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.
