Introduction. Before the introduction of targeted agents, multiple myeloma (MM) was characterized by low overall survival (OS) rates. Survival during the first year of life is a clear indicator of the effectiveness of not only antitumor therapy but also accompanying therapy. Analysis of the cause of death in the MM patient population will allow for refined approaches to diagnosis, antitumor treatment, and accompanying therapy.

Aim: to determine the one-year OS rates in patients with newly diagnosed MM, to study the cause of death, and to estimate the probability of death within the first year after diagnosis.

Materials and Methods. This multicenter prospective study, conducted from January 2015 to October 2018, included 3,184 patients (1,339 men and 1,845 women) with newly diagnosed MM from 40 regions of Russia, aged 24–90 years. One-year OS, one-year mortality, and causes of death were analyzed.

Results. During the follow-up period, 2,307 deaths were recorded, 261 patients were lost to follow-up, and 616 patients continue to receive antitumor therapy or remain untreated. The median OS of patients with MM was 44 months, with a 5-year OS probability of 40 % and a 10-year OS probability of 17 %. Among 2,307 patients with documented fatal outcomes, causes of death were available in 1,350 cases. In 55.7 % (n = 752) of cases, death was determined to be due to MM progression, in 19 % (n = 257) to infectious complications, in 8.2 % (n = 111) to acute cardiovascular failure, and in 4 % (n = 54) to acute kidney injury. Pulmonary embolism was documented in 3.6 % of patients (n = 49), and mesenteric vascular thrombosis was diagnosed in 0.3 % (n = 4) of cases. Acute cerebrovascular accident, both ischemic and hemorrhagic, was diagnosed in 3.7 % (n = 50) of cases resulting in death. A second malignancy was the primary cause of death in 1.6 % (n = 22) of patients with MM. The one-year OS rate for patients newly diagnosed with myeloma from 2015 to 2018 was 82 %. The 5-year probability of death from myeloma progression was 31 %, while the 1-year probability was 9 %. Meanwhile, the 5-year probability of death from causes unrelated to myeloma progression was 45 %, while the 1-year probability was 11 %.

Conclusion. The probability of death from causes unrelated to refractory myeloma was comparable across all age cohorts. This highlights the need for knowledge regarding concomitant therapy and the correction of comorbid factors. Differences in the one-year OS of patients with myeloma were demonstrated depending on the registration center, due to differences in access to second- and subsequent-line anticancer drugs. It is important to note the need to develop a separate treatment strategy for the cohort of patients with myeloma diagnosed in old age.

Introduction. Therapy with Bruton tyrosine kinase inhibitors is associated with an increased risk of cardiovascular complications including atrial fibrillation and arterial hypertension and elevated risk of bleeding events. However, there is still little data regarding both the real-world frequency and phenotypic presentation of cardiovascular complications during BTK inhibitor therapy, as well as the long-term prognosis of patients experiencing these events.

Aim. To compare the incidence of cardiovascular complications and hemorrhagic events, and to evaluate their prognostic significance in patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib versus acalabrutinib.

Materials and Methods. This retrospective study included 710 patients with CLL: 605 patients received ibrutinib, 69 received acalabrutinib and 36 received ibrutinib and were subsequently switched to acalabrutinib for various reasons. A comparative analysis was performed between the groups of patients treated with either ibrutinib or acalabrutinib. To eliminate the influence of age and sex as major risk factors for cardiovascular complications, a matching-adjusted indirect comparison (MAIC) was conducted, with patients in the groups matched for age and sex. The primary endpoint of the study was atrial fibrillation (AF). Additionally, the following events were recorded: decompensated heart failure (HF), arterial hypertension (AH) and bleeding. To evaluate outcomes, a composite endpoint of prognostic events was used, comprising thrombotic complications, clinically significant bleeding, and cardiovascular death. The incidence of AF, AH and HF was assessed among surviving patients.

Results. Acalabrutinib was associated with an eightfold reduction in the risk of new-onset AF (22 % for ibrutinib vs. 3.4 % for acalabrutinib; OR 0.12; 95 % CI: 0.02–0.54; р = 0.006). The incidence of AH and HF was comparable between the two drugs. Comparative analysis revealed a five-fold reduction in the risk of prognostic events in patients receiving acalabrutinib (RR 0.214; 95 % CI: 0.051–0.907; р = 0.036). When evaluating the structure of prognostic events, the differences between groups were driven by a higher incidence of thrombotic complications: ischemic stroke (10 % with ibrutinib vs. 1.5 % with acalabrutinib; p = 0.033) and venous thrombosis (15 % with ibrutinib vs. 6 % with acalabrutinib; р = 0.061), while the incidence of bleeding remained comparable.

