AIM. To assess the therapy outcomes in pediatric patients with acute myeloid leukemias (AMLs) as well as to identify the most important poor prognostic factors and predictors of treatment efficacy. MATERIALS & METHODS. The retrospective analysis includes 35 newly diagnosed AML patients treated at the Moscow Regional Oncology Dispensary from 2018 to 2025. On diagnosis date, the age range was 0 to 17 years (median 7 years). Therapy (standardized induction and consolidation blocks, targeted drugs if needed, and allogeneic hematopoietic stem cell transplantation [allo-HSCT] in first remission) was administered in accordance with risk groups and obligatory monitoring of minimal residual disease (MRD). Clinical and laboratory features, cytogenetic and molecular markers (FLT3-ITD, NPM1, and CEBPA) as well as MRD were assessed after 1–2 courses of induction therapy. The distribution of FAB types was as follows: M7 in 6 (17.1 %), M1 in 5 (14.3 %), M4 in 5 (14.3 %), M5 in 4 (11.4 %), M5a in 4 (11.4 %), and M2 in 4 (11.4 %) cases; other types were detected in 7 (20 %) cases in total. Risk stratification identified 20 (57.1 %) high-, 12 (34.3 %) intermediate-, and 3 (8.6 %) standard-risk patients. RESULTS. At the time of this publication, 21 (60 %) patients are alive, and 14 (40 %) patients have died. The 3-year overall survival was 60 %, and event-free survival (EFS) was 41 %. In the studied cohort of AML patients, early MRD-negative status appeared to be the main predictor of favorable outcome: with MRD ≥ 0.1 % as early as after the first control examination (25.7 % of patients), the number of events significantly increased and long-term rates decreased, whereas achieving MRD-negative status at the end points went hand in hand with the formation of a pronounced plateau on the EFS curve. Clinical and cytogenetic high-risk parameters (FLT3-ITD mutation, hyperleukocytosis at the start, and extramedullary lesions) were associated with earlier unfavorable outcomes and required treatment escalation. The strategy of incorporating allo-HSCT into first-line therapy proved to have outstanding clinical efficacy for high-risk patients and those with MRD persistence. CONCLUSION. The results obtained are consistent with multi-center data on pediatric protocols of AML treatment. This study demonstrated that the risk-adapted therapy taking into account molecular genetic features of the tumor clone as well as MRD monitoring with the routing of patients to allo-HSCT if needed in first complete remission improve long-term survival rates in pediatric AML patients.
Sclerosing angiomatoid nodular transformation (SANT) is a rare benign non-neoplastic vascular disease of the spleen which is characterized by multiple angiomatoid nodes separated by fibrous stroma. In most cases, SANT is asymptomatic and usually comes to light as an incidental finding on an ultrasound scan. T-cell clone of uncertain significance (T-CUS) and reactive cytotoxic Т-cell population may be induced by virus infections, autoimmune diseases, or tumors. These disorders require differential diagnosis with large granular lymphocyte (T- or NK-cell) leukemia which in 1/3 of patients is marked by asymptomatic cytopenia on diagnosis date. This paper reviews the literature and is the first to describe the combination of several pathologic events including SANT of the spleen and reactive cytotoxic Т-cell population, identified during the examination for the tumor of the right kidney with aggressive fatal course.
