Background. Recently, digital technologies have been increasingly being used worldwide to monitor patient-reported outcomes in routine clinical practice. Electronic systems allow in a convenient way, remotely, with obvious savings in time and resources, to carry out an automated assessment of the patient's individual response to disease and treatment.

We aimed to develop and test an interactive ePRO system for quality of life (QoL) and symptom monitoring in patients with hematological malignancies (HM) in a clinical setting.

Methods. At the first stage, an electronic system “Health - Electronic Self-Assessment” (HESA) was developed based on a secure Internet resource using two special questionnaires - HM-PRO and HADS. At the second stage, patients with HM filled out questionnaires using HESA at admission to the hospital, after treatment and remotely at different times after discharge. The data was processed using descriptive statistics methods.

Results. The interactive electronic system HESA was developed, providing the possibility of graphical visualization of patient-reported outcomes to patients and clinicians in a real time. In the total, 115 patients participated in the testing of HESA (mean age - 44.0 years, 55% - women), with different HM, receiving high-tech medical care. Half of the patients filled out questionnaires by HESA remotely at different times after discharge. Treating physicians had the ability due to HESA to monitor changes in different aspects of QoL and psychological problems in patients based on graphs, summary results and patient comments.

Conclusion.As the result, the first domestic electronic system HESA was developed for QoL monitoring in patients with HM in a routing clinical practice. It was demonstrated that HESA is a valuable approach to inform hematologists about changes in QoL and symptoms in inpatients and outpatients’ settings to facilitate shared decision-making and foster holistic patient care.

Aim. To study the plasma blood concentration of tyrosine kinase inhibitors (TKI) in patients (pts) with chronic myeloid leukemia (CML) at standard and reduced doses, to assess the effect of the TKI plasma blood concentration on the loss of previously achieved major molecular response (MMR) and deep molecular response (DMR) after reducing TKI dose and to assess the effect of the TKI plasma blood concentration on the presence of adverse events (AE) at different doses of TKI and its resolution after reducing the TKI doses.

Materials and methods. The concentration of imatinib and nilotinib was analyzed in CML pts included in a prospective follow-up study of on TKI therapy with reduced doses by follow-up without therapy (READIT-2020, NCT 04578847). The 103 pts were included in the study. The study of the TKI concentration was performed in 46 pts on imatinib therapy and 16 pts on nilotinib therapy. There were studied the residual TKI plasma concentration ( C_trough, 24 ± 3 hours after the last drug intake) and the maximum TKI plasma concentration (C_max - 3 hours after the last drug intake). The C_trough was determined only on therapy with standard doses of TKI, C_trough and C_max  - on therapy with reduced doses of TKI. The determination of C_trough and C_max was performed by high-performance liquid chromatography (HPLC) - tandem mass spectrometry. The C_trough of imatinib was analyzed in 104 samples, C_max – in 63 samples. The C_trough of nilotinib was analyzed in 22 samples, C_max – in 15 samples.

Results. The mean value of C_trough of imatinib at a dose of 400 mg, 300 mg and 200 mg was 1092 ± 346 ng/ml, 809.5 ± 313 ng/ml and 570.9 ± 280 ng/ml, respectively. The mean value of C_max of imatinib at a dose of 300 mg and 200 mg was 1944 ± 577 ng/ml and 1233.4 ± 44 ng/ml. The mean value of C_trough imatinib at dose 300 and 200 mg was 773.5 ± 303 ng/ml and 586.3 ± 308 ng/ml in the group of pts without loss of DMR. The mean value of C_max imatinb was 1866.5 ± 532 ng/ml and 1283.7 ± 481 ng/ml, respectively. The mean value of C_trough imatinib at dose 300 mg and 200 mg was 774.8 ± 553 ng/ml and 490.6 ± 175 ng/ml  in the group of patients with DMR loss. The mean value of C_max imatinib was 2246 ± 1171 ng/ml and 1124.7 ± 281 ng/ml, respectively. There was no significant difference between the groups.
The mean value of C_trough imatinib at a dose 400 mg was 1120.6 ± 303 ng/ml and 998.4 ± 402 ng/ml in the group of pts with AE and without AE (p= 0.09). The proportion of pts with AE was higher (90%) in the group of pts with C_trough imatinib 400 mg > 1287 ng/ml.
The mean value of C_trough nilotinib at a dose 600 mg, 400 mg and 200 mg was 651.4 ± 397 ng/ml, 468.7 ± 220 ng/ml and 376.7 ± 151 ng/ml, respectively. The mean value of C_max nilotinib at a dose 400 mg and 200 mg was 655.3 ± 189 ng/ml and 628 ± 293 ng/ml.

