More than 25 years ago, the discovery of imatinib, the first ATP-competitive inhibitor of BCR::ABL1, the driving oncoprotein of chronic myeloid leukemia, revolutionized patients life by transforming a fatal condition into a chronic disease. The review analyzes data on the effectiveness of chronic myeloid leukemia therapy with tyrosine kinase inhibitors and a number of provisions that require discussion and, possibly, revision at the present stage. The first clinical trials of imatinib, the first ATP- competitive inhibitor of BCR::ABL1, started in 1998, demonstrated extremely high therapeutic efficacy, impressively increasing the rates of relapse-free and overall survival in patients with chronic myeloid leukemia. The life expectancy of the overwhelming number of patients has become comparable to the life expectancy of the main population. Over the years, the arsenal of therapeutic agents for the treatment of chronic myeloid leukemia has been significantly enriched: three ATP-competitive tyrosine kinase inhibitors of the 2 nd generation have been created and approved for use, 2 drugs of the 3 rd generation: ponatinib, and the first allosteric tyrosine kinase inhibitor asciminib have been registered for the treatment of patients with the T315I mutation. Regular cytogenetic and molecular genetic monitoring makes it possible to adequately assess the volume of the leukemic clone and is an integral part of evaluating the effectiveness of therapy, allowing to control and maintain remission in a number of patients without the use of tyrosine kinase inhibitors. Today imatinib remains the key drug of the 1 st line of therapy, at the same time, the appointment of 2 nd generation tyrosine kinase inhibitors in the first line of therapy can lead to an earlier and deeper response. The choice of the drug for each individual patient, taking into account the best tolerability and maximum effectiveness, allows individualizing treatment and expanding the possibilities of therapy.

The prognosis of chronic myeloid leukemia (CML) has changed during the past two decades from a disease with an overall survival of 5 years only to one in which patients can enjoy a near normal life-expectancy. Such remarkable improvement in the patients’ outcome is mainly due to the introduction of imatinib into the clinic (the first approved tyrosine kinase inhibitor [TKI]), but also to the approvals of others TKIs. Currently, there are six TKIs available for CML treatment in clinical practice. The article discusses the effectiveness and safety of only the 2nd generation of ITCs, each of which has its own range of both adverse events and advantages when prescribed in the first or subsequent lines of CML therapy. Although a proportion of patients (around 25%) will be able to successfully discontinue TKI treatment after achieving a deep molecular remission, most of them will require to keep on treatment indefinitely. In such a situation, it is crucial for doctors caring for CML patients to be aware of which TKIs are available for each particular clinical situation, what can be expected from them, and how to manage their potential side effects. In the present review, we will briefly address these issues from a practical point of view.

Improving the quality of medical care is one of the priority objectives of the state policy, for the solution of which the resources of the national project «Healthcare» and its constituent federal projects are used. Purpose of the study is the development of high-cost, resource-intensive and socially significant healthcare industry, such as the Hematology service. The aim of this study was to assess the organization and state of the Hematology service in the Central Federal District (CFD) of Russia – the leader both in terms of population and in terms of the number of subjects included in it – which is necessary to develop organizational and methodological measures aimed at its improvement. Materials and methods. Official statistical data and analytical materials of Federal State Statistics Service, the Cancer Registry, open sources of information, data from check-out work of the National Medical Research Center for Hematology in СFD. Statistical data analyzed with the Excel‑2007 package. The main research methods: study and generalization of the available information, informationanalytical, statistical, bibliographic. Results. The analysis of the performance indicators of Hematology in the CFD identified its main components, taken together of which it is possible to assess the quality of the organization of the provision of specialized medical care with subsequent rating, and made it possible to identify key points for further improvement of the hematological service. Conclusions. The results of the study indicate the need for constant monitoring of the main indicators of the Hematology service (staffing, bed fund, availability of specialized high-tech research methods for the blood system diseases), taking into account certain directions and the course of the state policy pursued in this direction.

