Introduction. JAK2V617F mutation is detected in approximately 50 % of patients with essential thrombocytosis (ET) and primary myelofibrosis (PMF). In 2013 most of the JAK2 negative patients showed mutations in the CALR gene. Diagnostic value of JAK2 and CALR mutations is high, but their prognostic significance is not sufficiently clear. Data on impact of JAK2 and CALR mutational status on thrombotic complications in ET and myelofibrosis patients are contradictory.

The aim of the study was to identify clinical and laboratory features in patients with ET and PMF in accordance with the mutational status of JAK2V617F and CALR gene.

Materials and methods. Patients treated in Almazov National Medical Research Center (St. Petersburg), Chuvash Republican Clinical Hospital (Cheboksary), Irkutsk Regional Clinical Hospital (Irkutsk),  Kirov Research Institute of Hematology and Blood Transfusion (Kirov) was included in the retrospective study. CALR mutation (1 and 2 types), MPL W515L/K and JAK2V617F mutation were detected in peripheral blood cells.

Results. We identified that 21 % (n = 16) of ET patients had thrombotic complications, and they occurred more often among JAK2V617F positive patients (p <0.05). The median of hemoglobin level in PMF was the lowest in the group of triple negative patients. The level of leukocytes in PMF was higher in the group of triple negative patients than in the group with mutated CALR (p = 0.014).

Conclusion. JAK2V617F mutation in ET patients was associated with a high risk of thrombosis. Patients with CALR mutations may have a favorable prognosis regarding to thrombotic complications. Some laboratory features of CALR mutations in ET and PMF patients have been revealed.

Introduction. CDKN2A deletion is a frequent cytogenetic abnormality in acute lymphoblastic leukemia (ALL),  ranging from 18 to 46 %, associating with Т-cell ALL, high WBC counts, splenomegaly, lymphadenopathy. In pediatric group of patient’s CDKN2A deletion was associated with poor event-free survival. The prognostic impact of CDKN2A deletion in adult ALL patients appear controversial.

The aim of this study was to evaluate the prognostic impact of the CDKN2A deletion in adult patients with acute lymphoblastic leukemia, which were treated by RALL-2009.

Materials and methods. We present the results of the CDKN2A deletion in 110 adult patients with newly diagnosed Ph-negative (Ph‒) ALL, which were treated by RALL-2009  (NCT01193933)  since June 2009 till September 2016. Patients characteristics: the median age was 26 years (range 15–54), 65 (59 %) of the 110 patients had a B-precursor phenotype, 42 (38 %) had a T-cell phenotype, 3 (2.7 %) patients – biphenotypical ALL. Interphase fluorescence in situ hybridization (FISH)  was performed for detection CDKN2A deletion, MLL, с-MYC rearrangement, TP53 deletion, t (1;19) (q23; p13.3)/TCF3-PBX1, t (12;21) (p13.2; q22.1)/ETV6-RUNX1 and iAMP21. The median follow-up was 31 months (0.5 to 80 months).

Results. The prevalence of the CDKN2A deletion in all studied population was 24.3 % (27 cases). Our study demonstrated that CDKN2A deletion had no significant association with age, sex and blast cells immunophenotype. The analysis for T-ALL has detected that CDKN2A deletion was strongly associated with high WBC count (the median is 86 × 109/L;  p = 0.006) and with high lactate dehydrogenase level (the median is 3062 IU; p = 0.0004). But in BCP-ALL cases similar correlation was not found. CDKN2A deletion didn’t have statistically significant impact on outcome of patients. OS for patients with BCP-ALL with and without deletion was 85 and 76 % (p = 0.35); DFS was 92 and 65 % (p = 0.07), respectively. OS for T-ALL patients with and without deletion was 90 and 80 % (p = 0.63); DFS was 100 and 82 % (p = 0.24), respectively.

Conclusion: CDKN2A deletion is not adverse prognostic factor in adult ALL patients treated according to protocol RALL-2009.

Introduction. The anthracycline antibiotics cause clinically significant manifestations of cardiotoxicity (СТ) – myocardial injuries, reducing both quality and life expectancy of the oncological patients.

The purpose of the study was to evaluate the incidence and risk factors anthracycline-induced СТ in patients with hemoblastosis.

