Follicular lymphoma (FL) refers to indolent mature B-cell lymphomas and, despite the recurrent course, is generally characterized by a favorable prognosis with long-term overall survival. However, in about 20 %, the disease has an aggressive course with early progression and 5-year overall survival of only 50 %, which indicates the biological heterogeneity of FL. Due to the extremely poor prognosis, cases with disease progression within 2 years from the start of treatment represent a major clinical problem.
What predictive risk models of FL early progression are available to us and what regimens of the second and subsequent lines of anticancer therapy should be used? Is high-dose consolidation necessary and when?
Choosing the optimal therapy in early progression of FL is a complex task and depends both on the variant of the previous treatment and the patient’s status, as well as the objectively available therapeutic options. In the case of FL early progression after immunochemotherapy, an alternative regimen is used based on a previously unused anti-CD20 monoclonal antibody (rituximab or obinutuzumab) and non-cross-acting chemotherapeutic agents. For CHOP-like induction therapy, the optimal second-line drug is bendamustine. In addition to cytostatics in combination with anti-CD20 monoclonal antibodies, new agents are currently actively used in FL therapy (such as immunomodulators, inhibitors of B-cell receptor and histone methyltransferase signaling pathways, BCL-2 inhibitors, etc.). Numerous clinical trials continue to actively search for promising therapeutic options for the treatment of FL, with testing of new drugs to other B-cell targets and with different mechanisms of action.
We present a clinical case of FL with early generalized progression, ineffectiveness of subsequent intensification of treatment with autologous hematopoietic stem cell transplantation and the choice of salvage therapy in the realities of 2009–2012.

Acute leukemia (AL) in children up 1 year old is very rare disease, comprise less 5 % of all pediatric AL cases. The clinical course of infant AL is extremely aggressive with frequent extramedullar dissemination, initial hyperleukocytosis and MLL aberrations. Predominance of unfavorable clinical and laboratory features leads to unsatisfactory treatment results by modern curative protocols in children up to 1 year old: 4-year event-free survival for acute lymphoblastic leukemia is 50.9 ± 4.5 % and 3-year event-free survival for acute myeloid leukemia – 72–74 %.
Optimization of therapeutic programs for infant AL with consideration to anatomy and physiologic features of infants, inclusion of targeted drugs (blinatumomab), epigenetic and cell technologies is actual and not resolved problem in modern pediatric oncology-hematology.

JAK2 mutations can be associated with any phenotypic form of chronic myeloproliferative neoplasia, while MPL and CALR mutations occur, as a rule, in cases of essential thrombocythemia and primary myelofibrosis and they are not observed in polycythemia vera. In this article we describe a clinical case of CALR mutation (c.1154_1155insGTGTC; p.E386fs*46) presence in a JAK2-negative polycythemia vera patient at age 36. In January 2018 changes in his hemogramm were recorded for the first time. In June 2018, based on a diagnostic study of bone marrow trepanobiopsy, a diagnosis of polycythemia vera was made. Molecular genetic study of the patient’s DNA didn’t reveal mutations in the JAK2 (12 and 14 exons) and the MPL genes. CALR mutation was revealed during the screening by heteroduplex analysis with the electrophoresis in polyacrylamide gel. Then the mutation was identified by Sanger’s DNA sequencing as с.1154_1155insGTGTC; p.E386fs*46. The allelic burden level as determined by pyrosequencing was 20 % (June 2018). In conclusion we can suppose that the revealed CALR mutation с.1154_1155insGTGTC; p.E386fs*46 plays its role in our patient’s polycythemia phenotype.

A rare case of anaphylactic shock after administration of 4^th generation recombinant blood coagulation factor VIII is presented. Anaphylactic shock is a life-threatening complication for a patient with hemophilia A. Temporarily refrain from re-administration of factor VIII, a skin test confirming drug choice, and a patient desensitization procedure provide the clinician with a chance to continue hemostatic replacement therapy for a patient with hemophilia A.
The main purpose of this case report is to determine the algorithm of actions to overcome the consequences of anaphylactic shock and continue the prophylactic administration of coagulation factor VIII concentrate to prevent bleeding in a child with a rare random combination of an anaphylactic reaction and congenital coagulation disorders.

Acute myelomonocytic leukemia is a rare form of leukemia, in which the bone marrow is damaged by morphologically immature, tumor cells, which subsequently displace the normal cellular composition and involve other body systems in the pathological process. Among all acute myeloid leukemias, 5–30 % is the myelomonocytic form. The peculiarity of this form of leukemia is the extramedullary manifestations – leukemides, the appearance of which most often indicates an unfavorable prognosis. The article discusses a clinical case of acute myelomonocytic leukemia with the development of extramedullary skin lesions (leukemides) in a patient.

