As is known, orphan diseases, which include histiocytosis, including Erdheim-Chester disease (ECD), occur under the guise of other diseases, which complicates timely diagnosis and treatment. The presence of various symptoms in patients with an unspecified diagnosis (weight loss, fever, chills, night sweats, malaise, shortness of breath, thirst, polyuria; pain in the muscles and joints, in the long tubular bones of the upper and lower extremities, in the lower back or abdomen due to kidney damage and/or retroperitoneal fibrosis; exophthalmos; rash, xanthomas; frequent infectious diseases; nystagmus, ataxia, dysarthria) requires doctors to be wary of BEC.The variety of symptoms is due to the involvement of many organs and systems (orbits, kidneys, skin, brain, including the pituitary gland; lungs; heart; blood vessels; tubular bones), which requires a thorough examination, including morphological verification of the pathological process. Histological examination of biopsy specimens for BEC is characterized by histiocytic infiltrates (so-called “foamy histiocytosis”) with signs of inflammation and the presence of Touton giant cells; Immunohistochemistry reveals positive staining of these giant cells for CD68 antigen and factor XIIIa. Bone scintigraphy reveals a pronounced symmetrical accumulation of radiopharmaceuticals in the affected bones; with radiography in places of ossalgia — significant symmetrical bilateral osteosclerosis of the periosteum; according to CT data - “hairy” kidneys, “lined” aorta as a result of infiltration with histiocytes. The BRAF V-600E gene mutation, detected in half of the cases, in combination with one or more clinical and morphological signs allows a correct diagnosis to be made. The treatment of this disease is quite complex due to the lack of multicenter international clinical studies due to the rare occurrence of this pathology. However, clinical studies are currently being conducted on the use of drugs of various groups in the treatment of BEC. There is no doubt that due to the rarity of the disease and the low awareness of doctors, our own clinical experience in managing such patients is of great interest.

Serum ferritin (SF) is typically present in serum at concentrations directly related to iron (Fe) storage and is therefore traditionally used as an indicator of Fe levels in body tissues. Reducing its level is the “gold standard” for diagnosing widespread iron deficiency conditions. No less significant is hyperferritinemia — a nonspecific syndrome that occurs when Fe reserves are overloaded, a number of immunoinflammatory, infectious, oncological diseases, liver diseases, etc. In many pathological conditions, the level of SF determines the severity and prognosis of the disease. Ferritin concentrations greater than 1000 ng/mL, regardless of cause, have been shown to be associated with higher mortality. The reason for the increase in the level of SF in liver pathologies (cancer, hepatitis, cirrhosis) is associated with the process of its release from hepatocytes during their destruction. On the other hand, excessive synthesis and/or cellular secretion of ferritin occurs under the influence of various stimuli (cytokines, oxidative stress, hypoxia, oncogenes and growth factors). The interpretation of elevated ferritin values goes far beyond the role of an indicator of replenishment of Fe stores in tissues. Only 10% of cases of hyperferritinemia are associated with iron overload; in most patients, it is defined as the result of the acute phase and a reactive increase in ferritin levels against the background of any disease. The variety of symptoms of iron deficiency syndromes and hyperferritinemia is due to the involvement of many organs and systems, which requires a thorough examination (study of complaints, anamnesis, family and concomitant diseases, as well as the necessary laboratory and instrumental studies) to search for possible causes. Systemic Fe homeostasis must be closely monitored on a regular basis. It is required to comply with the conditions for blood sampling for SF. Reference values for SF concentrations vary depending on the analytical methods used and the population studied. Age and gender play an important role. Given the range of reference values, it is important for a particular patient to focus on the initial level of his ferritin, determined against the background of health and well-being during clinical observation.

Currently, there is an increase in the number of publications, devoted to the problem of multiple primary tumors — neoplasms that occur simultaneously (synchronously) or alternately (metachronously), developing independently and independently of each other within the same or different organs. They are described as two, three or more nosologies. Due to the presence of defects in the immune system in chronic lymphocytic leukemia, solid tumors of different localization are a common finding. Their development is possible in other hematological diseases. This is probably due to success in the cure of tumor diseases, an increase in the life expectancy of patients, urbanization, an increase in the intensity of carcinogenic technogenic and medicinal effects, the presence of primary and secondary immunodeficiencies, as well as the use of modern diagnostic methods. Simultaneous detection of myeloproliferative and lymphoproliferative diseases in a patient is rare (in 1%), and this entails difficulties in diagnosing and prescribing therapy with such an association. In this regard, alertness is necessary in the presence of clinical and laboratory signs of a disease of the blood system that are not characteristic of the established type of hemoblastosis. And, of course, of undoubted interest is our own experience in managing such patients.