BACKGROUND. The etiology of plasmacytomas in multiple myeloma (MM) remains unclear, whereas the pathogenetic mechanisms of extramedullary lesions are of particular importance because of extremely poor prognosis. The incidence of bone and extramedullary plasmacytomas complicating the course of MM as well as the efficacy of therapy for this disease are still underresearched. AIM. To assess the incidence of bone and extramedullary plasmacytomas in patients with newly diagnosed MM (ndMM) and analyze the overall survival (OS) rates depending on whether soft-tissue components were detected. MATERIALS & METHODS. This multi-center prospective study enrolled 3184 ndMM patients (1339 men and 1845 women) from 40 regions of Russia, aged 24–90 years and treated during the period from January 2015 to October 2018. The electronic patient records included demographic, clinical, laboratory, and instrumental documentation data accessible on MM diagnosis date. Bortezomib-based regimens were administered in the first-line therapy to 94 % of patients. RESULTS. Bone and extramedullary plasmacytomas were diagnosed in 763 (24 %) out of 3184 ndMM patients. At disease onset, the median hemoglobin concentration was significantly higher in patients with bone (105 g/L) and extramedullary (102 g/L) plasmacytomas than in patients without them (95 g/L; p < 0.05). The median percentage of plasma cells in the bone marrow was significantly lower in cases of bone plasmacytoma accounting for 25 % vs. 30 % in cases of extramedullary components, and it was 31 % in patients without plasmacytomas at MM onset (p < 0.05). Most commonly, plasmacytomas were detected in the thoracic spine (24.3 %; n = 132) and ribs (13.6 %; n = 74). The median OS of patients without plasmacytomas was 46 months (95% confidence interval [95% CI] 43–49 months) vs. 38 months (95% CI 42–46 months) in patients with them (p = 0.1245). The median OS was 17 months (95% CI 10–35 months) in patients with extramedullary plasmacytomas and 13 months (95% CI 1–69 months) if soft-tissue components were detected in the bones of the lower extremities. CONCLUSION. The course of ndMM is complicated by bone plasmacytomas in 23 % of cases and extramedullary plasmacytomas in 1 % of cases. The antitumor response rate as well as the OS rates are similar in patients with and without bone plasmacytomas. Extramedullary lesions in MM are associated with extremely low rate of OS with the median not exceeding 17 months.
Among В-cell tumors, there are composite/discordant lymphomas characterized by either synchronous or metachronous development, however, a combination of nodular lymphocyte-predominant Hodgkin lymphoma with classical Hodgkin lymphoma is extremely rare. This paper documents a similar case. It provides evidence for ‘plasticity’ of B-cell precursors, which can initiate lymphoid tumor growth at various stages of B-cell differentiation.
Bruton tyrosine kinase (BTK) inhibitors have drastically changed the approaches to the treatment of B-cell chronic lymphoproliferative diseases (LPD) as they considerably improve survival rates and quality of life of patients. Despite of their high efficacy, about half of the patients develop resistance to covalent BTK inhibitors due to point mutations in the BTK gene on the substrate binding site. This paper systematically reviews the present-day knowledge of mechanisms underlying the resistance to BTK inhibitors and methods to overcome it as well as the effect of these drugs on T-lymphocytes and tumor microenvironment cells in LPDs. It is demonstrated that non-covalent BTK inhibitors can sustain their activity against mutated BTK forms, whereas some degraders enable selective BTK protein breakdown irrespective of mutation status. Moreover, BTK inhibitors produce a considerable effect on tumor microenvironment, i.e., they reduce the number and activity of myeloid suppressor cells, foster changing polarization of macrophages from pro- (M2) to antitumor (M1) phenotype, and increase functional activity of T-lymphocytes by shifting the balance from Th2 to Th1. Consequently, immunomodulatory properties of BTK inhibitors contribute to antitumor immune response and can be successfully exploited in the combined treatment, also as a part of infection and inflammation therapy.
BACKGROUND. РOEMS syndrome is a rare multisystem syndrome associated with monoclonal proliferation of plasma cells or B-lymphocytes and based on cytokine-mediated pathogenetic mechanism. Despite the clear diagnostic criteria, timely verification of the diagnosis is challenging due to the extreme variability of clinical features. AIM. To study clinical and laboratory profile as well as diagnostic routes of patients with РOEMS syndrome. MATERIALS & METHODS. This retrospective observational study enrolled 40 patients with newly diagnosed РOEMS syndrome treated at two major centers for hematology in the period from 01.2016 to 09.2025. RESULTS. On the date of POEMS syndrome diagnosis, the median age of patients was 58 years (range 28–80 years), and median time from symptom manifestation to diagnosis was 23 months (range 1–146 months). On initial presentation at the Federal center, 30 % of patients were severely disabled and completely immobilized. All of them met two essential criteria: polyneuropathy and monoclonal gammopathy. In the vast majority of cases, polyneuropathy manifested itself in a sensory and motor form (87.5 %) with predominantly mixed axonal and demyelinating lesions (79.4 %). Paraprotein was identified in 97.5 % of patients, however in 30 % of them the pathologic clone of plasma cells was not detected by standard techniques. Other manifestations of POEMS syndrome include bone abnormalities (62.5 %), increased VEGF level (73 %), organomegaly (75 %), endocrinopathy (60 %), skin lesions (52.5 %), extravascular fluid overload (47.5 %), and thrombocytosis/polycythemia (45 %). Prior to diagnosis verification, on average, patients were examined by 3 (range 1–6) medical specialists, most often by a neurologist (62.5 %). At the diagnostic stage, chronic inflammatory demyelinating polyneuropathy (32.5 %) was widely and wrongly assumed. After examination by related specialists, 80 % of patients were referred to a hematologist. In 50 % of cases, lymphoproliferative diseases were identified, however, without verification of POEMS syndrome. In 20 % of patients, myeloproliferative neoplasia was wrongly diagnosed. CONCLUSION. For timely diagnosis of POEMS syndrome, medical specialists should raise awareness and alertness concerning its polymorphic clinical features and additionally strengthen interdisciplinary approaches.