Aim. To assess the efficacy and tolerability of asciminib in chronic myeloid leukemia (CML) patients after failure of ≥ 2 lines of tyrosine kinase inhibitors (TKIs) therapy under the МАР (Managed Access Program, NCT04360005) in Russia. Materials & Methods. The study enrolled 68 patients with Ph-positive CML chronic phase (CF), over 18 years of age, after failure of ≥ 2 lines of TKI therapy. The analysis was conducted on data from 50 patients who were followed-up for at least 3 months and did not undergo allo-HSCT. Dosing regimens were prescribed depending on T315I mutation. Asciminib 200 mg per os was administered twice a day to 20 patients with this mutation, and asciminib 40 mg per os was administered twice a day to 30 patients without this mutation. By the time of admission into the MAP, there were 42 (82 %) CF CML patients as well as 8 patients with second CF after accelerated phase (AF, n = 7) and myeloid blast crisis (BC, n = 1). None of them could be treated with any therapeutic alternative. 92 % of patients had received ≥ 3 lines of prior TKI therapy. Overall survival (OS) and discontinuation-free survival were estimated by the Kaplan-Meier method. A cumulative incidence function (CIF) was used to calculate the probability of achieving response. Multivariate analysis was based on Cox regression model. Results. The median asciminib treatment duration was 11 months (range 4–30 months). The probable 2-year OS was 96 %. After 12 and 24 months, discontinuation-free survival was 92 % and 70 %, respectively. On asciminib therapy, complete cytogenetic (CCyR/МR2), major molecular (MMR), and deep molecular (MR4) responses were achieved in 17 (42 %), 14 (30 %), and 9 (19 %) patients who had not responded to prior treatment at the point of enrollment. After completing the 12- and 24-month therapy, the probability of CCyR/МR2 achievement was 44 % and 62 %, that of MMR achievement was 32 % and 40 %, and that of MR4 achievement was 26 % and 37 %, respectively. The patients treated with different doses did not significantly differ in achieving either CCyR/МR2 or MMR. By multivariate analysis, the independently significant factor impacting the probability of achieving MMR on asciminib treatment was the best MR (BCR::ABL1 < 1 % vs. 1–10 % vs. ≥ 10 %) after prior TKI therapy (hazard ratio 7.5873; p = 0.0072). In 22 (44 %) patients, adverse events (AEs) of all grades were observed, and 8 (16 %) patients showed AEs grade 3/4 (predominantly thrombocythemia and neutropenia). None of the patients discontinued asciminib treatment due to AEs. Conclusion. Asciminib demonstrated highly promising efficacy in previously TKI-treated patients with T315I mutation (200 mg BID) and without it (40 mg BID). Asciminib can be regarded as therapeutic option after failure of other TKIs. Different doses of asciminib were equally well tolerated, which makes it applicable for patients with intolerance to other TKIs and also provides ground for considering dose increases in non-responders. Good prospects are also expected for studying asciminib efficacy at earlier treatment stages (in first or second lines) as well as in combination with ATP-binding TKIs in CML patients with insufficient response to TKI treatment.

Introduction. The option of observation without therapy with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) patients is already included in Russian and international clinical guidelines. Evaluation of long-term follow-up results of treatment free remission (TFR) in CML patients is relevant for the introduction of this approach into routine clinical practice. Aim — to demonstrate the outcomes in a long-term follow-up of CML patients who discontinued TKI therapy in the RU-SKI trial. Patients and methods. The prospective study included 98 CML patients with TKI therapy duration ≥ 3 years and a deep molecular response (DMR, BCR::ABL1 ≤ 0.01 %) duration ≥ 2 years. TKI therapy was resumed with the loss of a major MR (MMR, BCR::ABL1 > 0,1 %). Results. Median time of follow-up after TKI discontinuation was 64 months (range of 51–86 months). Survival without MMR loss at 3 and 5 years after TKI discontinuation was 51 % (CI 41–61 %) and 46 % (CI 36–57 %) respectively. From 3 to 5 years of follow-up without therapy, the loss of MMR occurred in 2 (4 %) patients. There was no MMR loss observed after 5 years of follow-up. In patients with first and second treatment discontinuation, survival without MMR loss was 50 % versus 12,5 %(р = 0,039). All 50 patients with molecular relapses regained MMR and MR4 after TKI therapy resumption. BCR::ABL1 level fluctuations 0,01–0,1 % were in 62 % (n = 29) patients, who were in TFR at the time of analysis. Loss of MR4 was observed in 38 (42 %) from 90 patients with first TKI discontinuation. Survival without MMR loss from MO4 loss was 24 % at 5 years after TKI discontinuation. Loss of MO4 in the first 3 months after TKI cessation was associated with a high probability of further MMR loss (8 % versus 54 % in patients with loss of MO4 for > 3 months, p = 0.00015). Conclusion. The low frequency of late relapses (4 % after 3 years of follow-up) and the possibility of long-term persistence of minimal residual disease (MRD) after discontinuation of therapy determine the need to optimize the timing of molecular monitoring, taking into account the MRD status of patients.