Conclusions. There were significant differences in the C_trough and C_max of imatinib at standard and reduced doses. There were no significant differences in C_trough and C_max of nilotinib at standard and reduced doses. There was found that the C_trough of imatinib was significantly higher in the group of female patients than in the group of male patients (p=0.003). There were no significant differences in C_trough and C_max of imatinib in plasma at a dose of 400 and 300 mg in the groups of patients with and without AE. However, the proportion of patients experiencing drug toxicity was higher in Q4 and amounted to 90% (where Q1 included patients with the lowest C_trough values of imatinib 400 mg and Q4 - the highest).

Drug-induced sarcoid-like reaction is a granulomatous inflammation, clinically and morphologically similar to sarcoidosis, that typically develops against the background of anti-cancer chemotherapy and immunotherapy. An important feature of the drug-induced sarcoid-like reaction is its temporal association with the administration of drugs, including its reversal after their discontinuation. The development of sarcoid-like reactions has been described in the context of therapy with immune checkpoint inhibitors, interferon agents, tumor necrosis factor alpha antagonists, antiretroviral drugs, BRAF inhibitors, and rituximab. However, no reports have been made regarding sarcoid-like reactions associated with CD38 monoclonal antibody therapy, despite extensive experience in their use for plasma cell tumors. This article presents the first clinical observation of a sarcoid-like reaction with lung involvement, developed during daratumumab therapy in a patient with multiple myeloma and systemic AL amyloidosis. As a result of therapy using daratumumab, bortezomib, cyclophosphamide, and dexamethasone, a complete hematological response was achieved, as well as a clinical response in the form of improved heart, kidney, and liver function. However, 11 months after the start of therapy (at the stage of maintenance therapy with daratumumab), coalescing large-nodular lesions began to appear and rapidly increase in the right lung. At the same time, there were no clinical or laboratory signs of inflammation. For diagnostic purposes, thoracotomy was performed with the excision of the affected lung area, which had a dense-elastic consistency. Histological examination revealed epithelioid cell granulomas with numerous multinucleated giant cells, which was interpreted as a sarcoid-like reaction. After discontinuation of daratumumab therapy, the pathological changes in the lungs underwent complete regression without additional treatment within 4 months. The presented case proves the possibility of developing a sarcoid-like reaction during daratumumab therapy. Further research is necessary to understand the pathogenesis of such disorders.

Aim. To study the cellular composition of bone marrow lymphocytes, their immunophenotype, and the expression of immune checkpoints PD-1, PD-L1 and LAG-3 in patients with chronic lymphocytic leukemia with different responses to chemoimmunotherapy.

Materials and methods. In the bone marrow aspirate of 33 patients with chronic lymphocytic leukemia (CLL) before treatment and after 6 courses of chemoimmunotherapy, the immunophenotype of lymphocytes with expression of PD-1, PD-L1 and LAG-3 was studied using flow cytometry. Hematological response to treatment was assessed by minimal residual disease (MRD) value. Patients were divided in 2 groups: I (n=20) – with a good hematological response (MRD<1%), II (n=13) – with an unsatisfactory response (MRD≥1%). Statistical processing of the results was carried out in Statistica 13.0.

