Background. Acute myeloblastic leukemia (AML) with NPM7 mutation amounts to 30 % of all AML and is characterized by good prognosis with the exception of cases with FLT3-/TD mutation. Despite the good prognosis, the likelihood of relapses in patients with NPM7 mutation may significantly differ. Thus, the estimation of the minimal residual disease (MRD) after chemotherapy and during follow-up is becoming increasingly important. This approach will make it possible to predict the sensitivity of a tumoral clone to chemotherapy. Aim. To evaluate the prognostic value of highly specific marker (NPM7 mutation) and non-specific marker (WT1 overexpression) of MRD, as well as to identify the correlation between the levels of NPM7 and WT7 at different stages of therapy and in the follow-up period. Materials & Methods. The research included 14 patients with AML. All patients had the NPM7 mutation and WT7 overexpression: 50 % of patients had additional molecular markers (BAALC overexpression, FLT3-/TD, DNMT3A, and MLL mutations). Real-time PCR was used for long-term monitoring of WT7 expression levels and NPM7 mutation. Results. The median decrease of NPM7 levels after the induction therapy was 3 log. All patients had relapses, NPM7 mutation, and lower rates of OS/RFS, which significantly correlated with prognostically negative molecular markers. There were no statistically significant differences in RFS in groups with the decrease of WT7 expression level < 2 log and ≥ 2 log on day 28 of treatment. At the same time, the decrease of WT7 expression by > 2 log was associated with significant differences in early relapses, which correlated with the decrease of NPM7 levels (> and < than 3 log) is revealed. RFS rates were higher in patients with WT7 expression level of < 100 per 10⁴ copies ABL on day 28 and WT7 of < 250 per 10⁴ copies ABL on day 14 of treatment. WT7 expression was significantly lower on days 14 and 28 in patients with NPM7 decrease of > 3 log on day 28. The decrease in WT7 expression of < 100 per 10⁴ copies ABL on day 28 was more common in patients with isolated NPM1 mutation, compared to patients with additional negative molecular markers. Conclusion. The decrease in NPM1 levels after the induction therapy may serve as reliable prognostic marker of RFS and OS rates. New correlation between the degree of NPM1 reduction and the presence of additional molecular markers was established. Highly specific (NPM1 mutation) was shown to be more specific compared to non-specific markers ( WT1 overexpression). The research showed the predictive value of a lower limit level of WT1 on day 28 of treatment (100 per 10⁴ copies ABL), and for the first time, the importance of the early assessment WT1 expression reduction on day 14 of induction therapy.

Background. The current approach to treatment of acute myeloblastic leukemia (AML) includes the achievement of maximum tumor reduction and, therefore, eradication of a leukemic clone. The goal of the therapy is to achieve undetectable levels of the target gene, except an isolated molecular rearrangement of RUNX1-RUNX1T1. Aim. To estimate the dynamics of the RUNX1-RUNX1T1 level and relevant clinical manifestations during the monitoring of various stages of the program therapy and after its completion. Methods. The article presents a description of 10 cases of AML with isolated RUNX1-RUNX1T1 expression (n = 4) and the expression in combination with different molecular and cytogenetic abnormalities (n = 6). In addition, a long-term monitoring of the gene expression by quantitative determination of RUNX1-RUNX1T1 using a real-time PCR was presented. Results. The incidence of relapses in a group with a decreased RUNX1-RUNX1T1 expression level of >2 log is 75 % as compared to patients with a less significant reduction of the transcript level (with the relapse incidence equal to 0 %) (p = 0.05). The increase of the RUNX1-RUNX1T1 level against the background of bone marrow remission by more than 1 log coincided with a bone marrow relapse within 5-18 weeks. In addition, long-term persistence of a certain transcript level after the completion of a program therapy without relapse is possible. Conclusion. The study analyzed possible molecular background of different clinical outcomes of long-term persistence of the RUNX1-RUNX1T1 transcript that might lead to an individualized approach to AML patients.