Introduction. As part of the implementation of the federal project Development of a network of national medical research centers and the introduction of innovative medical technologies, one of the activities of the National Medical Research Center for Hematology (Center) is the analysis of the staffi ng of medical organizations (MO) of the constituent entities of the Russian Federation (RF) by hematologists. Aim — to analyze the dynamics of staffi ng by hematologists of MO in the RF. Materials and methods. Data from the Federal State Statistics Service (Rosstat) — Federal Statistical Observation Form No. 30 “Information about a medical organization” of the constituent entities of the Russian Federation for 2012–2020, reference books of the Central Research Institute of Organization and Informatization Health of the Russian Ministry of Health in the Russian Federation, information obtained from the results of on-site events of the National Medical Research Center for Hematology, including expert assessments were used. Results. The hematological service is organized in all subjects of the RF, with the exception of the Chukotka and Nenets Autonomous Okrug, Republic of Kalmykia and Altai, as well as the Jewish Autonomous Region. As of December 31, 2021, 1,594 hematologists work in the constituent entities of the RF, of which 460 specialists are in outpatient care and 1133 specialists in hospital settings. Analysis of the availability of full-time positions of hematologists per 10,000 populations in the Russian Federation in dynamics for 2012–2020 revealed fl uctuations in the values of this indicator from 0.06 to 0.17. The largest “failure” in the provision of hematologists occurred in 2014 in almost all federal districts (FD) of the Russian Federation. Only the Urals FD maintains the stability of the indicator of availability of these specialists. Over the past 3 years, there has been an increase in the number of full-time positions of hematologists, while the staffi ng of individuals reduced due to the lack (increase) of new employees and slightly offset by an increase in the coeffi cient of internal part-time work. Thus, the highest combination coeffi cient was noted in 2020 in the Ural (1.49) and Siberian (1.45) FD, the lowest in the North-Western FD (1.09). In accordance with the legal act regulating the activities of the hematology service, the standard for calculating the positions of outpatient hematologists is 1 doctor per 200 thousand of the population, however, the provision of full-time positions for the outpatient stage of care remains not achieved (2021 — 0.92 per 200 thousand); at least 731 doctors are needed against the existing 456 specialists. The staffi ng standard of the department of hematology corresponds to one medical position per 10 beds. Compliance with regulations regarding the formation of the staffi ng table of the inpatient unit was noted in 95% of the constituent entities of the Russian Federation. Conclusion. The issues of personnel shortage of hematologists are relevant. The shortage of hematologists in the Russian Federation indicates the lack of attractiveness of remuneration and indicates the need for management decisions to be made by the Government of the Russian Federation and executive authorities of the constituent entities of the Russian Federation aimed at developing mechanisms for maintaining the human resource of hematologists in the healthcare system.

Preclinical studies showed synergic anti-tumor activity of Rituximab and Fludarabin. Comparison of efficacy of FC with FCR regimens administered in first line therapy and their influence on disease-free and overall survival in patients with B-cell lymphocytic leukemia were the main goals of this retrospective study. It has been demonstrated that inclusion of Rituximab into the FC regimen improves outcome of patients with B-cell lymphocytic leukemia without significant increase of toxicity.

Introduction. The hematology service registration system describes actual indicators of hematology service infrastructure and target objects of both assigned and affiliated organizations of Russian Federation regions along with its correlations. This system data base makes it possible to collect, save, and analyze information, creating a data storage library about all current existing resources and taking into account concrete, specific conditions of specialized and high-tech hematological medical assistance organizations at the local levels and formed quality and availability optimization proposals.Aim — description and justification of the need to create a unified, complex, available to all users, informational reference system with the possibility of up-to-date maintenance and accounting that allows for the keep and control of the regional characteristics and hematology service indicators of the Russian Federation.General findings. The creation of and development of the hematology service registration system began in 2018, and work on the project continues. Four main phases were selected as the key stages of the hematology service pasportisation: analyses of the current data, verification of information, creation of a user-friendly tool, system updating. Objects to monitor: medical key and related institutions, universities, affiliated organizations, laboratory service. The data working stages: data collection, manual updating, package uploading. The information sources: official websites, data high-tech medical treatment web portal, web portals of the public health authorities, Compulsory Medical Insurance Fund website, The Unified Data Health Care System, license register of the Federal Service for Healthcare Surveillance, data of the Federal State Statistics Service, official documents of Ministry of Public Health. Based on the developed checklists and forms for entering additional information for specialists of the subjects of the Russian Federation, a reference book of the Ministry of Defense (Excel file format) was created. However, in the course of further remote interaction and conducting field events in the regions of the Russian Federation during 2019–2020 new data needs for evaluating hematology services were determined. The increase of additional data inputs and its structure complication became the main reasons for further developing a new platform design concept and data conversion in database framework of the hematology service registration system (Access file format). The current objectives are as follows: authentication of the internal objects identifiers, implementation of the relational database codifier, modification of cartographic display and objects routing. The hematology service registration system contains data both for the key infrastructure nodes of Russian Federation hematology service and correlations within routing of all key system objects. Based on the positive results, the hematology service registration system is planned to be used by experts of specialized medical organizations, regional executive authorities on public health and professional communities, who will be able to accumulate all changes and indicators in dynamics within one system. The expected result is to provide the Ministry of Defense of the Russian Federation regions with methodological and informational support in specialized and high-tech medical care administration.