Background. Nowadays, hematology is a dynamically developing science due to the in-depth study of the molecular mechanisms of a particular disease. A better understanding of oncohematological diseases biology makes it possible to synthesize new targeted drugs, which have a favorable therapeutic effect. In particular, in multiple myeloma, after the introduction of proteasome inhibitors and immunomodulatory drugs into clinical practice, an improvement in overall survival was observed. However, characteristics of the mechanisms of transformation normal plasma cells into malignant ones are still difficult; therefore, the study of the pathobiological basis of multiple myeloma is currently an urgent task.
The objective: to evaluate the possible influence of MAGE-C1 gene expression and the presence of mage-c1 protein in patients with newly diagnosed multiple myeloma on the anti-tumor response after bortezomib-containing therapy.
Materials and methods. A prospective study included 33 multiple myeloma patients. The diagnosis was established according to International Myeloma Working Group criteria (IMWG, 2014). In 32 patients the induction therapy included bortezomib-containing courses, in one patient lenalidomide was included in the first-line regimens. The MAGE-C1 gene expression by real-time polymerase chain reaction and mage-c1 protein by immunohistochemistry in plasma cells bone marrow, were determined for all patients at the debut of multiple myeloma. As a control group was examined the bone marrow material of healthy donors.
Results. When assessment the statistical relationship between the expression of MAGE-C1 gene and mage-c1 protein, it was found that there was no high expression of mage-c1 protein at low values of MAGE-C1 gene expression. At the same time, high expression of the gene was always associated with protein expression above normal values. The analysis aimed at finding the relationship between MAGE-C1 gene and mage-c1 protein detection and the degree of antitumor response after 6 courses of induction therapy showed that high expression of the studied parameters was associated with a worse response to bortezomib-containing treatment.
Conclusion. We confirmed that the results of the two methods were comparable. Single factor analysis showed that patients with decreased MAGE-C1 gene and mage-c1 protein expression levels achieved a significantly higher antitumor response to bortezomib-containing regimens, while high expression was accompanied by refractoriness to bortezomib.

Background. The study of genetic predictors of non-Hodgkin’s lymphomas prognosis is one of the most relevant areas of oncohematology. It is extremely interesting to search for integral markers that reflect the most important stages of tumor pathogenesis. DNA repair system plays one of the key roles in genomic instability. Aberrations of microsatellite repeats such as microsatellite instability (MSI), in particular elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is characteristic for mismatch repair system and loss of heterozygosity (LOH) is an integral feature of genomic instability.
Objective. Analysis of MSI, EMAST, LOH significance in follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and high-grade B-cell lymphoma (HGBL) patients.
Materials and methods. The study was performed by multiplex PCR and fragment analysis with diagnostic panels COrDIS Plus and COrDIS MSI in 85 FL patients, 32 DLBCL patients, and 37 HGBL patients.
Results. The frequency of LOH in the general FL group was 40/81 (49.4 %), MSI – 10/82 (12.2 %), EMAST – 15/81 (18.5 %). The frequency of LOH in the HGBL group was 21/31 (67.8 %), MSI – 11/37 (29.7 %), EMAST – 13/31 (41.9 %). The frequency of LOH in the DLBCL group was 18/29 (62.0 %), MSI – 5/32 (15.6 %), EMAST – 14/32 (43.8 %). When considering the morphological types of FL, it was noted that a higher frequency of genetic aberrations was characteristic of lymphomas with a more aggressive morphology (p <0.05). LOH identifies FL and HGBL patients with an unfavorable prognosis. The EMAST analysis allows identifying additional patients in the LOH+ cohort with early events and low EFS.
Conclusion. LOH and EMAST have a prognostic value for FL and HGBL. No associations of LOH and EMAST with the survival were observed in DLBCL. Changes in mononucleotide repeats in FL, DLBCL and HGBL did not correspond to the MSI-H characteristic of solid tumors. For this reason, the clinical consequences of MSI-H in solid neoplasms, in particular the efficacy of immune checkpoint inhibitors, in lymphomas cannot be expected to be replicated solely on the basis of microsatellite aberrations detection.

