are changes in the genome, that lead to complete lack of RhD antigen expression on the red blood cells surface, or defective expression of RhD antigen, not detectable by serological methods. The reason for the false D-negative phenotype is the insufficient sensitivity of routine serological methods. Cases of true and false D-negative phenotype identified during the examination of the Russia residents are described. We were able to identify one case of true (RHDψ) and five cases of false D-negative phenotype (RHD weak type 2 – two cases, RHD weak type 15 – one case and RHD weak type 20 – two cases) by molecular method.

Serological methods of Rhesus antigens identification in humans cannot identify D-antigen variants. In this article the serological characteristics of Rhesus antigen D weak type 4.2. (Category DAR) are described.

Thrombosis is a fatal hemostatic disorders occurring in various conditions ranging from pregnancy and surgery to cancer, sepsis and heart attack. Despite the availability of different anticoagulants and accumulated clinical experience, proving their effectiveness, thrombosis remains a major cause of morbidity and mortality. This is largely due to the fact that conventional laboratory coagulation tests are not sufficiently sensitive to the hypercoagulable state, and they are difficult to use for assessing the risk of thrombosis. Specific molecular markers (D-dimers, fibrinopeptide, thrombin-antithrombin complex) are more effective, but also have a large number of disadvantages. A possible solution is the use of integrated test, which simulate in vitro the majority of the physiological coagulation processes. In the first part of this paper the biochemical processes that cause the risk of thrombosis were discussed.

In the second part we present a review of the existing data about ability of integrated tests, as already introduced in clinical practice, and the new (test of thrombin generation, thromboelastography, thrombodynamics, perfusion chamber) to assess the risk of thrombosis in different pathologies. We can conclude that the existing integrated tests can be an important tool in the diagnosis of hypercoagulation. However, lack of standardization prevents their use: various tests and modifications of each test are different in sensitivity and specificity for each pathological condition. Furthermore, even in situations where the tests can reliably identify a group of patients with different degrees of thrombosis risk, their use in clinical practice is often difficult, since the differences between these groups were statistically significant, but the normal range and patients significantly overlap.

Новый препарат компании «Рош» Газива® (обину- тузумаб) для терапии пациентов с хроническим лим- фоцитарным лейкозом (ХЛЛ), которые не лечились ранее, станет доступен на российском рынке с сентя- бря 2015 г