ORIGINAL ARTICLES
The tasks of the Russian multicenter randomized trial of AML-10 were to evaluate of the efficacy of 2 consolidation courses – either (1st branch) with standard dose Cytarabine (7 + 3), or (2nd branch) – at the high dose (HiDAC 1 g/m2, twice a day, 1–3 days) in combination with Idarubicin (8 mg/m2, 3 days) and mitoxantrone (10 mg/m2, 3 days); after administration of 2 courses of induction 7 + 3 with Daunorubicin in a dose of 60 mg/m2 on the introduction and subsequent maintenance therapy by 6 courses 5 + 5 (Cytarabine +6MP).
Material and methods. From January 2010 to January 2013 250 AML patients were included in the trial from 20 Hematological Centers of theRussian Federation. 125 of 250 patients (73 women and 52 men) aged 17 to 59 years (mean age: 45 years) were randomized to the 1st branch of therapy and 125 patients (69 women and 56 men) aged between 16 and 60 years (mean age: 43 years) – to the 2nd branch. 212 patients were included in the analysis carried out in September 2015 (there is no data about 39 patients). Cytogenetic data are presented in 75% of patients: in the 1st branch 17.3% of cases were referred to favorable group on cytogenetics, 66.7% cases – to the intermediate risk, and 16% cases – to the negative risk; 2nd branch – 20; 53.6 and 21.4% respectively.
Results. Achievement of complete remission (CR) was observed in 153 (72.2%) of patients, the resistance was in 28 (13.2%), death occurred during induction in 31 (14.6%), death in complete remission – in 22 (14.4%). Five year overall survival rate (OS) was 30.7%, disease-free survival (DFS) rate was 32.7%. There was no difference in OS and DFS in patients in the 1st and 2nd branch of treatment: 31.6 and 29.8%; 39.6 and 25.8% respectively. Upon achievement of CR after the 1 cours DFS in the 1st branch was in 44%, in the 2nd branch – 31%. After the 2nd course – 34 and 20%. In multivariate analysis (MA, Cox model), including gender, age, randomization option, initial leukocytosis and platelet count, the percentage of blast cells in the peripheral blood and bone marrow, risk for cytogenetics, albumin and LDH, achievement of CR after the 1st or 2nd course, the performance of allogeneic HSCT in the 1st CR, there were identified factors statistically significantly negative affected on the indices of 5-year OS and DFS: unfavorable cytogenetic group (HR 1.9; p = 0.014 and HR 3.047; p = 0.0049, respectively), achievement of CR after the 2nd course (HR 2.4; p = 0.003 and HR 2.3; p = 0.007) and the non-performance of allogeneic HSCT in the 1st CR (HR 4.71; p = 0.001 and HR 4.9; p = 0.006).
Conclusion. Consolidation HiDAC has no advantage over consolidation with standard doses Cytarabine in using a high cumulative dose of anthracyclines. High-dose consolidation does not improve long-term survival results in patients from the various risk groups: in the achievement of CR after the 2nd course and from the intermediate /unfavorable risk group for cytogenetics. Upon reaching the CR after the 2nd course of chemotherapy just the performance of allogeneic HSCT allows you to get long-term results that are comparable with those in groups of favorable prognosis.
Monosomal karyotype is the extremely poor variant of chromosomal aberrations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Retrospective analysis of 43 AML and 33 MDS patients was performed to determine typical clinical and hematological features of chromosomal karyotype. No characteristics typical for monosomal karyotype were found. Median of overall survival of AML and MDS patients was 6 and 8 months accordingly. At the same time some patients had relatively favorable course of their disease.
Current methods of the laboratory diagnostics permit to detect a large quantity of the molecular markers, typical for patients with acute myeloid leukemia. However, low frequency of some aberrations does not not to determine their prognostic value. Thus, the necessity of the selection of the most frequent and prognostically significant molecular markers specifies the actuality of the present research. We analyzed the incidence and prognostic relevance of NRAS, CKIT, FLT3 and NPM1 mutations in 200 AML patients. Cytogenetic and molecular-genetic analysis was carried out by GTG-method, PCR and sequencing. We found out, that mutations in CKIT, FLT3 and NPM1 significantly influence on the prognosis, thereby the algorithm of genetic diagnostics of AML patients was suggested. We underlined the importance of the detection of simultaneous mutations in genes with different functionality.
The possibility of destruction or structural changes of tumor cells exposed to short (microsecond range) shock-wave pulses was investigated. It was shown that changes in the structural organization of the nuclear chromatin were observed under the influence of shock-wave pulses of microsecond range on large tumor cells. The effect of tumor cells damage was achieved, normal cells remained to be intact.