Conclusion. Patients receiving acalabrutinib exhibited an eight-fold reduction in the risk of developing AF. When assessing the long-term prognosis, acalabrutinib therapy was associated with a five-fold decrease in the risk of prognostic events due to a lower incidence of thrombotic complications, while the frequency of bleeding remained comparable.

Introduction. The study of the genetic characteristics of donors from regions of the Russian Federation is necessary to determine the frequency of occurrence of HLA alleles and haplotypes of donors and the level of recruitment activity. The study of the immunogenetic characteristics of donors recruited in various regions of the country is an urgent area of research.

Aim: to evaluate the immunogenetic characteristics of bone marrow and hematopoietic stem cell donors residing in St. Petersburg.

Materials and Methods. Blood samples were obtained from 691 donor-residents of St. Petersburg in the period from January 2024 to August 2024. Genomic DNA was isolated from 200 μl of peripheral blood with EDTA by column filtration. The concentration and quality of DNA preparations were measured using spectrophotometry, samples with concentrations from 5 to 100 ng/ml were taken into the study, and, if necessary, DNA samples were normalized with deionized water. HLA typing was performed using NGS technology in 2-field resolution at the HLA-A, HLA-C, HLA-B, HLA-DRB1 and HLA-DQB1 loci by mass parallel sequencing. The data was analyzed using the software in an automatic mode. To determine the frequencies of HLA alleles and haplotypes, the maximum likelihood method was used using the EM algorithm for poly-locus data.

Results. The study identified 36 allelic variants of the HLA-A, 32 HLA-C, 58 HLA-B, 37 HLA-DRB1, 20 HLADQB1 locus. Five-locus HLA haplotypes were established. The obtained results were compared with data from Russian donor populations. The study determined the frequency of occurrence of HLA -alleles and five-locus haplotypes in donors from St. Petersburg.

Conclusion. The presence of a significant number of alleles of each gene and the number of alleles detected once in a relatively small sample was revealed, which indicates a high immunogenetic diversity of donors-residents of St. Petersburg. Further research should be directed towards expanding the pool of donors typed in high resolution, which will increase the chances of selecting a compatible donor.

Introduction. Dual antiplatelet therapy (DATT) with aspirin and a platelet P2Y12 receptor inhibitor is one of the main components of treatment and secondary prevention in patients undergoing percutaneous coronary intervention in acute myocardial infarction. Among the side effects of DATT are hemorrhagic complications caused by the antiplatelet effect of the drugs. Less is known about hemorrhagic complications caused by coagulation disorders when taking clopidogrel.

Aim: to present a clinical case of acquired hemophilia A, which occurred in a patient as a result of taking clopidogrel.

Main findings. A 68-year-old patient received clopidogrel as part of DATT after percutaneous coronary intervention. One month later, he developed a pronounced hemorrhagic syndrome caused by the appearance of antibodies to coagulation factor VIII (FVIII:C 1.5 %, factor VIII inhibitor 61 BU). The elimination of clopidogrel, hemostatic therapy with eptacog alpha (activated) and immunosuppressive therapy with prednisone, cyclophosphamide and rituximab allowed not only to stop the hemorrhagic syndrome, but also to achieve eradication of the inhibitor.

Chronic graft-versus-host disease (cGVHD) is one of the most significant late complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). First-line therapy is based on glucocorticosteroids; however, a substantial proportion of patients develop steroid-refractory disease requiring subsequent lines of treatment. In recent years, targeted therapies have been introduced into clinical practice, including belumosudil, a selective ROCK2 inhibitor.

Aim: to evaluate the efficacy and safety of belumosudil in patients with severe steroid-refractory cGVHD.

Main findings. In the presented case series, patients with severe cGVHD with lung involvement, refractory to glucocorticosteroids and prior therapies (including JAK inhibitors, antifibrotic, and immunomodulatory agents), received belumosudil as thirdor later-line treatment. Partial response was achieved in one patient, while disease stabilization was observed in two patients. In all cases, the treatment demonstrated a favorable safety profile, with no serious adverse events requiring discontinuation. These findings suggest that belumosudil is clinically effective in heavily pretreated patients, including those with advanced pulmonary involvement. However, the limited reversibility of fibrotic changes supports the rationale for earlier initiation of therapy.

Introduction. Primary vitreoretinal lymphoma (PVRL) is a subtype of lymphoma of immune-privileged organs. Both diagnosis and treatment decisions pose significant challenges for PVRL.

Aim: to present a clinical observation in treating patients with PVRL and possibilities for improving diagnosis and treatment outcomes.