A growing demand for transfusion therapy in hematologic patients as well as a limited bed capacity in profiled inpatient hospitals call for optimization in the field of specialized medical care and patient-oriented care models. This involves particularly the development of inpatient-equivalent treatment technologies enabling a greater number of patients to be treated in day-care units. In the period of 2017–2024, the replacement therapy using donated blood components was administered to 1,847 hematologic and oncologic patients. With a view to assessing the transfusion replacement efficacy in outpatient units, the analysis was conducted on medical records of 1,282 hematologic patients hospitalized at the Novosibirsk Clinical Blood Center. To treat anemia syndrome, 7,500 transfusions of donated blood components were employed, they included 6,495 transfusions with red cell components and 1,005 transfusions with platelet concentrate. In hematologic patients, the clinical efficacy was reached in 99.2 % of red cell-containing and 87.4 % of platelet-containing transfusions. Therapy management in a day-care unit has its own characteristics, at the same time, it allows the medical professionals to vary the length of inter-transfusion intervals and to plan subsequent hospitalizations for patients who need prolonged and repeated transfusions. Additionally, it facilitates the routing to specialized healthcare institutions for timely initiation of the next stage of specific therapy.
Myeloproliferative neoplasms (MPNs) refer to a range of chronic oncohematologic clonal diseases characterized by excessive proliferation of myeloid lineage cells and/or excessive fibrosis of the bone marrow. Although MPNs are commonly diagnosed in subjects over 60 years of age, it is now increasingly detected at a young age. It is not uncommon for practitioners to encounter young pregnant patients with Ph-negative MPNs. Both pregnancy and Ph-negative MPNs are characterized by hypercoagulation increasing the risk of thrombotic complications and other adverse events associated with placental insufficiency. Pregnant MPN patients are treated with antiaggregants (aspirin) and anticoagulants (low molecular weight heparin), erythrocytapheresis or bloodletting; interferon-α is used if cytoreduction is required. This paper reports a case of management and outcomes of four pregnancies in a patient with masked polycythemia vera marked by portal vein thrombosis, portal hypertension, splenomegaly as well as esophageal and gastric fundus varices. Her first pregnancy ended in miscarriage at the early stage of gestation, her second pregnancy resulted in a premature birth, whereas her third and fourth pregnancies were successful — she delivered full-term babies. During all pregnancies, the patient received interferon-α.
