Introduction. Acute leukemias are very rarely diagnosed during pregnancy, which makes large prospective or comparative studies of treatment of leukemias during pregnancy difficult. In 2009, the Russian Acute Lymphoblastic Leukemia Study Group decided to include women diagnosed with acute lymphoblastic leukemia (ALL) during various stages of pregnancy into the ALL-2009 prospective clinical study to determine the predictive role of pregnancy at diagnosis, and to estimate efficacy and tolerance of the ALL-2009 protocol in pregnant women.

Materials and methods. During the period of 2009– 2017, 15  pregnant women with Ph-negative ALL aged 18–41 (median 28) years were enrolled in the multicenter clinical trial ALL-2009 (NCT number NCT01193933). Eleven women were treated at the National Research Center for Hematology in Moscow; the other four were treated in Russian regional hospitals. In cases when ALL was diagnosed during the first trimester of pregnancy (n = 3), the pregnancy was terminated. If ALL was diagnosed at week 34–40 (n = 3), the baby was delivered before the beginning of therapy. If ALL was diagnosed during the second or early third trimester, the treatment was performed during pregnancy. We compared toxicity and tolerance of chemotherapy according to the ALL-2009 protocol in pregnant patients and in young (30 years and younger) ALL patients. We also compared the results of treatment of pregnant patients with the control group (127 women of fertile age: 16–50 years old, with a median of 28 years old) enrolled in the study. For discussion of the results, we did a meta-analysis of available publications (retrieved via PubMed using the keywords “acute lymphoblastic leukemia” and “pregnancy”).

Results. There was a significantly higher frequency of T-cell ALL than of B-cell ALL (53.3% vs 46,7% compared to 26% vs 69,3% in the control group, p = 0.025). Other than that, there were no significant differences in clinical or laboratory data between the groups. No significant differences were found in the duration of neutropenia, or in the duration and frequency of breaks in chemotherapy compared with other patients below 30 enrolled in the study. However, during the first remission induction phase, pregnant patients required blood transfusions, specifically platelets, at a higher rate (77.8% vs 46.6% of cases). Results of the treatment were similar regardless of pregnancy at the time of diagnosis (86.7% of complete remissions, vs 85.8% in the control group). Differences in the frequency of refractory leukemia (13.3% vs 4.7%) were not statistically significant. There were no cases of early mortality. Long-term results were also similar, both in terms of overall survival (58.6% vs 43.3% in the control group) and in terms of disease-free survival (46% vs 51%). Relapse probability was the same (49% vs 40.3%). Overall, the pregnant patients gave birth to 12  children (6 boys and 6 girls) at weeks 34–38 (median 35 weeks) of pregnancy. At the time of writing, all children are healthy and are developing in accordance with their age, which ranges from 2 years 1 month to 8 years 10 months (median 5 years and 2 months).

Conclusion. The results of the study suggest that pregnancy at the time of diagnosis with ALL did not affect either the short-term or the long-term results of therapy according to the ALL-2009 protocol. The acceptable level of toxicity of the low-dose cytostatic therapy for both the mother and the child makes it possible to use the ALL-2009 protocol in treatment of pregnant patients.

Introduction. Massive transfusions of allogenic erythrocytes boost risk of post-transfusion reactions and complications for recipients, among them most severe are the immune hemolytic complications. Ensuring the safety of blood transfusion maintenance of high-tech operations on the heart and blood vessels is an important task.

Objective: An analysis of the distribution of erythrocyte antigens of AB0 and RH systems among patients and the incidence of anti-erythrocyte antibodies. Materials and methods. 13,948 patients’ blood samples were examined in 2014— 2016. In the first half of 2017, antibodies (secondary screening) were further examined on days 5—7 and 12—14 after blood transfusion of 51 patients with massive transfusions and/or transfusions of donor RBC containing at least one antigen not found in the recipient’s (C, c, E, e). Immunological studies and selection of a donor-recipient pairs were performed by highly sensitive methods in gel cards of the diagnostic system Diagnostic Grifols SA (Spain).

Results. The study showed that the use of the gel technique in antibodies screening increases their detectability by several times (from 0.15% to 0.75%). There were no significant differences in the distribution of AB0 blood groups between immunized and nonimmunized patients. The greatest number of alloimmunized patients is at the age from 50 to 70 years. Immune alloantibodies are more often detected in women (1.10%) and Rh-negative patients than in men (0.55%) and Rh-positive patients (0.45%). The study did not reveal the production of alloantibodies in patients on days 5—7 and 12—14 after blood transfusion , even at transfusion of RBC with nonshared antigens (C, c, E, e).

The conclusion. It is desirable to investigate the presence of anti-erythrocyte alloantibodies before each blood transfusion, especially if blood transfusion is performed later than 12—14 days after the previous one. It is advisable to keep medical records (an extract from the hospital) with the data on the transfusions of donor erythrocyte-containing medium with the indication of their phenotype. 

Background. Currently, in-depth analysis of the results of sequencing outside the coding sequences of the ТР53 gene is absent, the number and functional effects of aberrations detected in them are underestimated. The purpose of this study was to identify changes in non-coding regions of ТР53 in tumor tissue of diffuse large B-cell lymphoma (DLBCL) and to predict the possible consequences of these changes.

Material and methods. Genomic DNA was isolated from paraffin blocks of biopsies of tumor lymph nodes and extranodal lesions of 92 patients with DLBCL. The nucleotide sequence of the coding region of ТР53 (exons 5—10) and adjacent introns, as well as the fragment of the 3’-UTR gene sequence containing the polyadenylation signal, was determined by direct capillary sequencing by Sanger method. Theoretical prediction of possible consequences of detected intron mutations was carried out using the program NetGene2.