Introduction . The advent of tyrosine kinase inhibitors (TKIs) in clinical practice drastically improved prognosis in patients with chronic myeloid leukaemia (CML). Adverse events of the TKI therapy and its high financial burden warrant the trend to gradually abandon this treatment. Aim . To assess the results of CML patient monitoring after the withdrawal of TKI therapy. Patients and methods . This prospective study included 98 chronic phase CML patients satisfying the criteria: any receiving of TKI therapy for ≥3 years; deep molecular response (DMR, BCR-ABL ≤ 0.01 % IS) during ≥ 2 years. The withdrawal was followed by quantitative BCR-ABL estimation performed monthly for the first 6 months of the survey, bimonthly for 1 year and every 3 months from the second year onwards. Therapy was resumed at a loss of major molecular response (MMR, BCR-ABL ≥ 0.1 % IS). Results . The MMR loss upon the TKI withdrawal was observed in 48 (49 %) patients. Survival without MMR loss was 52 % past 24 months since withdrawal, with a median of 35 months (23–52). The duration of therapy, MR and the MR depth at the time of withdrawal significantly correlated with a conserved post-therapy MMR. Gender, age, a Sokal risk group, type and line of TKI therapy at withdrawal, and imatinib resistance in history were not observed to significantly impact molecular relapse-free remission. MMR was recovered in all 48 patients with TKI therapy resumed in molecular relapse. In 65 % of the patients, adverse therapy events observed during treatment completely resolved by 6 months of post-therapy monitoring. Musculoskeletal pain (withdrawal syndrome, WS) was reported in 42 % patients in the post-therapeutic period, which did not lead to TKI resumption. The WS development correlated with an elder age and longer therapy prior to withdrawal. Conclusion . Molecular relapse-free survival in CML patients with treatment-free remission (TFR) is comparable to other published evidence. Monitoring safety during TFR is attested by the lack of disease progression and MMR recovery upon TKI resumption in all patients.

Aim. Based on our own materials to characterize the clinical manifestations of hypereosinophilic states distinguishing between reactive eosinophilia (RE), clonal myeloproliferative neoplasms with eosinophilia (MPN-eo), and myeloproliferative variant of hypereosinophilic syndrome (MP-HES); to evaluate treatment results. Materials & Methods. The trial included 188 patients with primary HES (132 men and 56 women, aged 19-72 years) having been followed-up at the National Research Center for Hematology since 2001. The main entry criteria were blood eosinophilia > 1.5 x 109/L and clinical symptoms resulting sometimes from hypereosinophilia. All patients received complete physical examination, immunomorphological, standard cytogenetic, and molecular genetic testing. Treatment was provided to 73 patients (63 men and 10 women) including those with MPN-eo PDGFRA+ (п = 39), PDGFRB+ (п = 2), FGFR1+ (п = 1), chronic eosinophilic leukemia not otherwise specified (п = 8), systemic mastocytosis (п = 1), and MP-HES (п = 22). Complete hematological response (CHR) was the criterion for treatment efficacy. In the MPN-eo PDGFRA+ and PDGFRB+ groups molecular response (MR) rate was also estimated in cases of imatinib treatment. MR was considered as no expression of the FIP1L1-PDGFRA and ETV6-PDGFRB transcripts in RT-PCR. Results. The trial yielded the cause of eosinophilia in 117 (62.2 %) out of 188 patients. RE was diagnosed in 60 (32 %) out of 117 patients, various types of clonal MPNs were reported in 57 (30 %) patients. In 71 (38 %) out of 188 patients HES was still present at the first trial stages. Later within this group MP-HES was identified in 22 (30.9 %) out of 71 patients. Among imatinib recipients CHR was achieved in 37 (90 %) out of 41 patients within 1-3 months: in 36 patients with MPN-eo FIP1L1-PDGFRA+ and in 1 patient with MPN-eo ETV6-PDGFRB+. MR was achieved in 88 % of cases. In the absence of molecular markers characteristic of MPN-eo CHR was achieved in 26 % of cases. Among the recipients of treatments other than imatinib nobody achieved CHR. Conclusion. The diagnosis approach in patients with HES should be complex and individualized. Development and enhancement of molecular genetic diagnostic techniques are regarded as ones of the highest priority areas in modern hematology. The use of imatinib mesylate in MPN-eo therapy commonly results in long-term hematological and molecular remissions. On achieving CHR to imatinib treatment of patients without molecular markers characteristic of MPN-eo early use of this drug (or other tyrosine kinase inhibitors) can be recommended in acute forms of HES.