BACKGROUND. Escape of leukemia cells from immune surveillance appears to be one of the most relevant areas in the study of resistance mechanisms in chronic myeloid leukemia (CML). AIM. To study the characteristics of the NK-cell immune response in patients with chronic phase (CP) CML on third-line therapy with tyrosine kinase inhibitors (TKIs) of the second generation. MATERIALS & METHODS. The study enrolled 40 CML CP patients receiving third-line therapy at the VA Almazov National Medical Research Center. The control group consisted of 20 healthy subjects (HS). The quantitative characteristics of NK- and TNK-cells as well as the expression of activating and inhibitory receptors on NK-cells were assessed using flow cytometry. KIR (Killer cell Immunoglobulin-like Receptors) haplotypes were analyzed by PCR and electrophoresis of PCR amplification products. RESULTS. Irrespective of treatment response, CML patients showed no significant differences regarding either the quantitative characteristics of NK- and TNK-cells or activating and inhibitory receptors on NK-cells. However, in the quantitative characteristics of inhibitory KIR alleles as well as in the expression of two activating KIR alleles (KIR2DS4 and KIR3DS1), significant differences were identified in HS vs. CML patients (p < 0.05). At the same time, the expression rate was similar in the groups with optimal response and therapy resistance (p = 0.25). There were also no significant differences in the rate of KIR haplotypes in HS and two groups of patients. In most CML patients as well as in HS, Bx haplotype of KIR was identified. The percentage of deaths was higher in the group with A haplotype (4/9; 45 %) vs. Bx haplotype (4/31; 13 %) (p = 0.008). The median progression-free survival (PFS) in the A haplotype subgroup was 76 (range 24–162) months vs. 69 (range 3–179) months in the Bx haplotype subgroup; the median overall survival (OS) was 69 (18–179) months vs. 76 (24–159) months, respectively. CONCLUSION. No significant differences were revealed in the expression of activating and inhibitory receptors on NK-cells in both groups of patients with response to TKI third-line therapy and therapy resistance compared to HS. This study demonstrated that NK-cell immune response had no effect on complete cytogenetic response. The results of the study suggest that the assessment of NK-cell immune response and KIR haplotypes cannot be regarded as a valuable tool for predicting the treatment efficacy in CML CP patients. However, due to heterogeneity of the groups under this study, further research is necessary to understand the prognostic value of KIR haplotypes in achieving response to therapy as well as their effect on OS and PFS.
BACKGROUND. In the Russian Federation, systematic evidence of treatment outcomes and prognosis evaluation in primary CNS lymphoma (PCNSL) patients is currently unavailable. AIM. To study the clinical and epidemiological characteristics as well as current medical practice and the first-line therapy outcomes in PCNSL patients. MATERIALS & METHODS. The study enrolled 127 adults with histologically verified PCNSL diagnosis treated from 2010 to 2024 at nine medical institutions in Saint Petersburg. Absolute majority (n = 119; 94 %) of them received various regimens of chemo- and/or immunochemotherapy (ICT). High-dose methotrexate (HD-МТХ) protocols were administered in 103 (87 %) cases, 86 % (n = 101) of PCNSL patients received rituximab. RESULTS. Response assessment was analyzed in 111 (87 %) patients. Objective response (OR) to the first-line therapy was 72 % (n = 80) including complete remissions in 38 (34 %) patients. With the follow-up of 12 months (range 0.4–151.1 months), the 2-year overall survival (OS) was 43 % (95 % confidence interval [95% CI] 34–54 %), and the 2-year event-free survival (EFS) was 30 % (95% CI 22–40 %). Prognostic factors included ECOG status and HD-МТХ administration. After ICT, 28 (38 %) patients with OR received radiation or high-dose therapy with autologous hematopoietic stem cell transplantation as consolidation treatment. Consolidation stage, irrespective of the chosen option, was associated with better rates of long-term survival: the 2-year OS was 78 % (95% CI 62–100 %), the 2-year EFS was 59 % (95% CI 41–84 %). CONCLUSION. The clinical profile of PCNSL patients, as revealed in this study, is generally consistent with published literature. Most patients received the treatment regimens in accordance with the international guidelines, however, in a part of them, suboptimal treatment was used. The best rates of long-term survival were reported in patients who achieved OR and subsequently received consolidation therapy.