Results. In tumor material from 74 patients with DLBCL, 12 types of mutations in intron sites were identified: g.7675266A>G, g.7675010C>A, g.7674988A>G, g.7674326C>G, g.7674153C>G, g.7673691G>T, g.7673681T>C, g.7673664T>C and g.7673523A>G. The mutation  I g.7674326C>G, which has proven biological significance from in vivo experiments, according to The Human Cancer Mutation Database refers to changes that affect splicing. According to the prognosis of NetGene2, from intron replacements revealed by us in the group of patients, g.7675010C>A leads to the formation of an additional acceptor site for splicing, which may result in the incorporation of a part of the intron 5 into the mRNA sequence. In 5/9 cases of detection of rs78378222 in samples of tumor tissue of DLBCL, a homozygous minor genotype C/C was determined, which indicated the loss of heterozygosity in this locus, which contributes to a significant increase in malignant cell potential.

Conclusions. Thus, the data obtained by us testify to the functional selection at the stages of the tumor progression of DLBCL changes not only in the coding but also introns and 3’-UTR ТР53 gene. 

In the 1990s, two gene polymorphisms — factor V Leiden (FVLeiden) and prothrombin G20210A (FII G20210A) were recognized as a genetic substrate for the development of thrombophilia. Polymorphism FVLeiden is associated with the development of resistance to anticoagulant action of protein  C, and polymorphism FII G20210A with a high level of prothrombin in plasma. In healthy individuals of Caucasian origin, the prevalence of FVLeiden is between 2 and 10%. In patients with venous thromboembolism, the prevalence FVLeiden is about 20%. FII G20210A is found in 1—5% of the general Caucasian population and in 4—18% of patients with venous thromboembolism. These indicators depend on the selection of patients included in the analysis. The relationship between gene polymorphisms and the development of venous thromboembolism in women during pregnancy is discussed. The high risks of venous thromboembolism have been described for women with a homozygous FVLeiden mutation. The study of the activated protein  C (APC) and factor  V interaction has yielded valuable insights into how perturbations in this association lead to venous thromboembolism. It is now clear that APC exerts anticoagulant effects beyond inactivating factor  V by cleaving at R306 and R506, generating inactive FV. Mutation in FVLeiden abrogates this effect. In women with a heterozygous FVLeiden or heterozygous FII G20210A, the risks of venous thromboembolism are significantly low. Regardless of genetic polymorphism, a positive family history of venous thrombosis increases the risk of developing venous thromboembolism during pregnancy. The relationship between genetic polymorphism and nonthrombotic complications developing during pregnancy is discussed. Mutations of FVLeiden and FII G20210A may be associated with the risks of spontaneous abortion and repeated fetal loss.

Pseudotumors are rare complication in hemophilia patients, occurring in 1—2% of cases. The triggering mechanism of pseudotumor development is hematoma, which can transform into pseudotumor when the treatment is differed or not full. The most severe complication of pseudotumor are destruction of underlying tissues, infection and spontaneous dissection of the pseudotumor and the development of uncontrolled bleeding. Often pseudotumors are confused with malignant neoplasms, which leads to errors in the algorithms of examination and treatment of patients with hemophilia and pseudotumors. Therefore, the clinical case of treatment of giant pseudotumors of multiple localization at patient with an inhibitory form of hemophilia seems to be of interest.

Here is a description of a medical case of continuous use of vorinostat when treating a patient with mycosis fungoides, depiction of observed side effects and practice of combining the drug with other antineoplastic agents.

Specialists-hematologists constantly need to update their knowledge in connection with the rapid development of hematology and the introduction of new methods of diagnosis and treatment into practice.

Recommendations for the diagnosis and therapy of Rhnegative myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, primary myelofibrosis, unclassified myeloproliferative disease, postpolycythemia and postthrombocytemic myelofibrosis) are developed by the research group for studies of myeloproliferative diseases at the initiative of the Russian National Hematological Society (Chairman: Prof. V. G. Savchenko, Chief Extraordinary Expert for Hematology of the Ministry of Health of Russia, Academician, Director General of the National Research Center for Hematology).

The aim of these recommendations is standardization of the diagnostic and therapeutic approaches in Russia. The methodological approaches are based on the recommendations of the Russian expert council (leading specialists of 10  hematological centers of the Russian Federation) for diagnosis and treatment of patients with classical Ph-negative myeloproliferative neoplasms, Russian experience in management of patients and diagnostic criteria approved by WHO in 1017 and the recommendations of the European Leukemia NET (ELN), National Cancer Control Net (NCCN; USA), International Working Group for Myeloproliferative Neoplasm Research and Treatment (IWG-MRT).

The draft clinical guidelines were reviewed on November 11, 2013 at a meeting of the Expert Group on Myeloproliferative Diseases. The discussion was attended by leading experts of 10 hematology centers in Russia. The project was approved at the meeting of the Profile Commission on the specialty “Hematology” on March 3, 2014. At the II Congress of Hematology on April 12, 2014, clinical guidelines for the diagnosis and treatment of classical Ph-negative inventories were approved.

Clinical guidelines are a dynamic document. National Clinical Guidelines for the diagnosis and treatment of classic Ph-negative myeloproliferative diseases are updated once every two years. In 2017 clinical recommendations approved at the III Congress of Hematology of Russia on April 15, 2016 were published. This edition is an updated version approved at the IV Congress of Hematology of Russia on April 13, 2018.

The recommendations are intended for hematologists, chemotherapists, health administrators, medical students.