Thrombocytosis (an increase in the level of platelets in the peripheral blood above 450×109/l) has different causes and mechanisms of formation: it can be familial, primary (clonal), secondary (reactive). The ability to interpret peripheral blood parameters, knowledge of the main differential diagnostic criteria for diseases accompanied by thrombocytosis, allow the doctor to conduct the necessary examination to determine the cause of an increase in the platelet count in the blood. Clarification of the nature of thrombocytosis is very important, since clonal thrombocytosis is more often accompanied by the development of thrombotic complications and requires more active therapeutic intervention, specific therapy. Timely diagnosis helps to prevent the development of thrombosis, improves the prognosis, quality of life and survival of patients.

Purpose : to determine the optimal therapy regimens in patients with CLL, depending on age, comorbidity, prognostic (genetic) factors, clinical picture. Materials and methods: analysis of case histories of 400 patients with CLL observed at the Rostov State Medical University, Ministry of Health of the Russian Federation from 2010 to 2020. Results : Immunochemotherapy according to the FCR and FCR-Lite regimens has shown high efficiency in primary and pre-treated patients in terms of the frequency of achieving complete and partial remissions and achieving progression-free survival. In untreated patients, complete remissions were obtained in 61 (71.7%), partial remissions - in 14 (16.4%); among pre-treated patients, respectively - 40 (20.5%) and 65 (33.8%). Conclusion : combination therapy according to the FCR and FCR-Lite regimens is an affordable and effective method of treatment for most patients with CLL. When the level of leukemic blood cells with 17p13 deletion is less than 15%, rituximab should be used in the first line of immunochemotherapy, and ibrutinib (imbruvica) in case of more than 15%. In mono-regimen, rituximab is effective in supportive - anti-relapse therapy and in the treatment of autoimmune complications.

Imatinib mesylate is a potent and high selective inhibitor of Bcr-Abl tyrosine kinase, which is established now as the standard of Philadelphia chromosome positive (Ph) chronic myeloid leukemia (CML) treatment. The treatment of patients with chronic phase of CML with imatinib has resulted in high rates of hematologic and cytogenetic responses. Nevertheless, primary and acquired resistance have been observed in few CML patients. The mechanisms of resistance to imatinib and its clinical significance were discussed in this review.

Кidney injury is a frequent and significant complication of cancer and cancer therapy. The kidneys are susceptible to injury from malignant infiltration, damage by metabolites of malignant cells, glomerular injury, nephrotoxic drugs including chemotherapeutic agents. Also bone marrow transplantation complications, infections with immune suppression (including septicemia), tumor lysis syndrome should be taken into account. Chemotherapeutic agents are a common cause of acute kidney injury but can potentially lead to chronic kidney disease development in cancer patients. This article summarizes risk factors of acute kidney injury in cancer patients. Risk factors are divided into two groups. The systemic are decrease of total circulating blood volume, infiltration of kidney tissue by tumor cells, dysproteinemia, electrolyte disturbances. The local (renal) risk factors are microcirculation disturbances, drugs biotransformation with formation of reactive oxygen intermediates, high concentration of nephrotoxic agents in proximal tubules and its sensitivity to ischemia. Drug-related risk factors include: drugs combination with cytotoxic effect high doses long term use necessity, direct cytotoxic effect of not only chemotherapeutic agents but also its metabolites, mean solubility forming intratubular precipitates. Early diagnosis, timely prevention and treatment of these complications provide significantly improve nononcologic results of treatment.