BACKGROUND. For more than 20 years, the standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) has been the R-CHOP regimen. However, about 30–40 % of patients experience relapsed/refractory disease. In the randomized POLARIX study, polatuzumab vedotin-based regimen (Pola-R-CHP) demonstrated a significant progression-free survival advantage over the standard R-CHOP. Yet, the evidence on the use of Pola-R-CHP in the real-world clinical practice in the Russian Federation is currently missing. AIM. To assess the efficacy and safety of the Pola-R-CHP regimen in patients with newly diagnosed DLBCL in a real-world setting in the Russian Federation. MATERIALS & METHODS. The multi-center retrospective study enrolled the data from 84 patients (48 men and 36 women) with immunomorphologically verified DLBCL diagnosis treated with polatuzumab vedotin-based first line therapy at 30 medical institutions of the Russian Federation in the period of 2022–2026. The median age of patients was 63 years (range 22–87 years). In 88 % of patients, DLBCL grade 3–4 was reported, 86 % belonged to a high-risk (IPI ≥ 3) group. The primary endpoint was complete response (CR) and overall response (OR) rate after 6 therapy cycles. Secondary endpoints included overall survival (OS), progression-free survival (PFS), metabolic response reported by PET/CT, and the analysis of safety profile. RESULTS. Full treatment was completed by 68 (81 %) out of 84 patients. After treatment, CR was 80.9 % and OR was 95.0 %. By PET/CT, complete metabolic response was achieved in 47/60 (78 %) patients. The median follow-up was 15.5 months. Neither median PFS nor median OS were achieved; the 2-year PFS was 82.5 % and the 2-year OS was 85.0 %. Most common adverse events (AEs) of any grade were neutropenia (67 %), leukopenia (55 %), anemia (35 %), and febrile neutropenia (14 %). AEs ≥ grade 3 were reported in 31 % of patients. CONCLUSION. In the real-world clinical practice in the Russian Federation, the Pola-R-CHP regimen showed high efficacy and favorable safety profile in the first-line therapy for DLBCL, also in the population of high-progression-risk patients. The results of the study are consistent with international data and prove the feasibility of risk-adapted treatment for DLBCL.
Langerhans cell sarcoma (LCS) is a rare high-grade malignant tumor consisting of Langerhans cells and characterized by aggressive course and high mortality. The incidence rate is 2 cases per 100 million population. As opposed to Langerhans cell histiocytosis (LCH), LCS is marked by pronounced cell atypia and tendency towards rapid metastasis. Clinical manifestations vary depending on the lesion location and involve skin, lymph nodes, bones, lungs, liver, spleen, and bone marrow. Due to the rarity of this disease, there are no standardized treatment protocols. The approaches used in LCH therapy are not effective in the treatment of LCS. The present paper reports a case of LCS with intensified chemotherapy regimens similar to those used in highly aggressive lymphomas including subsequent maintenance therapy which is commonly administered to high-risk LCH patients. This therapeutic strategy resulted in the complete LCS remission which has sustained for over 10 years.
The use of tyrosine kinase inhibitors (TKIs) dramatically improved long-term survival rates in chronic myeloid leukemia (CML) patients. Despite high specificity for BCR::ABL1 tyrosine kinase, TKIs can induce adverse events including increased risk of cardiovascular complications. One of the cardiovascular risk factors is an elevated homocysteine (HC) level. However, neither homocysteine status nor hyperhomocysteinemia effect on the disease course in CML patients on TKI therapy have been sufficiently studied. This paper aims to comprehensively analyze the current literature data on HC level changes and HC metabolism factors in CML patients. The review is based on the articles indexed in the PubMed, MEDLINE and other databases dealing with the mechanisms of HC metabolism genesis, transformation, and causes for its dysfunction in CML patients prior to and on therapy with TKIs of different generations. Despite the limited number of studies, a literature analysis suggests that HC level is a helpful marker of the folate cycle status, metabolic status, endothelial function, and tumor cell growth activity in CML patients.
Besides their key role in hemostasis, platelets are functionally involved in a variety of other processes (angiogenesis, vascular remodeling, inflammatory reactions, and immune responses) and, accordingly, contribute to numerous pathologic events. This review summarizes the current data on the profile of platelet matrix and regulatory, protein non-coding RNAs in some pathologic processes. Many publications focus on platelet transcriptome in oncologic diseases regarding it as a specific marker of ‘tumor educated platelets’ (TEP) and deal with promising diagnostic tests, such as liquid biopsy. The identification of RNA transfer from platelets to tumor cells gave rise to developing modified platelets and their microvesicles as potential therapeutics, also using small interfering RNAs. In this paper, special attention is given to diagnostic value of the platelet RNA profile in chronic myeloproliferative neoplasms because platelets subsequently show pathologically altered megakaryocyte transcriptome. In particular, it independently confirms the diagnostic value of the platelet mRNA of CREB3L1 gene being a highly sensitive and specific marker of Ph-negative myeloproliferative neoplasms. The evaluation of mRNA level with the V617F mutation in the JAK2 gene can be chosen as an alternative to the assessment of mutant allele load in leukocyte DNA. This review also discusses the existing methodological issues in performing analytical procedures which appear to be the main disincentive to the widespread use of laboratory tests for RNA determination in platelets.