Materials and methods. The study included 131 case histories of patients with hemoblastosis, treated with anthracyclines. Patients were divided into two groups according to age – the 1st group involved 77 patients aged from 18 up to 50 years (average age of 25.6 ± 3.4 years), the 2nd – 54 patients aged from 51 up to 75 years (average age of 56.8 ± 4.6 years). At the first investigation phase we studied the incidence of anthracycline-induced СТ in various age groups patients. The second phase devoted to studying potential risk factors (a cumulative dose more than 240 mg/m², a female, an age, the accompanying application of mediastinal radiation therapy or other cardiotoxic drugs, cardioprotection absence) influence on anthracycline-induced CD frequency.

Results. The incidence of CT in young patients was 38.2% (95% confidence interval (CI) 25.6–51.6%), among the older age group – 14.3% (95% CI 5.3–26.7%). The incidence of CT is significantly higher among young people (χ²  = 5.63, p = 0.018). According to the results of univariate regression analysis, significant risk factors for the development of myocardial damage in patients with CT signs were: age <50 years – the odds ratio (OR) 2.69; 95% CI 1.05–6.84; the cumulative anthracycline dose more than 240 mg/m²  by doxorubicin (OR 5.17, 95% CI 1.38–27.55)  and the absence of prophylactic cardioprotective therapy (OR 23.38, 95% CI 6.49–84.14 ). In multivariate regression analysis independent risk factors for myocardial damage development were only the cumulative anthracyclines dose more than 240 mg/m²  (OR 6.17, 95% CI 1.32–28.71)  and the absence of prophylactic cardioprotective therapy (OR 2.82, 95% CI 1.09–7.28).

Conclusions. Statistically significant higher anthracycline-induced cardiotoxicity frequency appeared in young patients. Reliable (р <0.05) cardiotoxicity risk factors were cumulative dose more than 240 mg/m²  and cardioprotection absence.

The aim of this study was to evaluate incidence and type of infections in patients with acute lymphoblastic leukemia (ALL) treated with ALL-2009 protocol during different chemotherapy cycles.

Materials and methods. Prospective study (2013–2015) included patients with de novo ALL, receiving chemotherapy with ALL-2009 protocol. Patients were followed for 6 month. Total of 44 patients with ALL aged 17–61 years (median age 26 years) were enrolled in the study. These patients received 272 chemotherapy cycles (51 – induction, 221 – consolidation). On admission to  National Research Center for Hematology hyperleukocytosis was in 25 % of patients, ECOG score ≥ 3 – in 61 %, severe infections – in 22 %, hospitalization to intensive care unit (ICU) – in 9 %.

Results. Neutropenia was in 91 (38 %) of 272 chemotherapy cycles, predominantly in induction (71 %) compared to consolidation (25 %), odds ratio (OR) 7.2; p <0.0001. Median duration of neutropenia was more prolonged in induction compared to consolidation (24 vs 7 days; p <0.0001). Patients were transferred to ICU in 4 % of chemotherapy cycles, predominantly in induction (18 %) then in consolidation (0.5 %; OR 47.1; p <0.0001).

Mean number of infections was 1.1 (0–3) per patient and 14 (32 %) of 44 patients did not receive any antibiotics throughout all study period (6 month). Febrile neutropenia occurred in 18 % of chemotherapy cycles, and more frequently in induction compared to consolidation (55 % vs 10 %, OR 5.9, p <0.0001). The majority of febrile events were attributable to clinically documented infections (47 %), followed by fever of unknown origin (29 %) and bloodstream infection (BSI) (24 %). Clinically documented infections were represented by pneumonia (35 %) and cellulitis (12 %). Gram-negative and Gram-positive bacteria accounted for 67 % and 33 % of BSI pathogens (n = 15), consequently. Invasive mycoses (IM) were in 14 % of patients. The main IM was invasive aspergillosis (9 %). All cases of invasive aspergillosis occurred in induction. None cases of IM caused by molds were observed in consolidation.

Conclusions. Our study demonstrates relatively low incidence of infections on different chemotherapy cycles in ALL patients treated with ALL-2009 chemotherapy protocol and 32 % of patients did not receive any antibiotics throughout all study period (6 month). Bacterial and fungal infections prevailed in induction compared to consolidation. The predominant IM was invasive aspergillosis. All cases of IM caused by molds occurred in induction.