Background. In patients with chronic lymphocytic leukemia (CLL) the eradication of minimal residual disease (MRD) is a prognostic factor of overall survival (OS) and progressionfree survival (PFS). IGHV mutational status has also independent prognostic value. Aim. To analyse the impact of mutational status and MRD eradication in CLL patients after first-line standard BR (ben-damustine + rituximab) immunochemotherapy. Materials & Methods. The prospective study included patients with immunophenotypically confirmed CLL who had not previously received anticancer therapy. All patients were treated by BR combination from 2012 to 2015. MRD level was determined in 109 patients after completing the 3^rd and the 6^th treatment courses. IGHV mutational status data were available for 98 patients. IGHV mutational status was evaluated in accordance with ERIC recommendations. MRD was assessed by standardized method of 4-color flow cytometry. Results. MRD negativity was achieved in 37 (34 %) out of 109 patients. MRD eradication correlated with the best PFS (p = 0.04). IGHV mutational status had a statistically significant impact on PFS (p = 0.02). In patients with MRD-nega-tive response and IGHV mutation no unfavorable events occurred during the period of monitoring. Conversely, PFS rates in MRD-negative patients having no IGHV mutation and in MRD-positive patients with mutation were significantly worse. MRD eradication resulted in statistically significant improvement of PFS rates after completing 3 treatment courses, compared with the cases with MRD persistence regardless of residual malignant clone level (p = 0.01). Conclusion. BR therapy as first-line treatment statistically improved PFS in patients who achieved MRD-negative remission after completing the 3^rd treatment course. PFS was significantly higher in MRD-negative patients with IGHV mutation after 6 treatment courses. MRD negativity resulting from 6 BR therapies in patients having no / GHV mutation was not accompanied by PFS improvement. It follows that by itself MRD negativity cannot be considered to be a universal prognostic factor.

Цель. Оценить эффективность режима FLAG/FLAG-Ida, выявить факторы, влияющие на достижение ремиссии, продолжительность безрецидивной (БРВ) и общей выживаемости (ОВ) у пациентов с рецидивами и рефрактерным течением острого миелобластного лейкоза (ОМЛ). Материалы и методы. В исследование включено 54 пациента (28 мужчин, 26 женщин), медиана возраста составила 37 лет (диапазон 18-70 лет). У 27 (50 %) из 54 пациентов имело место рефрактерное течение ОМЛ, у 27 (50 %)-рецидивы. В качестве индукционной терапии использовались режимы FLAG и FLAG-Ida. Трансплантация костного мозга выполнена 37 (68,5 %) пациентам. Молекулярно-генетическое и цитогенетическое исследования проводились до терапии и на 28-й день после ее начала. Уровень экспрессии гена WT1 оценивался на 14-16-й день лечения. Результаты. Полные ремиссии (ПР) достигнуты у 42 (77,8 %) из 54 пациентов. Рефрактерность к терапии наблюдалась у 9 (16,7 %) из 54 пациентов, летальность составила 5,5 % (3/54). Частота достижения ремиссии была выше при рецидивах ОМЛ в сравнении с рефрактерным течением ОМЛ-85,2 (23/27) и 70,4 % (19/27) соответственно. Пациенты с числом бластных клеток в костном мозге (КМ) ≥ 10 % на 14-16-й день терапии имели статистически значимо более низкий уровень достижения ПР (60 %) в сравнении с группой < 10 % бластных клеток в КМ (89,6 %; p = 0,024) и меньшую БРВ (медиана 7,6 vs 17,6 мес. соответственно; p = 0,03). Медиана БРВ у пациентов со снижением экспрессии гена WT1 < 1 log на 14-16-й день составила 5 vs 18 мес. у больных без этого снижения (p = 0,01). Показатели БРВ различались в группах пациентов с числом бластных клеток в КМ < 10 % на 14-16-й день терапии в зависимости от уровня редукции экспрессии гена WT1 (p = 0,04). Пациенты с МОБ

Background & Aims. The IGHV gene mutation status is a constant biological feature of tumor cells in chronic lymphocytic leukemia (CLL). This parameter is an important predictor of the efficacy of immunochemotherapy. It was included into the CLL international prognostic index CLL-IPI developed recently. The aim is to evaluate the prognostic significance of the BR regimen in patients with different variants of the B-cell receptor (BCR) structure. Methods. The study examined immediate and delayed treatment outcomes for 183 CLL patients included in a Russian, prospective, observational BEN-001 trial (NCT02110394). The median age was 61 years (range: 35-79); 53/179 (29.6 %) patients were older than 65; and 14/179 (7.8 %) patients were older than 75. Prevalence of males (110/179, 61.5 %) in the male/female ratio (1.6:1.0) was observed. Most patients had advanced disease: Binet B 116/173 (67 %) or Binet C 38/173 (22 %). The patients received the first-line therapy according to the BR regimen at standard doses in 36 hematological institutions in the Russian Federation over the period from 2012 until 2015. The genome DNA isolated from mononuclear leukocytes in the peripheral blood was used to assess the mutation status of the IGHV-genes. Results. The study demonstrated that unmutated CLL (> 98 % of homology to germline gene) is associated with worsening of the event-free and overall survival rates most of all; at that, the complete remission rate and the MRD-free survival rate were the same. Conclusion. It is reasonable to analyze the IGHV mutation status in all patients prescribed with the BR regimen as the first-line therapy.