Introduction. The introduction of chimeric antigen receptor (CAR) T-cell therapy is a promising treatment of patients with relapsed or refractory (R/R) B-cell lymphoproliferative diseases (LPDs).

Aim — to present the results of CAR-T-cell therapy of 6 adult patients with B-cell LPDs.

Materials and methods. This is a pilot study conducted in adult patients with R/R or persistent minimal residual disease B-cell LPDs treated with CAR-T-cells. The study was approved by a local ethical committee of National Research Center for Hematology. Patients did not have alternative options for effective and safe treatment. All patients signed an informed consent. All patients were lymphodeplated with fl udarabine and cyclophosphamide for 4 days before the introduction of CAR-T-lymphocytes. Cytokine release syndrome (CRS) was prevented by tocilizumab on the day of CAR-T-cell administration. The effi cacy and safety of CAR-T-cell therapy was evaluated.

Results. From 01.01.2020 to 01.01.2022, 10 CAR-T-cell infusions were performed for 6 adult patients (age 19–68 years, median — 32 years) with B-cell LPDs: 4 — R/R B-acute lymphoblastic leukemia, 1 — R/R diffuse large B-cell lymphoma, 1 — persistence of MRD in mantle cell lymphoma. In all patients with a R/R, median — 4 (2–5) lines of chemotherapy and/ or immunotherapy were performed before CAR-T-cell therapy. CD19 CAR-T-cells received 3 patients, CD19/CD22 CAR-Tcells — 2 patients, CD19 and CD20 CAR-T-cells received 1 patient. Autologous CAR-T-cells received 4 (66 %) patients, allogeneic CAR-T-cells received 1 patient, and one patient had two CAR-T-cell administrations — 1 autologous and 1 allogeneic. The median number of CAR-T-cells was 0.5 × 10⁶ /kg (from 0.1 × 10⁶ /kg to 3 × 10⁶ /kg). In 7 (87.5 %) of the 8 cases after CAR-T-cell administration, overall response to therapy (complete or partial remission) was achieved, and complete remission was achieved in 6 (75 %) cases. Side effects were noted after 8 of 10 CAR-T-cell transfusions: CRS in 40 % (CRS 1 — 10 %, CRS 2 — 20 %, CRS 3 — 10 %), ICANS in 10 %, tumor lysis syndrome in 20 %, multi-organ dysfunction syndrome in 10 %.  There were no lethal complications due to CAR-T-cell administrations. The median follow-up period was 6 (1–16) months. Of the 6 patients, 2 (33 %) died from relapses and progression of LPD. One (17 %) patient died in complete remission from infectious complications. Three (50 %) patients are observed till now. The median time of CAR-T-cell circulation was 33 (6– 60) days.

Conclusion. CAR-T-cell therapy is a promising treatment for R/R B-cell LPDs and LPDs with persistence of MRD after cytoreductive therapy. This type of therapy requires a multidisciplinary approach.

Introduction. The use of thrombopoietin receptor agonists, especially eltrombopag, in the treatment of aplastic anemia (AA) patients who did not respond to the previous immunosuppressive therapy (IST), is accompanied by the development of a hematological response in 40–60 % of patients.

Aim — to study the effi cacy of using eltrombopag in treatment programs for AA patients refractory to previous IST.

Methods. The study included 20  AA patients who were treated at the National Research Center for Hematology from 2015 to 2020. These patients did not respond to the conducted IST (ATG + CsA). Eltrombopag was administered at a dose of 150 mg/day. The results of treatment were assessed at 3 and 6 months: the achievement of hematological improvement, partial and complete remission, as well as the identifi cation of possible clonal evolution were determined.

Results. Eleven out of 20 (55 %) patients responded to treatment: 2 patients developed hematological improvement, 6 patients — partial remission, 3 patients — complete remission. All 11 patients responded to treatment within 12 months from the start of eltrombopag, but further positive dynamics of hematological parameters are possible. The median duration of treatment with eltrombopag was 11 (1–48) months. Most of the patients were treated with eltrombopag in combination with CsA. The duration of the course of treatment with eltrombopag depended on the response received (stable hematological improvement, remission, as well as the detection of clonal evolution) or its absence and the need for ATG or BMT. An aberrant karyotype was found in 2 AA patients who received eltrombopag: in one patient monosomy of chromosome 7 was detected 1 month after the start of treatment, in another patient, 37 months later, a clone with a derivative of chromosome 16 from t(1;16) and subclone with complex disorders of the karyotype without signs of myelodysplasia in the bone marrow.

Conclusion. The inclusion of the TPO receptor agonist eltrombopag in the treatment program for AA patients allows for a stable hematological response and remission of AA for patients who have not responded to IST. The effectiveness of eltrombopag is determined by adherence to the treatment algorithm, the optimal duration of the course, and the dose of the drug used. There is still a need for long-term observation of the patient and control morphological and cytogenetic studies.