Background. Diffuse large B cell lymphoma (DLBCL) is one of the most common non-Hodgkin’s lymphomas. The effectiveness of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone) therapy was observed in about 60 % of patients, in 20–30 % of cases DLBCL is characterized by a refractory course. Standard clinical prognostic criteria do not accurately determine the prognosis of the disease. In this regard, the problem of developing additional predictors of DLBCL course remains relevant today and is directly related to the molecular pathogenesis of the disease.
The objective: to determine the relationship of pSTAT3, pSyk with c-Myc, p53, BCL2 oncoproteins expression and survival of DLBCL patients.
Materials and methods. Biopsy specimens of lymph nodes and other organs and tissues obtained from 100 patients with newly diagnosed DLBCL were used for the study. All patients received standard first-line immunochemotherapy according to the R-CHOP regimen. Determination of the relative amount of tumor cells expressing pSTAT3, pSyk was carried out using immunohistochemical and morphometric methods. The threshold value of proteins expression was calculated using the ROC analysis: for pSTAT3 it was 68 % of positive tumor cells, for pSyk – 28 %. The relationship of pSTAT3, pSyk with c-Myc, p53, BCL2 expression was determined using the Pearson χ2  test. Overall (OS) and progression-free (PFS) survival were calculated using the Kaplan–Meier method (log-rank test).
Results. The suprathreshold pSTAT3 expression was found to be associated with a high content of c-Myc and p53 transcription factors in tumor cells (p = 0.015 and p = 0.010, respectively). In the group of patients with isolated overexpression of pSTAT3, the 5-year OS and PFS were lower, and the risk of death and disease progression was almost 1.5 times higher than in patients with low protein expression (p = 0.015 and p = 0.011, respectively). When studying the co-expression of pSTAT3 and pSyk, the lowest OS and PFS were recorded in the subjects with a simultaneous high expression of these proteins. With this combination of markers, the probability of an adverse event in patients when calculating OS increased by 2.9 times (p = 0.003; hazard ratio 2.9; 95 % confidence interval 1.43–5.85), and when analyzing PFS – by 2.3 times (p = 0.021; hazard ratio 2.3; 95 % confidence interval 1.14–4.87) compared with other variants of their simultaneous expression.
Conclusion. Overexpression of pSTAT3 is associated with unfavorable biological tumor characteristics and poor patient survival. The combined suprathreshold expression of the pSTAT3 and pSyk proteins is associated with lower OS and PFS values compared to their isolated expression.

Background. An autologous stem cell transplant (ASCT) is the standard of treatment young and fit patients with multiple myeloma (MM). The using this method of treatment is limited due to the high consumption of economic and intellectual resources, the low availability of Cryobank departments in regions of Russia.
Objective: to evaluate the efficacy and safety of using non-cryopreserved peripheral blood stem cells (non-CRYO PBSCs) in patients with multiple myeloma who underwent autologous transplantation.
Materials and methods. We conducted a prospective study of the efficacy and safety of using non-CRYO PBSCs in patients with MM who underwent ASCT. The number of PBSCs apheresis procedures in 82.9 % (n = 29 pts) was 1 day, and in 17.1 % (n = 6 pts) was 2 days. After apheresis, PBSCs were stored at a temperature of +4…+6 °C in a blood bank refrigerator for up to 72 hours. During 4 years, ASCT using non-CRYO PBSCs was performed in 35 patients with MM. The average number CD34+  cell dose was 2.63 × 106 /kg. The median time to neutrophil engraftment was 11 days (range from 9 to 14). The median time to platelet engraftment was 12 days (range from 8 to 19). The control group included 43 patients with MM, who underwent PBSCs ASCT according to the traditional method, including preparation and cryopreservation of the apheresis product of PBSCs with cryoprotectant dimethyl sulfoxide, as well as subsequent defrosting on the day of transplantation (day 0).
Results. There were no significant differences comparing the safety of ASCT in non-CRYO and CRYO PBSCs groups among such parameters as the viability of PBSCs, the frequency of complications, the time of hematopoietic engraftment, the need for platelet and red blood cells transfusion therapy, and time of hospitalization.
Conclusion. Hence, the method of short-term storaging non-CRYO PBSCs is not inferior to the traditional method of controlled freezing, is more economical and can be used in medical organizations that do not have a Cryobank in their structure.

Monoclonal anti-CD20 antibodies in lymphomas therapy during the COVID-19 pandemic: pro and contraThe review presents the results of a combined analysis of literature data and own clinical observations regarding the safety and feasibility of using monoclonal anti-CD20 antibodies in the treatment of B-cell lymphoproliferative diseases during the COVID-19 pandemic. The main points of the pathogenesis of the influence of monoclonal anti-CD20 antibodies on the course of COVID-19 are described. The current trends in the modification of the accepted algorithms of lymphoproliferative diseases therapy with the inclusion of monoclonal anti-CD20 antibodies are summarized, and the possibilities of specific prevention by vaccination against COVID-19 are also considered.