Results. Before treatment, the number of leukemic cells expressing PD-1, LAG-3, CD38, ZAP-70 in group I was lower than in group II; after treatment, their decrease was more pronounced. Among bone marrow T cells before treatment in group I, a higher level of CD3+, CD4+ and CD8+, CD8+CD28+, CD8+CD28-, CD8+CD38+ populations was noted, including those expressing PD-1, but not PD-L1 and LAG-3 . After treatment, the content of CD3+, CD4+, CD8+, T-regs, CD8+CD28+, CD8+CD28-, including PD-1+, increased in both groups, but was more pronounced in group II; the expression of LAG-3 on CD3+ and CD4+ lymphocytes retained in group II. Before treatment, in all patients with CLL the level of NK cells was reduced, after treatment prevailed CD3-/CD16+/CD56+, CD3-/ CD16+/CD56+/PD-1+ cells and were reduced CD3-/CD16+/CD56+/LAG-3+ cells in group I. PD-L1 expression on NK cells was not detected, was insignificant on T and B cells it before treatment and was not detected at all after it.

Conclusion. Initially elevated levels of tumor LAG-3+ and PD-1+ B cells in the bone marrow of CLL patients predict MRD persistence after therapy. Overexpression of these markers on T- and NK-lymphocytes of patients with MRD-positive status after treatment indicates their functional defect.

Rationale. The most common point mutations in multiple myeloma (MM) are mutations in the KRAS and NRAS genes. The prognostic significance of mutations in these genes in MM has been investigated in a series of studies, but the results are contradictory.

Aim. To determine the oncogenicity of mutations in the KRAS and NRAS genes in new diagnosed MM patients and to classify them according to their influence on the depth of response to bortezomib-containing induction regimens.

Methods. Eighty-nine patients with new diagnosed MM were included in this study.  Bone marrow (BM) plasma cells were isolated from BM aspirates by Ficoll gradient centrifugation with subsequent immunomagnetic positive selection for the CD138 marker. Mutations in the KRAS and NRAS genes in CD138+ cells were detected by Sanger sequencing. Mutation Taster, Polyphen2, FATHMM-XF proteomics programmes were used to evaluate the oncogenicity of the mutations.  Depth of response was assessed after 6 courses of bortezomib-containing regimens. Statistical analysis was performed using SAS package procedures.

Results. The RAS genes harbored mutations in 42% (37/89 patients). We found that the mutations in RAS genes negatively affected the efficacy of induction therapy with bortezomib-containing regimens (p=0.008, OR = 3.5 (CI95% 1.32-9.08)).  Analysis of mutations in Mutation Taster, Polyphen2, FATHMM-XF showed different levels of oncogenicity, but there was no statistically significant difference in response to therapy between patients with "high-risk» mutations and patients with other mutations. Based on clinical data, we created a group of adverse mutations (NRAS Gly13Asp, Gln61His, KRAS Gly12Ala, Gly12Asp, Gly12Val, Gly13Asp, Gln61Arg, Gln61His, Ala146Val), from those patients who did not achieve a deep response to therapy (less than a very good partial response). The frequency of deep responses to bortezomib-containing regimens was significantly lower in the adverse mutation group than in the standard group (p < 0.0023, OR 14.9 (CI 95% 3.11-71.12)).

Conclusion. Mutations in KRAS and NRAS genes negatively affected the efficacy of induction therapy with bortezomib-containing regimens. According to our analysis, the adverse mutation variants were NRAS Gly13Asp, Gln61His, KRAS Gly12Ala, Gly12Asp, Gly12Val, Gly13Asp, Gln61Arg, Gln61His, Ala146Val.

In Russia, as well as throughout the world, over the past 20 years there has been a significant increase in people with excess body weight. According to various authors, the prevalence of obesity and overweight among the adult population ranges from 20.5 to 54%. Among men, the prevalence of obesity increased from 10.8% in 1993 to 27.9% in 2017, and among women from 26.4 to 31.8%, respectively. The pharmacokinetics of drugs, including cytostatics, differs in patients with excess body weight and normal weight, which is due to both changes in renal and hepatic clearance, and an increase in the volume of distribution of lipophilic drugs and increased protein binding. All these factors create certain difficulties in correctly calculating doses for obese patients, especially in cases of allogeneic hematopoietic stem cell transplantation, when the drug doses sublethal. In this review, we tried to consider modern approaches to the calculation of drugs and their rationale used in pre-transplant conditioning regimens in patients with underweight and excess weight.