Introduction. Pregnancy is one of the most frequent triggers of congenital and acquired forms of thrombotic thrombocytopenic purpura (TTP).

Aim — to develop tactics for the treatment of pregnant women with TTP.

Results. TTP was associated with pregnancy in 55.5 % of all cases of TTP in women. In 5 pregnancies in which the diagnosis of TTP was known before pregnancy, or established in the early stages, TTP was treated throughout the pregnancy. In the congenital form, plasma transfusions were performed once every two weeks until the  20th  week of pregnancy, or  weekly, if thrombocytopenia < 150 × 10⁹ /L persisted. Plasma transfusions were performed weekly after the 20th week with the goal of achieving clinical remission. With acquired TTP, glucocorticosteroids and plasma exchanges were used as  treatment, in 1 case — rituximab, with the aim of achieving a clinical remission and an ADAMTS13 activity > 20 %. In this group of pregnant women, 1 caesarean section was performed and there were 4 cases of vaginal deliveries, with a total of 5 children being born with an average Apgar score of 7.5. In 7 pregnancies in which TTP fi rst manifested late, leading to a delayed diagnosis, preventive and curative measures were not carried out before delivery. In this group there were 2 abortions of pregnancy, 5 surgical deliveries, 3 cases of preeclampsia, 3 acute cerebral circulatory disorders, 1 intraabdominal bleeding, 1 case of acute renal failure, with two women undergoing mechanical ventilation. There was 1 case of antenatal fetal death, with a total of 4 children being born, who were assessed on the Apgar scale with an average of 5 points.

Conclusion. Timely diagnosis as well as ongoing therapeutic and preventive measures help to avoid complications during childbirth in pregnant women with TTP.

Introduction. Oxidative stress is one of the important causes of red blood cells (RBCs) storage lesion. As a hormone, melatonin (MT) is also an effective antioxidant, however the pro- and antioxidative properties of MT depend on the cell type, redox state, as well as experimental conditions.

Aim of this study — to investigate the protective effects of low concentration of MT on the stored RBCs in vitro.

Materials and methods. Leukofi ltered RBCs were incubated in MAP RBC additive solution with or without 150 pg/mL of MT for 42 days under blood bank conditions. The morphology, aggregation index, methemoglobin (MetHb), m alondialdehyde (MDA), glucose, lactic acid and ATP of RBCs were detected on days 0, 7, 14, 21, 28, 35 and 42 to observe the protective effects of MT during the storage of RBCs.

Results. During RBCs s torage, the number of deformed RBCs, relative hemolysis rate, aggregation index, MDA and MetHb were signifi cantly affected by both storage time (p  <  0.0001) and melatonin (p  <  0.01), and they had interaction only on the number of deformed RBCs (p < 0.0001). The concentration of glucose, lactic acid and ATP were affected by storage time (p < 0.0001), but not by MT concentration (p > 0.05). The number of deformed RBCs, relative hemolysis rate, MDA and MetHb in MT group were signifi cantly lower than that in control group at the end of storage stage (p < 0.05).

Conclusion. Our study showed low hypnotic drug concentration of MT is speculated to have protective effects on the quality of stored RBCs through antioxidative mechanism. 

Introduction. 13q14 deletion is the most common chromosomal abnormality in chronic lymphocytic leukemia (CLL), and as the sole abnormality determines the most favorable prognosis of the disease. Using molecular genetic methods two subtypes of 13q14 deletion were identifi ed based on the size of the lost chromosomal material: small (type I) with the involvement of the D13S319 segment containing MIR15A/MIR16-1 and DLEU1 genes and large (type II) containing centromeric region of 13q14 involving RB1 gene. Data on the impact of type I and II deletions on the course of CLL are controversial.

Aim — to evaluate the prognostic signifi cance of different variants of 13q14 deletion in CLL.

Patients and methods. The study enrolled two cohorts of CLL patients. Cohort 1: 256 patients who were studied by FISH with DNA probes for detection of 13q14/D13S319, 11q23/ATM, 17p13/TP53 deletions, and trisomy 12 before immunochemotherapy. 101 patients with identifi ed 13q14/D13S319 deletion were analyzed with a DNA probe for RB1 locus for determination of deletion size (type I or type II). Cohort 2: 28 patients at different stages of the disease with deletion 13q14 detected by FISH were studied by using combination of standard and molecular cytogenetic methods (mFISH, mBAND, arrayCGH) to clarify the structure of 13q abnormalities.

