Objective. Data analysis of the register of patients with invasive aspergillosis (IA), which was founded in Saint Petersburg (1998–2017), and clinical case description of successful treatment of IA and mucormycosis with lungs involvement in a patient with Hodgkin’s lymphoma.

Materials and methods. In the study were included 29 oncohematological patients with IA and mucormycosis. In control group were included 483 oncohematological patients with IA. We used criteria EORTS/MSG, 2008 for IA and mucormycosis diagnosis.

Results. We identified that the combination of IA and mucormycosis significantly often develops in patients with acute lymphoblastic leukemia (32 %, р = 0.001), and allogeneic hematopoietic stem cells transplants (allo-HSCT) recipients (52 %, р = 0.001). In mixed-infection Aspergillus nidulans was frequent IA etiological agent (11 %, р = 0.001). The main mucormycosis etiological agents were Rhizopus spp. (45 %), Lichtheimia corуmbifera (20 %). The main sites of the localization were lungs (76 %), disseminated process and paranasal sinuses involvement were identified more frequently (45 % and 17 % (р = 0.0001; р = 0.002), respectively). Typical clinical feature of IA and mucormycosis combinations was hemoptysis (24 %, р = 0.008), radiological signs – lesions with cavities destruction (38 %), hydrothorax (29 %) and a “reverse halo” symptom (17 %). Antifungal therapy received 76 % of patients, surgery – 34 %.

Conclusion. Mucormycosis was revealed in 5.7 % of patients with IA. The main risk factors for co-infection are allo-HSCT, long-term agranulocytosis, lymphocytopenia and glucocorticosteroid therapy. Overall 12 weeks survival in patients with mixed-infection was 38 %, significantly lower than in patients with IA (р = 0.005). An unfavorable prognosis factor was dissemination of mycotic infection (р = 0.009).

Currently we are facing a revolution in therapy of chronic lymphocytic leukemia, related to the development of novel target drugs, which have markedly improved treatment results in all groups of patients. While inhibitors of Bruton’s tyrosine kinase (ibrutinib, acalabrutinib etc.) and phosphatidylinositol-3 kinase isoforms (idelalisib, umbralisib etc.) are currently in the spotlight, much less attention is paid to antiapoptotic protein inhibitors such as venetoclax. In this review we summarize the results of venetoclax clinical studies in CLL as monotherapy and in combinations. The drug is distinguished by a high rate of complete responses and minimal residual disease eradication in high risk CLL patients, as well as a favorable toxicity profile. This makes it an ideal component of non-genotoxic regimens, aimed at the cure of the disease.

Angioimmunoblastic T-cell lymphoma is a rare T-cell lymphoproliferative disease with generalized lymphadenopathy, hepatosplenomegaly, intoxication and polyclonal hypergammaglobulinemia. The persistence of plasma cells in peripheral blood can be a manifestation of both tumor and reactive processes. In our article, we described the case of angioimmunoblastic T-cell lymphoma with an increase in the number of peripheral blood plasma cells to 28 %, and in bone marrow to 9 %. The complex diagnostics, including plasma cells immunophenotyping, morphology of the lymph node biopsy and bone marrow samples, made it possible to verify the diagnosis of angioimmunoblastic T-cell lymphoma with polyclonal plasmacytosis.

Introduction. Surface immunoglobulin expression is a main immunophenotypic criteria of mature subtype of B-lineage acute lymphoblastic leukemia. Although the majority of such cases represents Burkitt leukemia/lymphoma, it was shown for several times that membrane IgM could be detected in the absence of other mature lymphomas signs.

The aim of the study was to evaluate heterogeneity of childhood acute lymphoblastic leukemia (ALL) with surface IgM expression and to assess correspondence of BIV EGIL ALL subtype with Burkitt lymphoma (BL) bone marrow dissemination.

Materials and methods. Immunophenotypic, cytomorfologic and genetic data of 54 BIV-ALL cases were analyzed.

Results. Among the studied patients 39 had BL, while others belonged to B-cell precursor ALL (BCP-ALL). All BL patients and none of BCP-ALL patients carried C-MYC rearrangement while in BCP-ALL group in 8 cases and in any BL cases KMT2A rearrangements were found. None of BCP-ALL children had L3 morphology according to FAB classification.

Conclusions. B-lineage ALL with surface IgM expression is rather heterogeneous group of cases including typical BL and rare cases of BCP-ALL even with KMT2A-rearrangements. Combination of all available diagnostic technologies will allow precise split of these two different disease and select the appropriate treatment scheme.

Introduction. Аngioimmunoblastic T-cell lymphoma (AITL) is a T-cell lymphoma, characterized by abundant polymorphocellular infiltrate of lymph nodes with the small number of tumor CD4⁺ T-cells. AITL could often be misdiagnosed as reactive processes and other lymphomas, including Hodgkin’s lymphoma. Molecular methods of determining clonality are used to confirm the diagnosis. TCR gene rearrangements detected in the lymph nodes may not coincide with those detected in the bone marrow (BM), blood or skin, that makes their interpretation difficult. Recently discovered point somatic RHOA (Ras homolog gene family, member A) Gly17Val mutation is present in 53–71 % of angioimmunoblastic T-cell lymphomas.

