Aim. To assess the rate of DNMT3A, IDH1, IDH2, and ASXL1 gene mutations and their effect on the prognosis both as isolated findings and in combination with well-known chromosomal aberrations and gene mutations in newly diagnosed acute myeloid leukemia (AML) patients from some regions of the Russian Federation. Materials & Methods. The study enrolled 83 patients with newly diagnosed AML from 22 regions of the Russian Federation, who underwent molecular genetic examination for detecting IDH1 (R132), IDH2 (R140), ASXL1, and DNMT3A gene mutations with droplet digital PCR and Sanger sequencing methods. Results. The mutation rate in DNMT3A was 16.7 %, in IDH1 (R132) it was 6 %, in IDH2 (R140) it was 9.6 %, and in ASXL1 it was 6 %. The R140 mutation in IDH2 correlated with the older age of patients. The mutations in IDH1 (R132), IDH2 (R140), and DNMT3A showed a significant association with mutated NPM1. The mutations in IDH1 (R132), IDH2 (R140) were reported to occur significantly more often in patients with normal karyotype. The IDH1 (R132) and IDH2 (R140) mutations appeared to have a favorable effect on AML prognosis, which is most likely to be associated with a high rate of their compatibility with NPM1 mutation. The mutated type of DNMT3A had a negative effect on overall survival of patients with NPM1 mutation. The mutation in ASXL1 also appeared to be an unfavorable prognostic factor for overall survival of patients with wild type NPM1. Conclusion. A high rate of mutation occurrence in epigenetic regulation genes as well as the prognostic potential of these mutations in AML necessitate the need for determining the mutation status of DNMT3A, IDH1, IDH2, and ASXL1 in the context of primary diagnosis in real-world clinical practice.

The publication contains materials of the reports presented at the II Conference “Current Issues of Diagnosis and Treatment of Ph-Negative and Ph-Positive Myeloproliferative Neoplasms” held from 15 to 16 March 2019 at the National Research Center for Hematology (Moscow). The conference was organized to enable professional communication of the clinicians specializing in the treatment of myeloproliferative neoplasms (MPN), and the researchers in the related fields as well as to allow the exchange of views on the implementation of current diagnosis and treatment methods in Ph-negative and Ph-positive MPNs. Reports covered a wide range of rare and non-standard settings. Of particular importance was the opportunity to debate them in detail at panel discussions and interactive sessions. This format of the conference allowed to provide expert opinions in the present publication. It emphasizes the importance of complex diagnosis in MPN using morphological examination of bone marrow core biopsy samples and molecular genetic testing. Accordingly, the second day of the conference was devoted to a thorough analysis of the morphological characteristics of the cases presented and based on bone marrow core biopsy samples.

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.

Imatinib has shown the high effectiveness in chronic myeloid leukemia (CML) therapy. Recent papers have demonstrated that the achievement of complete cytogenetic response and major molecular response to imatinib therapy may be related with more than 1000 ng/ml imatinib plasma level. Trough plasma concentrations of imatinib (Ctrough) were detected in 551 samples of 442 CML patients. Blood samples were collected 24 b 3h after the last IM dose at 300 (n = 8), 400 (n = 337), 600 mg (n = 155) QD and 12 b 3h after the last IM dose at 800 mg BD(n = 51). Imatinib plasma concentration was determined by a validated LC/ MS/MS method. Rationales for imatinib blood level testing: the patient is not responding as well as the physician would expect, the physician suspects that the patient may be nonadherent to imatinib, the physician suspects that the patient may be experiencing a drug-drug interaction, the patient is experiencing unusually severe side effects. A result of nonadherence to treatment is one of the most important reason of treatment failure or suboptimal response to imatinib (n = 32; 5.8 %). The level of noncompliance increases with higher imatinib doses. Imatinib trough plasma level less than 1000 ng/ml were founded in one half of cases.