AIM. To confirm the comparability of the biosimilar daratumumab BCD-264 (BIOCAD) with the reference drug Darzalex (Johnson & Johnson) in terms of efficacy and safety of the monotherapy for relapsed/refractory (r/r) multiple myeloma (MM). MATERIALS & METHODS. This paper is based on the double-blind prospective comparative randomized phase 3 clinical trial BCD-264-2/DARVIVA assessing the efficacy and safety of BCD-264 and Darzalex as monotherapy for r/r MM. Duration of the blind period was 24 weeks. The trial enrolled 252 r/r MM patients treated with proteasome inhibitors and immunomodulatory drugs. This paper documents the analysis of the data collected within the blind period when the therapy was administered to Group 1 and Group 2, whereby neither the investigators nor the patients knew which drug is being used in each of the groups. RESULTS. The primary end point of the study was overall response rate (ORR) in 24 weeks after therapy onset. In Group 1, ORR was 36.2 % and it was 32.0 % in Group 2; ORR ratio for Group 1/2 was 1.13 (95% confidence interval [95% CI] 0.80–1.60) and 0.88 (95% CI 0.63–1.24) for Group 2/1. This confirmed the hypothesis of BCD-264 being no less effective than Darzalex. Besides, an additional hypothesis of drug equivalence was proved true demonstrating also the comparability of the drugs across all secondary efficacy end points and safety parameters. The most common adverse events reported in both groups were leukopenia, neutropenia, lymphopenia, anemia, thrombocythemia, infusion-associated reactions, and pneumonia. CONCLUSION. Both drugs BCD-264 and Darzalex showed comparable efficacy and safety during the 24-week period in the BCD-264-2/DARVIVA trial as well as comparable immunogenicity and pharmacokinetic profile.
BACKGROUND. In 2024, the German Hodgkin Study Group (GHSG) published the unprecedented results of the HD21 trial on PET-guided program BrECADD for patients with advanced stages of classical Hodgkin lymphoma (cHL) showing the highest cure probability with the best tolerability. AIM. To review and analyze the first experience in Russia with BrECADD administered to patients with advanced stages of cHL in a real-world setting. MATERIALS & METHODS. Clinical data from 20 BrECADD recipients with advanced stages of newly diagnosed cHL were provided by 5 medical institutions from 3 cities in Russia. The median age was 31.5 years (range 19–43 years), there were 13 (65 %) female patients. PET/CT after 2 cycles (PET-2) was performed in 9 patients, 6 (66.6 %) of them showed complete metabolic response, which is similar to the results of the HD21 trial (64 %). PET-guided therapy was administered to only 5 patients (25 %), while in the rest of them the number of BrECADD cycles was determined by the attending physician regardless of whether an interim PET-2 was performed and irrespective of its results: 16 patients received 4 and 4 patients received 6 BrECADD cycles. Consolidating radiotherapy was administered to 4 cHL patients. RESULTS. After the chemotherapy stage, complete metabolic response was achieved in 16 (84 %) out of 19 patients (1 patient in clinical remission refused PET after chemotherapy completion), which is similar to the results of the HD21 trial (82 %), partial remission was identified in 1 and disease progression was observed in 2 patients. With the follow-up of 17.5 months, all patients were alive, progression-free survival was 90 % by that time. There were no cases of cycle or dose reduction due to adverse events. Increasing the intervals between cycles in 1/3 patients did not affect general therapy outcomes. CONCLUSION. The analysis of the first findings on BrECADD demonstrated its high efficacy, moderate toxicity, and feasibility in a real-world setting in Russia. The main issue appeared to be non-compliance with the HD21 recommendations in the majority of cases, that requires further standardization in the implementation of the program with a view to establishing best practices and identifying lessons learned with BrECADD administration in the routine practice of treating advanced cHL stages.