Results. In Cohort 1 chromosomal aberrations were detected in 75 % of patients: 13q deletion — 52 % (isolated — 36 % of all cases and 48 % of cases with deletion), 11q deletion — 19 %, +12 — 13 %, 17p deletion — 6 %. 13q14 deletion type I was detected in 56 %, type II — in 44 % of patients. Type II deletion correlated with the presence of 11q deletion (p = 0.05). Isolated deletions of type I and II were found in 61 and 39 %, respectively. Biallelic deletion was identifi ed in 12.7 % of patients with 13q deletion. Statistically signifi cant differences in OS were obtained in type I and II groups of patients with isolated 13q14 deletions: median OS was not reached and made 67.5 months, respectively, p = 0.05. In Cohort 2 structural abnormalities of chromosome 13 by conventional cytogenetic analysis (CCA) were identifi ed in 50 % of cases: 13q deletion — 11 cases; translocations involving 13q14 — 6 cases. In 5 cases with biallelic deletion identifi ed by FISH, 13q14 deletion by CCA was detected in two patients, and only in one allele.

Conclusion. In general, 13q14 deletion is a cytogenetic factor of favorable prognosis for CLL but its structure is heterogeneous. Loss of tumor suppressor RB1 (type II deletion) negatively affects OS in patients treated with immunochemotherapy

Introduction. Infections are among the most common complications after allogeneic hematopoietic stem cell transplantation.

Aim — to provide a literature review on the main characteristics of infectious complications after allogenic hematopoietic stem cell transplantation and risk factors for their development.

Main findings. Apart from direct factors such as neutropenia, hypogammaglobulinemia, and lymphopenia, there are indirect transplant-related factors such as conditioning regimen, transplant source, donor type, and graft-versus-host disease prophylaxis associated with higher infectious risk posttransplant. This review also presents the main characteristics of infections after allogeneic hematopoietic stem cell transplantation with a focus on bloodstream infections and provides an overview of the main transplant-related risk factors linked to their development. 

Introduction. The study of minimal residual disease (MRD) has become an integral part of various treatment protocols for acute leukemia. Methods of polymerase chain reaction (PCR) and multicolor fl ow cytometry (MFC) are most widely used to assess MRD.

Aim — to characterize the main technologies for the detection of residual tumor cells in acute leukemia

Main findings. Various approaches for detecting MRD are described: PCR with patient-specifi c primers for rearranged genes of immunoglobulin and/or T-cell receptors, reverse transcription PCR for detecting chimeric transcripts and assessing the expression of overexpressed genes, as well as the basics of detecting MRD by MFC. Each of these approaches has its own advantages, disadvantages, and limitations of use.

Introduction. Polysaccharides, glycoproteins and glycolipids, which determine the group-specifi c properties of human blood, are both structural elements of the whole organism and determine its predisposition to certain somatic and infectious diseases. Thus, the blood group of an individual can be used among other markers and/or prognostic factors of the occurrence and course of certain groups of diseases.

Aim — analysis of literature sources characterizing the relationship of blood groups with COVID-19 ARVI, as well as the mechanisms underlying this relationship.

Main findings. The O_aß(I) phenotype ensures an individual’s resistance to infection with the SARS-CoV-2 virus and allows for a relatively mild course of the disease. The A_ß (II) phenotype is a risk factor for the development of COVID-19 ARVI, in its severe course, the occurrence of complications and increased mortality. An additional component of protection in the form of a negative Rh-affi liation of the infected person is not excluded. The protective properties of the O_aß(I) phenotype are associated with the absence of polysaccharide A in an individual and the presence of anti-A antibodies. The increased risk of COVID-19 ARVI among A_ß (II) individuals is due to the large polymorphism of polysaccharide A in the environment and the lack of natural immunity to other forms of polysaccharide A in this group.

Introduction. Hemophilic arthropathy and the subsequent development of osteoarthritis in the large foot joints often require surgical intervention. At the same time, the course of hemophilia and the need to correct blood clotting factors make it diffi cult to manage the patient. The lack of awareness of the operating surgeon can serve as a reason for refusing the operation.

Aim — to present a clinical case of hemophilic arthropathy of the subtalar joint in a patient with hemophilia B who underwent fusion.

Main findings. The observation demonstrates the complexity of perioperative management and the need for the selection and correction of individual factor replacement therapy. A clinical case may be of interest to trauma surgeons, orthopedists, as well as clinical pharmacologists working in surgical hospitals.

Introduction. The development of febrile neutropenia complicates the course of the post-chemotherapeutic period in many patients with acute leukemia. Febrile neutropenia — the most common complication of the post-chemotherapeutic period in patients with acute leukemia (AL), and the concomitant infectious complications can cause life-threatening conditions. Invasive fungal infections in AL patients during neutropenia can be extremely severe.

Aim — to present a clinical observation and successful diagnosis and treatment of the rare fungal infection induced by fungi of the genus Fusarium in an immunocompromised patient.

Main findings. A clinical observation, diagnosis and treatment of a rare fungal infection caused by the fungi of the Fusarium genus is presented. The taxonomic variety of Fusarium is given, and the morphological and molecular methods of diagnostics are highlighted. Special attention is given to the choice of appropriate antifungal therapy of fusariosis.