Main Findings. Since 2024, two patients with PVRL, aged 66 and 75 years, have been treated at the National Medical Research Center for Hematology. Modern diagnostic methods based on molecular analysis to detect mutations in the MYD88/ CD79b genes in vitreous fluid were used to establish the diagnosis. A two-stage approach was used for treatment: remission induction using the R-MPV protocol with the addition of lenalidomide and ibrutinib, followed by consolidation auto-HCT in a conditioning regimen according to the “BBC” program. Disease relapses were detected in both patients early after auto-HCT. Thus, for timely diagnosis, it is advisable to implement minimally invasive methods for studying the molecular profile of PVRL. The development of new therapeutic approaches, integrating innovative cell therapy into first-line treatment and the use of thiotepa-based conditioning regimens, is also advisable.

Introduction. Classical Hodgkin lymphoma (cHL) is predominantly diagnosed in women of reproductive age. The expanding use of PD-1 inhibitors in the treatment of cHL increases the likelihood of pregnancy being detected during immunotherapy. However, only a limited number of such observations have been described in the literature, which complicates the choice of an optimal management strategy for these patients.

Aim: to present two clinical case reports of patients with cHL: in the first, the beginning of pregnancy (4 weeks) occurred during nivolumab exposure; in the other patient, nivolumab was administered during the periconceptional period, 6 weeks before conception.

Main Findings. In the first case, pregnancy was diagnosed at 6 weeks of gestation during maintenance therapy with nivolumab 40 mg every 2 weeks (cumulative dose 600 mg); the last dose was administered at 4 weeks of gestation, and treatment was discontinued after pregnancy was confirmed. Spontaneous delivery occurred at 38 weeks: a boy, birth weight 2910 g, length 49 cm, Apgar scores 8 and 9. In the second case, pregnancy was diagnosed at 3 weeks of gestation after completion of the Nivo-DHAP course with nivolumab at a dose of 240 mg. After pregnancy was confirmed, antitumor treatment was discontinued. Delivery at 38 weeks: cesarean section, a girl, birth weight 3000 g, length 52 cm, Apgar scores 8 and 9. The presented clinical case reports add to the limited clinical data on the course of pregnancy during the use of PD-1 inhibitors and highlight the need for multidisciplinary management and individualized decision-making, taking into account the potential risks to the mother and the fetus.

Introduction. Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare childhood cancer predisposition syndrome.

Aim: to present a unique clinical case of a patient with relapsed T-lymphoblastic lymphoma who was diagnosed with a rare hereditary cancer predisposition syndrome (constitutional mismatch repair deficiency syndrome).

Main findings. The cause of CMMRD is considered to be the presence of biallelic germline homo- or compound-heterozygous variants in one of the four MMR genes ( MLH1, MSH2, MSH6 or PMS2 ); inactivation of these genes leads to an increased mutational burden and, consequently, to malignant transformation of cells. Loss of MMR system function underlies the development of a broad spectrum of malignancies in children and adolescents, with the first neoplasm often presenting as a hematological malignancy. The long-term prognosis for patients with CMMRD remains extremely poor due to the high risk of developing metachronous malignancies of other localizations, which necessitates systematic surveillance of this patient group.

Introduction. Megakaryocytes, in addition to their function of producing platelets and maintaining their quantitative composition in the bloodstream, are a strong immune trigger. The release of these cells from the bone marrow into the peripheral blood occurs under certain conditions, both physiological and pathological.

Aim: to present a case of detecting fragments of megakaryocyte cytoplasm in an elderly patient with ischemic stroke during microscopy of a peripheral blood smear.

Main findings. When conducting a clinical blood test on an elderly patient with an ischemic stroke, a hematological analyzer revealed significant thrombocytopenia, which had not been previously observed. The number of platelets was determined using the optical method, but the platelet aggregation flag remained (100 %). Morphological examination of blood under a microscope revealed fragments of megakaryocyte cytoplasm arranged in clusters in the brush preparations, and the number of platelets corresponded to the analysis data. Upon repeated blood sampling, the number of platelets remained normal. Microscopic examination of the blood revealed platelets in the form of clusters and individual forms. Thus, when platelets are consumed excessively in certain pathologies, fragments of megakaryocytes are released into the circulation, where they “mature”. Within a few hours, the demarcation membrane formed in megakaryocytes divides the cytoplasm into numerous mature platelet plates. In order to predict the progression of thrombocytopenia and exclude early heparin-induced thrombocytopenia, it is necessary to select blood samples for clinical analysis based on specific criteria.

Introduction. Thrombocytopenia can be primary or secondary and warrants differential diagnosis of hereditary functional platelet defects.

Aim: to present the difficulties of verifying the diagnosis in disorders of the platelet component of hemostasis.

Main findings. A clinical case of a 28-year old female patient is presented. The patient presented with a mild mucocutaneous hemorrhagic syndrome and moderate thrombocytopenia of a familial nature. All available routine and alternative methods for investigating platelet disorders were performed. Whole genome sequencing proved to be a crucial diagnostic method. This genetic analysis, in comparison with morphological and functional studies, is a promising tool for the differential diagnosis of heterogeneous platelet disorders.