BACKGROUND. Clinical trials of glofitamab (Glofit) have demonstrated its high efficacy and tolerable toxicity profile in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients. However, the data on its use in a real-world setting remain sparse. AIM. To assess the efficacy and safety of Glofit in the combined cohort of R/R DLBCL patients in a real-world setting in the Russian Federation. MATERIALS & METHODS. This retrospective multi-center study enrolled 88 R/R DLBCL patients treated with Glofit under a compassionate use program from 2021 to 2024 in 22 Russian medical institutions. The median age of patients was 54 years (range 21–83 years), there were 42 (48 %) male patients. The main eligibility criteria were ≥ 3 prior therapy lines and exhaustion of available standard treatment methods. Glofit was administered as a monoregimen according to the schedule recommended in the package insert. RESULTS. With the follow-up median of 8.4 months (range 0.6–52 months), overall response was achieved in 46 (53 %) patients including 36 (42 %) patients with complete response (CR). The median overall survival (OS) was 13.1 months (95% confidence interval [95% CI] from 8.6 months to not reached), the 1-year OS was 55.7 % (95% CI 45.6–68.1 %). The median progression-free survival (PFS) was 4.2 months (95% CI 2.8–8.8 months), and the 1-year PFS was 33.5 % (95% CI 24.6–45.8 %). The median OS and PFS in patients with CR was not reached, whereas the 1-year PFS and OS were 73.7 % (95% CI 59.4–91.5 %) and 87.9 % (95% CI 77.4–99.9 %), respectively. Adverse events (AEs) were reported in 75 (85 %) patients, among them AEs of grade ≥ 3 in 35 (40 %) patients. Cytokine release syndrome was identified in 33 (38 %) patients, and “flare” syndrome was registered in 14 (16 %) patients. Infectious complications were observed in 45 (51 %) patients. Grade 5 AEs included only COVID-19 infection (n = 7; 8 %). Male gender, early relapse/refractoriness as well as 3-month administration of bendamustine prior to Glofit therapy were associated with the rate of achieving CR. PFS was lower in bendamustine recipients and also in cases with B-symptoms and massive tumor (bulky, > 7.5 cm). CONCLUSION. Glofit demonstrated high efficacy and tolerable toxicity profile in the treatment of R/R DLBCL patients. The results obtained in a real-world setting confirm the data from previously published clinical trials.
This paper reviews the available science literature to survey serious adverse events (SAEs) in hematopoietic stem cell donors (HSC). The data obtained and summarized provide a rich resource to inform potential donors about possible risks associated with different methods of HSC collection and additionally contribute to the development of effective approaches for the prevention of complications. The analysis suggests that the incidence of SAEs in bone marrow donors is 0.04–2.4 %. The most ubiquitous SAE are infectious, cardiovascular and cerebrovascular complications as well as mechanical damage. The SAE rate in peripheral blood stem cell collection is 0.1–1.1 %. The most common complications include infections, acute systemic toxicity during cell mobilization and collection, cardiovascular and cerebrovascular complications. The incidence of malignant neoplasms in HSC donors is not higher than in the general population.
Results of the 67th American Society of Hematology (ASH 2025) Annual Meeting: Their Importance for Practical Hematology
Fundamental studies of hematopoiesis have confirmed the existence of WT1-expressing lineage-differentiated hematopoietic precursor cells, which are functionally related with BAALC-expressing hematopoietic stem cells (HSCs), on the one hand, and with WT1-expressing blast elements, on the other. The data obtained provided the basis for analyzing the mixed cohort of patients with CBF-positive and FLT3-mutated variants of acute myeloid leukemia (AML) for developing a panel of molecular markers. The purposes of this panel are therapy efficacy assessment and early diagnosis of relapses alternative to the initial BAALC-expressing HSC clones. The developed combined approach was tested on a big clinical case series including the data from 114 patients with CBF+ (n = 63) and FLT3+ (n = 51) AML variants. The suggested original molecular diagnostic panel based on the serial measurements of BAALC and WT1 expression levels combined with simultaneous determination of the blast content in bone marrow aspirates seems to be a promising and useful tool for both research and clinical practice.