A wide range of toxic complications of BCR-ABL tyrosine kinase inhibitors therapy due to non-targeted inhibition of other protein kinases. This is of particular importance in the treatment of patients with Ph-positive lymphoblastic leukemia, who receive, in addition to tyrosine kinase inhibitors, cytotoxic drugs, enhancing myelotoxicity and, as a consequence, infections and thrombo-hemorrhagic complications. In addition, complex inter-drug interactions lead to the manifestations of combined toxicity. This article presents a case report of patient with relapsed acute Ph-positive lymphoblastic leukemia, treatment of which was accompanied by numerous complications, especially during treatment of II and III generation tyrosine kinases inhibitors.

The aim of this study was to analyze the basic epidemiological parameters of MM in the Kirov region based on own regional population register data.

Materials and methods. Five hundred and sixty-seven patients with newly diagnosed MM between 1994 and 2016 were included. The median age was 64 years (range, 29–90).  The age-standardized incidence of MM in Kirov region was 1.8 cases per 100.000/year.

Results. During research period (23 years) we have the positive trend of the incidence and prevalence of MM and negative tendency of mortality every year. Our prognosis of the intensive incidence in Kirov region is 2.2–2.3  cases per 100.000 in 2017–2019  years. The 5-year overall survival rate (5y-OS) was 18 % (1994–1999);  24 % (2000–2005) and 36 % (2006–2011) respectively. The median OS was 28; 26 and 38 month respectively. The median OS for patients who diagnosed in the period 2012–2016  was not achieved. The reason for the increase in the prevalence of the disease and the reduction in mortality is the greater effectiveness of new bortezomib-containing chemotherapy regimens.

Conclusion.  Аmong the Kirov region population standardized incidence of MM  is 1.8 cases per 100.000/year.  The  prevalence of MM in the Kirov region has a linear growth trend from 3 to 11 patients per 100.000 peoples within the analyzed period of observation 1994–2016. OS increased from 18 to 36 % in the period from 1994 to 2011. OS of MM patients has been increasing since 2006, due to using bortezomib-containing treatment options and autologous stem cell transplantation. In general, the 5-year OS increased from 18 to 36% in the period from 1994 to 2011.

Introduction. Autoantibodies directed against red blood cells (RBCs) are the main cause of hemolysis in patients with autoimmune hemolytic anemia (AIHA) and they can also complicate the course of certain diseases. Various methods are used to detect autoantibodies, but most of all, a polyand monospecific direct antiglobulin test (DAT) is applied. The method is based on the detection of immunoglobulins of G, M, A classes and С3 complement components bound with RBCs surfaces. DAT is used to differentiate between immuno-dependent and immuno-independent anemia. Objective of this study was the analysis of DAT results in patients with various diseases accompanied by anemia.

Materials And Methods. Blood samples of patients aged between 5 to 90 years with anemia who underwent examination and/or treatment at the Russian Research Institute of Hematology and Transfusiology of Russian Federal Medical-biological Agency were used as a study material. The results of laboratory testing for the period from 2013 to 2016 were examined and data analysis was performed. The determination of classes of antibodies directed against RBCs was carried out in a direct Coombs reaction using a gel system DiaMed-ID (DiaMed Micro Typing System, Switzerland).

Results. The DAT results were positive in patients with AIHA (53 %), paroxysmal nocturnal hemoglobinuria (PNH, 100 %), cryoglobulinemia (62.5 %), chronic lymphoproliferative diseases (CLPD, 27.5 %), multiple myeloma (MM, 23.6 %), anemia of unknown origin (21.4 %), and other autoimmune diseases (19 %). In blood samples of DAT-positive patients, monospecific IgG or C3 complement components, as well as various combinations of Ig with a complement component: IgG + C3, IgG + IgM + C3, IgM + C3, and IgG + IgA, were detected. In our study, positive DAT result was not always associated with laboratory evidence of hemolysis. Among all DAT-positive patients, signs of hemolysis were observed in 53.2 % of cases. Only in patients with AIHA and PNH hemolysis was observed in 100 % of cases.

Conclusions. A positive DAT result is one of the criteria for diagnosing of immune hemolytic anemia, however, it does not always indicate an autoimmune pathogenesis of anemia, the presence of specific autoantibodies, and thus is not always associated with hemolysis. Only a comprehensive assessment of a clinical picture and DAT results makes it possible to diagnose the disease.