The rate of the detection of the markers of the Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency Virus 1 and 2 types (HIV-1/HIV-2) among donors of plasma for fractionation over the period of 2012--2013 was evaluated. The incidence rate of markers of hemotransmissible infections (HTI) among donors of plasma for fractionation amounted for HIV-1/HIV-2: 0.03–0.07%, for HBV: 0.15–0.21% and for HCV: 0.35–0.37%. These indices are 1.5–2 times lower than the all-Russian indices, obtained from the results of activity of the blood service in 2012 and2013. Inthe group of "approved donors" markers of HIV-1/HIV-2, HBV and HCV were detected significantly less often (more than 10, 20 and 23 times, respectively) than among potential plasma donors. There was performed an epidemiological evaluation of the population of donors of plasma for fractionation in conformity with the standards of Plasma Protein Therapeutics Association (PPTA). The data obtained testify to the efficiency of the introduced system of qualification of donors of plasma for fractionation. The introduced system provided a level of infectious safety of stored plasma complying with international industry standards of quality – PPTA.
Objective. To analyze the differences in the hemostais at patients with acute pancreatitis
Materials and methods. In 25 patients (mean age: 46,2 ± 6,74 years); partial thromboplastin time (APTT), prothrombin time (results expressed as INR), thrombin time, fibrinogen concentration, the concentration of D-dimer, protein C, protein S, plasmin inhibitor, plasminogen and von Willebrand factor (vWF), the activity of antithrombin III, hemoglobin concentration (Hb), hematocrit (Ht), number of erythrocytes (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MCH), mean corpuscular hemoglobin concentration (MCHC), the width of the distribution by volume of erythrocytes (RDW), platelet count (PLT) value trombocrit (PCT), mean platelet volume (MPV), platelet distribution width by volume (PDW) were evaluated. Statistical processing. The data were treated with the use of the exact one-sided Mann–Whitney test, sign test and Wilcoxon rank sign test.
Results. In patients with acute pancreatitis there were identified significant changes in platelet, coagulation, fibrinolytic and anticoagulant mechanisms.
Conclusion. The reduction in the activity of antithrombin, protein C and plasminogen was noted in the group of died patients.
Sequence based typing was used to identify human leukocyte antigen HLA-A, HLA-B, HLA-C, HLA-DRB1, HLADQB1 alleles from 2444 donors residing in the Chechen Republic and the Republic of Dagestan, Russia, for unrelated hematopoietic stem cell registry. During the performance of the research in the study population there was identified new allele, which was not previously registered on The WHO Nomenclature Committee for Factors of the HLA System. In this population, 51 HLA-A alleles from 19 groups of alleles were detected. Alleles occurred with the frequency more than 10% included HLA-A*02:01 (32.28%), 01:01 (11.54%), 24:02 (10.84%). New identified allele HLA-A*24:314 (0.31%) ranks second in the frequency of alleles among the allelic group A*24, after allele A*24:02.
REVIEWS OF LITERATURE
There are presented data of the literature about the structure and function of the opened at the end of XX century the genes of the MIC locus, characterized by high polymorphism. They play an important role in cell-cell interactions involved in the implementation of responses of the innate and adaptive immunity as ligands for the NKG2D receptors expressed on different subpopulations of T-lymphocytes. There is relationship between MIC locus genes with diseases and their impact on the outcome of transplants. Population characteristics and distribution of MICA and MICB alleles are described.
This review is devoted to the problem of the neurotoxicity of chemotherapeutic agents. Peripheral neuropathy induced by chemotherapy is the specific manifestation of the neurotoxicity affecting both on the life quality of patients with oncologic pathology and possibility of the chemotherapy prescription. The toxic influences on the peripheral nervous system of chemotherapeutic agents (taxanes, epothilones, platinum compounds, vinca alkaloids, binding of growth factor inhibitors, proteasome inhibitors, immunomodulatory agents) are described. Against the background of peripheral neuropathy induced by chemotherapy there is the damage of peripheral motor, sensory and autonomous neurons, characterized by various abnormalities as follows: sensory (tingling, numbness, pain), motor (muscular delicacy, paresis) and autonomic (digestive tract motility disturbances, arrhythmia), and neuropathic pain.
Mast cell leukemia is characterized by proliferation and accumulation of immature mast cells in the bone marrow and other organs. The difficulties exist in the differential diagnosis of leukemic systemic mastocytosis and myelomastocytic leukemia. Although in both cases diagnostic criteria are reported, some questions about the terms remain to be open. This problem was discussed by the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) in 2011--2013. The diagnosis of myelomastocytic leukemia as myeloid tumor with a large number of mast cells was proposed as eligible in the absence of diagnostic criteria of mastocytosis. It was also recommended to divide leukemic systemic mastocytosis into acute and chronic forms based on the presence or absence of cutaneous manifestations. The primary form of the mast cell leukemia must be differentiated from the secondary, which usually develops in the set of aggressive systemic mastocytosis and mast cell sarcoma. The authors put emphasis on the inevitability of the prephase or leukemic systemic mastocytosis, which is often debut as aggressive systemic mastocytosis with rapid progression and the appearance of from 5 to 19% of mast cells in bone marrow smears. This condition is recommended to call the aggressive systemic mastocytosis in conversion to mast cells leukemia. The expansion of the current WHO classification by incorporating different variants of mast cell leukemia, will optimize the selection of patients for clinical trials.
ISSN 2411-3042 (Online)