Background: Inherited bone marrow failure syndromes (IBMFS) is a heterogeneous group of rare genetically determined diseases with variable hematologic and extra-hematologic manifestations. The introduction of highly specific genetic diagnostic methods has expanded the understanding of IBMFS beyond pediatric practice, which requires awareness of the clinical features and basic recognition signs of IBMFS in adult patients.

Aim. To characterize the clinical profile of adult patients with IBFMS.

Materials & Methods. The ambispective single-center study included 35 patients (25 males and 10 females) with a verified diagnosis of IBMFS and a median age of 26 years (range, 18-51). Distribution of IBMFS: congenital dyskeratosis (n=10, 28%), Diamond-Blackfan anemia (n=9, 26%), Fanconi anemia (n=7, 20%), GATA2 deficiency (n=3, 8%), GATA1 deficiency (n=1, 3%), amegakaryocytic thrombocytopenia (n=1, 3%), bone marrow failure (BMF) syndrome type 3 (n=1, 3%), severe congenital neutropenia (n=1, 3%), SAMD9 syndrome (n=1, 3%). The features of hematologic and extra-hematologic manifestations of IBFMS, the main steps and factors contributing to the diagnostic pathway were analyzed.

Results. Monolinear cytopenia, bilinear cytopenia and pancytopenia were present at hematological onset in 18 (52%), 6 (17%) and 11 (31%) patients, respectively. The median age of hematological onset was 15 years (range 0-43 years), in 14 patients (40%) cytopenia was first documented at the age of over 18 years. Morphological examination of the bone marrow revealed hypocellularity in 23 (63%) patients, whereas 7 (20%) and 5 (14%) patients had pure red cell aplasia and multilineage myelodysplasia, respectively. Chromosomal aberrations were present in 2 patients. The paroxysmal nocturnal hemoglobinuria clone was not detected in all 27 patients examined. During the follow-up period, 12 (34%) patients achieved the criteria for non-severe aplastic anemia. A temporary partial or complete spontaneous recovery of blood counts was recorded in 6 patients (17%). Developmental abnormalities with partial or complete organ dysfunction were detected in 14 patients; all patients had minor physical anomalies. All patients with Fanconi anemia and 9 of 10 patients with congenital dyskeratosis had specific organ defects. A family history was established in 15 patients (43%), mainly indicating the malignant neoplasms in relatives. IBMFS was suspected during the initial hematological examination in 12 patients (34%) with a median time to diagnosis of 6 months. In the remaining 23 (66%) cases, cytopenia was misinterpreted for a long time as a consequence of various acquired diseases, that led to a delay in establishing the correct diagnosis (median 7 years, p=0.0283). In the diagnostic path, organ abnormality and family history were the main factors that led to the suspicion of congenital etiology of BMF. The diagnosis of IBMFS was confirmed by next generation sequencing (NGS) in 29 patients (83%), and by other specific methods in 4 (11%). In 2 cases, the diagnosis was established only on the basis of full clinical criteria.

Conclusion. IBMFS is an actual and difficult to recognize clinical problem in adult hematological practice. Differential diagnosis between acquired and congenital BMF syndromes should be carried out regardless of the patient’s age. Detailed physical examination of patients, family history, critical analysis of the clinical phenotype and disease course allow timely suspicion of IBMFS. Clinical suspicion of IBMFS is an indication for referral of patients to specialized centers and genetic diagnostics, including NGS.

Introduction. Patients with hematological diseases represent an increased risk group for infection with the new coronavirus infection COVID-19, since, as a result of their immunocompromised status, antibodies of different classes against SARS-CoV-2 after the disease are often absent or their formation is insufficient.

Aim. To study the initial state of the humoral component of the adaptive immune system and its changes during standard therapy with monoclonal antibodies in hematological patients after COVID-19.