In the era of COVID-19, the chemotherapy of patients with hematological malignancies has become the cornerstone in hematology. Secondary immunodeficiency as a result of hemoblastosis, predisposes to a more severe course of coronavirus infection, and specific antitumor treatment only exacerbates patients immunodeficiency. Thus, there is a problem of conducting chemotherapy during the COVID-19 pandemic. At the moment, there are no unified recommendations for risk assessment and choice of treatment for patients with oncohematological diseases and concomitant coronavirus infection. In this article, we present a series of clinical cases of patients with hematological malignancies diagnosed with coronavirus infection at the onset of a hematological disease or after chemotherapy. Patients with long-term persistent coronavirus infection requiring specific anticancer treatment were allocated to a separate group. We hope that this article will help to set a vector for further research, as well as serve as a clear example of the clinical situations that a hematologist may face during the COVID-19 pandemic.

Invasive fungal infections in various categories of patients remain one of the most urgent problems of modern medicine. This is complicated by the imperfection of diagnostic methods, as well as a small range of antimycotics for systemic use. The market launch in 2005 of posaconazole, a second-generation systemic antimycotic from the group of triazoles with a wide spectrum of activity in the form of an oral suspension, was an event in medical mycology. However, pharmacokinetic features of suspension have caused certain problems with its use. The suspension was replaced by a tablet form, largely devoid of these shortcomings, and then a solution for intravenous administration, which was registered in Russia at the end of 2021 (significantly later than in other countries of the world). Registration of an intravenous form of the drug with the possibility of using both for a stepdown approach and in patients who, for different reasons, cannot take posaconazole orally, had a positive impact on the problem of choosing antimycotics for the prophylaxis and treatment of invasive fungal infections. In this article, we will consider the features of the clinical pharmacology of the intravenous form and its place in the prophylaxis and treatment of invasive mycoses.

The incidence of malignant lymphomas has been increasing in recent years worldwide. These diseases are often accompanied by venous thromboembolic complications (VTEC). The development of VTEC leads to interrupting of therapy, increasing mortality and significant rising of treatment costs. Anticoagulants are effective in VTEC prophylaxis. Prescribing of anticoagulant therapy is based on VTEC different risk scales, which are far from perfect. The search of additional features for hemostasis assessment can increase the prognostic value of these scales. The optimization of VTEC risk scales can improve efficacy of anticoagulant therapy and decrease an incidence of thrombotic events in patient with malignant lymphomas. The article presents a literature review and own clinical observations regarding the VTEC risk assessment in patients with lymphoproliferative diseases.

Proteasome inhibitors and immunomodulators (IMiDs), primarily bortezomib and lenalidomide, are essential components of treatment for both newly diagnosed and relapsed/refractory multiple myeloma (MM), producing high response rates and resulting in improved overall survival. However, bortezomib often induces a dose-limiting toxicity in the form of peripheral neuropathy (PN). Neurotoxicity often affects patient’s quality of life and requires dose modification or withdrawal of therapy, with a possible effect on the overall response. A prompt recognition of predisposing factors (such as diabetes mellitus, vitamin B₁₂ deficiencies, or viral infections) and appearance of signs and symptoms, through a periodic neurological assessment with appropriate scales, is extremely important. Usually, bortezomib-induced PN is a sensory axonopathy characterized by numbness, tingling, and severe neuropathic pain in stocking and glove distribution while motor neuropathy is less frequently observed. Dose adjustment of bortezomib could be necessary during treatment. Anticonvulsants (pregabalin, gabapentin, carbamazepine, etc.) and tricyclic antidepressants (amitriptyline) are most often used to relieve neurological pain. In this review we focus on the clinical manifestations of bortezomibinduced PN, current understanding of the pathophysiological mechanisms as well as clinical and pharmacological aspects of prevention and management this complication. New proteasome inhibitors such as ixazomib and carfilzomib do not have the neurotoxicity of bortezomib. An early switch within the class of proteasome inhibitors from bortezomib to oral ixazomib appears to be an important approach to prevent severe PN. Our own clinical case of an early switch from bortezomib-based induction to IRd triplet (ixazomib, lenalidomide, dexamethasone) is cited as an illustration of the success of this approach.