Background. Due to the significant increase in life expectancy and the quality of life in patients with chronic myeloid leukemia (CML) as well as the growing need for expensive tyrosine kinase inhibitors (TKI), the analysis of cost-effectiveness and lifelong monitoring of patients is especially important. Aim. We present the results of a multicenter observational study “The Russian Registry of Chronic Myeloid Leukemia in routine clinical practice (2011-2016)”. Materials & Methods. The study included Russian patients with CML, confirmed by the detection of a Ph-chromosome or a BCR-ABL transcript. The statistical analysis (July 1, 2016) included 7609 patients from 80 regions of the Russian Federation (covering 95 % of the population). The annual increase in the number of patients with newly diagnosed CML was 600-650 patients. At the time of the statistical analysis, 6995 (92 %) patients remained under observation, 473 (6 %) died and 141 (2 %) were withdrawn. The registry included 44 % of men and 56 % of women, the median age was 49 years (range 2-94 years). The peak incidence (46.3 %) occurred at the age of 40-60 years. The median disease duration by the time of the analysis was 6 years (range 0.1-30 years). Results. The disease was diagnosed in the chronic phase (CP), acceleration phase, and blast crisis in 6560 (93.8 %), 380 (5.5 %) and 47 (0.7 %) patients, respectively. The proportion of risk groups according to Sokal for low, intermediate and high risk in CP was 49 %, 30 %, and 21 %, respectively. TKI were administered to 6473 (92.5 %) patients. Imatinib and the second generation TKI (TKI2) were administered to 5570 (86 %) and 903 (14 %) patients, respectively. The total of 30.4 % of patients received the increased imatinib dose of 600-800 mg. In the TKI2 group, 558 (61.7 %) patients received nilotinib and 345 (38.2 %) patients received dasatinib. The proportion of patients with completed molecular genetic studies (MGS) in 2014, 2015 and the first 6 months of 2016 amounted to 61 %, 58 % and 23 %, respectively. The proportion of patients with cytogenetic studies (CS) for the same period was 28 %, 26 % and 7 %, respectively. No CS or MGS data were presented for 34 %, 35 % and 63 % of patients during this period. Optimal molecular response and major molecular response (MMR) for TKI therapy were observed in 23 % and 58 % of patients treated < 12 months and > 12 months, respectively. When nilotinib was used in the second line, MMR was obtained in 42 % of patients, and a deep molecular response was obtained in 25 % of patients (BCR-ABL < 0.01 %). Conclusion. The high efficacy of TKI therapy was observed in the majority of patients with the possibility of achieving a minimal residual disease. The problems concerning untimely monitoring and suboptimal administration of second line treatment were identified. In general, the CML patient registry allowed the data integration of data and information management of population with CML in Russia.

A variety of clinical symptoms significantly impedes to diagnose of Langerhans cell histiocytosis. Both presented clinical cases demonstrate patients, who were treated by dermatologists with different diagnoses for a relatively long time. This indicates show a small awareness of physicians about histiocytosis, which leads to late diagnosis verification and the development of severe visceral lesions, most of which are already irreversible.

Purpose: to evaluate the eff ectiveness of diff erent chemotherapy variants of NHL patients.Materials and methods: the therapy of 64 B-cell NHL patients aged 21-83 (38 males and 28 females) has been analysed. Th e eff ectiveness of the treatment was evaluated aft er the third cycle of therapy and inductional course of treatment as well as aft er the completion of the entire treatment program.Results: general eff ectiveness of the treatment made 80% (20 patients), full remission made 52% (15 patients), partial remission made 28% (7 patients), stabilization was achieved in 2 cases (2 patients) (8%), in three cases (3 patients) there was progressiveness of the disease. In the structure of aft er-eff ects the prevailing ones were: hematologic toxicity III-IVst. (56% of the patients), infection (48% of the patients), hemorrhagic syndrome (13% of the patients).Summary: contemporary PCT’s conducted according to prognostic risk groups, allows to achieve high survival rates for the vast majority of patients with NHL.

Imatinib has shown the high effectiveness in chronic myeloid leukemia (CML) therapy. Recent papers have demonstrated that the achievement of complete cytogenetic response and major molecular response to imatinib therapy may be related with more than 1000 ng/ml imatinib plasma level. Trough plasma concentrations of imatinib (Ctrough) were detected in 551 samples of 442 CML patients. Blood samples were collected 24 b 3h after the last IM dose at 300 (n = 8), 400 (n = 337), 600 mg (n = 155) QD and 12 b 3h after the last IM dose at 800 mg BD(n = 51). Imatinib plasma concentration was determined by a validated LC/ MS/MS method. Rationales for imatinib blood level testing: the patient is not responding as well as the physician would expect, the physician suspects that the patient may be nonadherent to imatinib, the physician suspects that the patient may be experiencing a drug-drug interaction, the patient is experiencing unusually severe side effects. A result of nonadherence to treatment is one of the most important reason of treatment failure or suboptimal response to imatinib (n = 32; 5.8 %). The level of noncompliance increases with higher imatinib doses. Imatinib trough plasma level less than 1000 ng/ml were founded in one half of cases.

Imatinib mesylate is a potent and high selective inhibitor of Bcr-Abl tyrosine kinase, which is established now as the standard of Philadelphia chromosome positive (Ph) chronic myeloid leukemia (CML) treatment. The treatment of patients with chronic phase of CML with imatinib has resulted in high rates of hematologic and cytogenetic responses. Nevertheless, primary and acquired resistance have been observed in few CML patients. The mechanisms of resistance to imatinib and its clinical significance were discussed in this review.