Materials and methods. The study included 51 patients with hematological diseases who were treated at the Federal State Budgetary Institution “GVKG named after. N.N. Burdenko". Lymphomas were diagnosed in 54.9% of patients, multiple myeloma (MM) - in 27.5%, acute leukemia - in 11.8%, myeloproliferative diseases (MPD) - in 5.8% of patients. The control group consisted of 16 hospital medical workers. In the main group, a separate subgroup of patients who received monoclonal antibody (MAB) therapy was identified - 21 patients (41.2%). All subjects underwent blood serum testing for the presence of antibodies of the IgM and IgG classes to the receptor-binding domain of the S1 protein and the nucleocapsid proteins of SARS-CoV-2 (semi-quantitative method with calculation of the positivity coefficient (CP) in arbitrary units), antibodies of the IgG class to S1 protein of SARS-CoV-2 (BAU/ml), neutralizing AT classes IgG, IgA, IgM to the receptor-binding domain of S1 protein of the SARS-CoV-2 virus (NAB, Au/ml).

Results. It was found that patients with lymphomas had lower values of IgG antibodies to the S-protein of SARS-CoV-2 compared to patients with other hematological diseases. Statistically significant differences were found in the lymphoma and MM groups, median 431 BAU/ml and 667 BAU/ml (p<0.05), lymphoma and MPZ, median 431 BAU/ml and 705 BAU/ml (p<0.05). When comparing the control and main groups, the median level of antibodies of the IgG class was the same value of 15.7 arb. units, the levels of IgG class antibodies to the S-protein of SARS-CoV-2 and NAB differed slightly, the median in the control group was 584 BAU/ml and 111.86 Au/ml, in the main group 603 BAU/ml 185.13 Au/ml , no statistically significant differences were found. When comparing groups of hematological patients who received chemotherapy using mAbs and those who received only standard chemotherapy, the median level of antibodies of the IgM and IgG classes to the receptor-binding domain of the S1 protein and the nucleocapsid proteins of SARS-CoV-2 was 10.1 arb. units, versus 16.1 conventional units. (p<0.05), when studied by a quantitative method, the median level of IgG class antibodies to the S-protein of SARS-CoV-2 is 433BAU/ml, versus 595 BAU/ml (p<0.05).

Conclusion. Analysis of the data obtained confirmed that in patients with hematological pathology, antibodies are formed worse in response to COVID-19 NCI compared with the general population; there is a decrease in both IgG antibodies to the SARS-CoV-2 S protein and NAB. Patients not receiving mAb therapy have a higher level of IgG antibodies to SARS-CoV-2, determined by three research methods, which was statistically significant. In this regard, hematological patients requiring MCA therapy require prevention of NCI infections: vaccination before starting chemotherapy or the use of recombinant human monoclonal antibodies of the IgG Ik class tixagevimab + cilgavimab.

Introduction. Immune thrombocytopenia (ITP) is an acquired immune-mediated disease characterized by isolated transient or persistent thrombocytopenia < 100 × 109/L. Various viral infections and sometimes prior vaccinations have been identified as triggers of ITP in childhood. The incidence of ITP is 4-6,4 per 105 children/year.

Aim. To evaluate the effectiveness of treatment of children with immune thrombocytopenia.

Materials and methods. The analysis included 13 patients (F-46%, M-54%, median age - 9.5 (4-17) years) with ITP admitted to the Tver Regional children hospital in 2023. A history of infection preceding the ITP was in 69% of cases and measles vaccination in 8%. The median period from the onset of infection was 11 (5-15) days. Degree of bleeding was - 1 gr. - 4 (31%), 2 gr. - 3 (23%), 3 gr. - 6 (46%). Hematuria was observed in 3 (23%), menorrhagia in 1 (8%) case. The mean platelet count at the time of admission was 9,0 (1.0-86) x109/l.