The aim of the study was to evaluate the number of RHOA Gly17Val mutated cells in different tissues of AITL patients and to correlate it with corresponding T-cell clonality results.

Materials and methods. TCRG and TCRB gene rearrangements were PCR-amplified according to BIOMED-2 standardized protocol and analyzed by capillary electrophoresis on ABI Prism 3130. Gly17Val mutation was analyzed by quantitative allele-specific (qAS) TaqMan Real-Time PCR assay. Lymph nodes (LN) and skin biopsies, blood and BM samples were studied for 40 patients with AITL.

Results. The clonal TCR gene rearrangements were found in 37 (92 %) of 40 patients in LN and in 26 (96 %) of 28 patients in BM, but they were not matched in length in LN and BM in 12 (46 %) of 26 patients. RHOA (Gly17Val) mutation in LN was revealed in 60 % (24 of 40) patients. Number of cells with RHOA mutation was highest in the LN (in average 26.7 % of the total cells), while in the BM RHOA mutation were undetectable (in 7 patients), or detected in 10 patients in a low quantity (in average 2 % of the total cells). Skin, blood and BM samples with the T-cell clonality peaks that differ from those found in the LN were also negative for the presence of cells having RHOA Gly17Val mutation. Also, in four patients we showed that clonal products in BM and blood that do not coincide with LN refer to CD8+ lymphocytes.

Conclusions. The results of the study demonstrate that the quantitative determination of cells with the mutation of RHOA Gly17Val must be taken into account in staging the disease and interpreting the results of T-cell clonality assay. Clonal cells with rearrangements not matching those identified for the LN should be considered reactive.

The renin-angiotensin system (RAS) has long been known as the endocrine system involved in the regulation of arterial pressure and waterelectrolyte balance. Local (tissue) RAS can influence cellular activity, tissue damage and regeneration. In the bone marrow there are active ligands of peptides, mediators, receptors and signaling pathways of the RAS. Local RAS can influence the growth, production, proliferation and differentiation of hematopoietic cells and participate in the regulation of both normal and pathological hematopoiesis. Angiotensin-converting enzyme (ACE) CD143 plays a key role in the classical RAS. After differentiation from hemangioblast, hematopoietic progenitor cells constantly express ACE in human embryonic, fetal and adult hematopoietic tissues, as well as at all stages of hematopoietic ontogeny. The ACE cleaves the C-terminal dipeptide and thus forms the octapeptide Angiotensin II. In addition to angiotensin II, ACE also regulates a group of biologically active peptides, such as substance P, ac-SDKP and angiotensin 1–7. Local RAS is also one of the most important components in the tumor microenvironment, affecting tumor growth and metastasis by autocrine and paracrine pathways, modulating numerous carcinogenic events such as angiogenesis, apoptosis, cell proliferation, immune responses, and extracellular matrix formation.

The purpose of this review is to describe the known functions of local RAS in the hematopoiesis regulation. More detailed study of the RAS components mechanisms of action will expand therapy approaches in the neoplastic diseases and in bone marrow transplantation.

Introduction. Translocation t(12;21)(p13;q22) is one of the most common structural genetic abnormalities in childhood acute lymphoblastic leukemia (ALL). It cannot be detected by conventional G-banding, so a reverse-transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization are used for this purpose.

The aim of the study was to evaluate the prognostic significance of qualitative and quantitative detection of ETV6-RUNX1 fusion gene transcript at various time points in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients.

Materials and methods. ETV6-RUNX1 fusion gene transcript was revealed by both reverse-transcriptase PCR and quantitative real-time PCR (RQ-PCR) in 34 out of 166 (20.5 %) children with BCP-ALL. Qualitative ETV6-RUNX1-positivity at days 36 and 85 led to unfavorable outcome (lower event-free survival –EFS and higher cumulative incidence of relapse – CIR). While ETV6-RUNX1 status at day 15 did not allow to divide patients with different outcomes. By ROC curve analysis we determined threshold levels (TL) for ETV6-RUNX1/ABL1 ratio at days 0, 15, 36 and 85. Afterwards we adjusted obtained results to 10-fold scale.

Results. So practically applicable TL were as follows 500.0 %, 1 %, 0.1 % и 0.01 % for days 0, 15, 36 and 85, respectively. EFS and CIR were both worse in patients with ETV6-RUNX1/ABL1 ratio equal or above defined TL. Moreover, initial ratio ≥500,0 % corresponded to delayed blast clearance at days 15 and 36. We showed good qualitative (84.8 %) and quantitative (R² = 0.953) concordance between ETV6-RUNX1/ABL1 ratio and MRD data obtained by flow cytometry at days 15, 36, 85. Of note, defined TL for ETV6-RUNX1/ABL1 at days 15, 36, 85 were equal to prognostically important levels for flow cytometry MRD.

Conclusion. Thus, qualitative detection and quantitative value of ETV6-RUNX1 fusion gene transcript showed prognostic significance in the course of treatment in children with BCP-ALL. Based on these results we propose standardization approaches for Moscow – Berlin ALL study group.