Results. The incidence was 5.7 per 105 children/year. Dexamethasone 20 mg/m2, days 1-3, was used in 54% of cases; IVIG 1000 mg/kg, day 1 in 15%, prednisolone 2 mg/kg, day 21 in 8% and in 23% of cases dynamic follow-up was performed. In 2 cases (17%), discontinuation of steroid therapy and switching to IVIG was required due to a hemorrhagic syndrome deterioration or/and complication of steroid therapy. Partial and complete responses were achieved in 8 (62%) and 4 (31%) cases respectively. In 1 (8%) case, the answer cannot be evaluated. The summary efficacy of first-line therapy was 92%. The median platelet count at discharge was 70 (20-307) x109/L and hospitalization days was 10.2 (2-23). A decrease in the amount of PLT to 1-2 degrees was observed in 23% in the first 6 weeks with spontaneous complete recovery during the next 1-2 weeks.

Conclusion. The clinical guidelines ID699 was highly effective in achieving a primary response and preventing recurrence of ITP in children. The combined frequency of IVIG use (31%) in our study is due to a slow response to steroids, an increase in hemorrhagic syndrome, the presence of risk factors, as well as parental anxiety.

Introduction. The heart is the main target organ in systemic AL amyloidosis. The clinical features and prognosis of systemic AL amyloidosis with cardiac involvement are not well understood and require a multidisciplinary approach.

Materials and methods. The analysis included 123 patients with heart damage due to systemic AL amyloidosis, identified since January 2004 until July 2023 at the RM Gorbacheva Research Institute.

Results. Stage I, II, IIIa and IIIb heart disease was detected in 13.8%, 50.4%, 17.9% and 17.9% of patients, respectively.
Chronic heart failure (CHF) eveloped in 65.9%, of which severe degree - in 25.4% of patients. 90.2% of patients, despite the presence of CHF, had preserved left ventricular ejection fraction (EF) (>40%), the average value for EF was 59.6% (33 – 78%).
The left ventricular stroke volume index (LVSI) was reduced (<41 ml/m2) in 92.7% of patients, the average value for LVSI was 26.1 ml/m2 (8.3 – 49.5). LVSI decreased depending on the stage of cardiac damage: 30.9 ml/m2, 26.8 ml/m2, 24.8 ml/m2 and 21.4 ml/m2 for stages I, II, IIIa and IIIb, respectively (p = 0.006) .
The total global strain (GS) was increased > -20% in 94.6% of patients, the average GS was -13.8% (from -34.8% to -4.4%). Longitudinal strain worsened with increasing cardiac stage with a mean of -17.8%, -14.6%, -13.1% and -9.6% for stages I, II, IIIa and IIIb, respectively (p=0.007).
Atrial fibrillation was recorded in 23%, supraventricular tachycardia – in 31.9%, supraventricular extrasystoles – in 39.7% of patients. Ventricular extrasystole was observed in 73.7%, ventricular tachycardia – in 13.2% of patients. Sinoatrial block was registered in 6.6%, atrioventricular block – in 19.8% of patients.
Syncope occurred in 12.3% of patients. An artificial cardiac pacemaker (APM) was installed in 8 patients. The need to install an APM correlated with the severity of cardiac damage (p=0.003).
The incidence of thromboembolic complications was 13%, 11.4% of patients suffered myocardial infarction, 5.7% suffered acute cerebrovascular accident. Thrombi in the atria were detected in 2 patients (1.6%).
The 2-year cumulative rate of achieving hematological response was 56.96% and did not depend on the stage of cardiac damage (p>0.05). The 2-year cardiac response rate was 39.1%. 26.5% of patients died before a hematological response was achieved and 29.9% died before a cardiac response was achieved.
5-year overall survival was 62.6%, survival without hematological progression and deterioration in major organs was 39.3%.
Cox regression analysis confirmed 3 independent predictors of unfavorable outcome: NT-proBNP level ≥ 2500 pg/ml (RR=3.231, 95%CI 1.455-7.144, p=0.004), stroke volume index <25 (RR=2.312, 95%CI 1.159-4.611, p=0.0174), history of syncope (RR=2.883, 95%CI 1.19-6.986, p=0.0191). The development of hematological response to therapy had a positive effect on survival outcomes (HR 0.073, 95% CI, 0.033-0.162, p < 0.0001).

Conclusion. A comprehensive assessment of cardiac damage in AL amyloidosis at the onset of the disease and adequate cardiac therapy can reduce the risk of early mortality due to cardiac causes, and therefore increase the chance of achieving a hematological response and survival.

Aim. A study was conducted to develop an information system for hematologists to effectively select therapy via modeling and predicting treatment response based on the clinical profile of a patient with multiple myeloma (MM).

Materials & methods. A total of 142 therapeutic options and 53152 MM patients were included in the analysis based on 290 academic medical publications between 2003 and 2023. According to the patient's clinical profile and the therapeutic option, the Monte Carlo method was used to predict the efficacy of therapy by calculating the probability of a very good partial response or better.

Results. An interactive online application has been developed that predicts treatment response based on specified conditions and visualizes the results as a ranking of therapeutic options in real-time. Besides the patient's clinical profile, which is considered when selecting therapies, it is also possible to select trials based on their type and number of patients. The M-BOT application is available at oncotriage.ru.

Conclusion. Based on Monte Carlo simulation, treatment recommendations are consistent with physician decisions in real practice but allow us to significantly expand our possibilities for searching for reliable scientific information rapidly. As a result, this approach may become the primary tool for individual and collegial medical decision-making, as well as for predicting the effectiveness of multistage treatments for relapsed and refractory MM patients.

Relevance. Diffuse B-cell lymphoma (DBCL) is an aggressive, clinically and biologically heterogeneous tumor. In recent years, the role of the microenvironment in the carcinogenesis of DBCL has been extensively studied. Components of the extracellular matrix and a wide range of tumor-associated cells influence tumor proliferation, contribute to evasion of immune surveillance, and resistance to treatment. Cytotoxic T lymphocytes (CD8+) play a leading role in the formation of the immune response to intracellular pathogens or transformed cells.

Aim. To evaluate the prognostic value of the relative number CD8+ T-lymphocytes of the microenvironment in DBCL.

Materials and Methods.  124 patients with first diagnosed DBCL were included in the study. All patients received standard first-line polychemotherapy according to the R-CHOP scheme. The relative number of CD8+ T-lymphocytes in biopsy specimens of lymph nodes or other tumor tissue was determined using immunohistochemical and morphometric methods. Frequency analysis of data was performed using Pearson's chi-square test (χ2), five-year overall (OV) and progression-free survival (PFS) were calculated using the Kaplan-Meier, Cox regression method.  The threshold value for CD8+ T cells was calculated using ROC analysis.

Results. The prognostically significant threshold level of CD8+ T-lymphocytes in biopsy specimens corresponded to 13%. A subthreshold number (CD8≤13%) of cytotoxic lymphocytes was associated with the presence of extranodal lesions in patients and lack of complete response to standard therapy, low OS and BPV compared to patients who had CD8+ T-cell content above the threshold level. The proportion of CD8+ T-lymphocytes below 13% is an unfavorable independent prognostic factor in the OV and LFTs of patients with DBCL treated with the R-CHOP protocol.

Conclusion. CD8+ T-lymphocyte count ≤13% is an unfavorable criterion to predict the course of diffuse B large cell lymphoma.

Histiocytosis from Langerhans cells refers to clonal diseases of the blood system. Patients with localized forms have a better prognosis because radiation or surgical treatment can be curative. If the process involves multiple organs, systemic chemotherapy can cure some patients. In this article a 40-year-old patient with a multi-focal, multi-system form of histiocytosis from Langerhans cells with lesions in bones, liver, spleen, abdominal lymph nodes and pituitary gland is described. Diagnosis was confirmed by histological and immunehistochemical analysis of the bone. PCR-test revealed no BRAF V600E mutation in the bone. He has got 6 cycles of cladribine chemotherapy. The tolerance was acceptable. A stable antitumor response has been achieved, which lasts for 30 months.