Myeloproliferative disease associated with FGFR1 rearrangement (8p11), which is included in the 2008 WHO Classification of Myeloid Neoplasms, is a rare and extremely aggressive abnormality. The paper describes a clinical case of a 39-year-old female patient who was detected to have leukocytosis (as high as 47.2·109/l), absolute eosinophilia (as high as 3.1·109/l), and enlarged peripheral lymph nodes during her visit to a doctor. The bone marrow (BM) showed the changes typically encountered in myeloproliferative disease with eosinophilia. The patient was found to have t(8;13)(p11;q12) translocation associated with the rearrangement of the FGFR1 gene located at the 8p11 locus. Molecular and cytogenetic examinations failed to reveal BCR-ABL chimeric transcript, Jak2 V617F mutation, and deletions and translocations involving PDGFRA (4q12) and PDGFRB (5q32-33). The similar changes in the karyotype were also found in the lymph node cells. The undertaken treatment with hydroxyurea and the tyrosine kinase inhibitor dasatinib turned out to be ineffective. The patient underwent allogeneic BM transplantation from a HLA-identical sibling. Graft rejection occurred 6 months later. Allogeneic BM transplantation from the same donor (100% donor chimerism; FGFR1/8р11 translocation was not detected), which was complicated by the development of chronic graft-versus-host reaction, was performed again in March 2015. The patient is being followed up and continues to receive immunosuppressive therapy.

The efficiency of repeated courses of antithymocytic globulin (ATG) and algorithm thereof in combination with long-term cyclosporin A (CsA) therapy were studied. The incidence and time course of the cell clone characteristic of paroxysmal nocturnal hemoglobinuria (PNH clone) were studied in patients with aplastic anemia (AA) at different stages of immunosuppressive therapy (IST). The therapeutic algorithm used in the study led to positive response in the majority (84.9%) of AA patients. Remission was attained in 76.7% responding patients, complete remission in 76.8% of these. The majority of patients (61.6%) responded to therapy after the first course of ATG. Clinical hematological improvement was attained in 52.8% patients after 3 months of therapy; after 6 months common response was recorded in 83.4% patients. This period (3-6 months after the beginning of IST) should be regarded, in cases without response to ATG course 1, as the optimal for ATG course 2. Course 2 of ATG led to positive response in 16 more patients, that is, 802% patients responded to therapy after two ATG courses. Patients with AA not responding to therapy after two courses of ATG 6-9 months after the beginning of treatment could be referred to the group of patients with refractory AA. Overall and uneventful 7-year survival of AA patients after combined 151 was 89% (95% Cl 83-96%) and 93% (95% Cl 88-97%), respectively. The PNH clone was detected before IST in 20 (61%) of 33 patients with AA. The median of PNH clone for granulocytes was 1.93% (0.1-99.5%). The clone emerged and persisted in 6 (46%) of 13 patients in whom it was detected before IST. All six patients responded to IST. Seventeen (85%) of 20 AA patients with PNH clone, detected before IST, responded to IST. In the remaining 3 (15%) patients the PNH clone reduced more than 5-fold, up to complete elimination. Of AA patients without PNH clone before therapy, 8 (61%) responded to therapy. Our results confirmed the probability of response to IST in AA patients with PNH clone. The results of combined IST in AA patients indicated high efficiency of the protocol including repeated ATG courses and Ionc CsA therapy.

Aim. To evaluate the effect of pathogen-inactivated platelet concentrates (PIPC) on posttransfusion platelet increments, hemorrhagic syndrome relief, and transfusion intervals.Subjects and methods. This prospective study included 29 hemoblastosis patients (13 women, 16 men), median age 38 years (20-66 years). Pathogens were inactivated by the photodynamic method using the Intecept system. Each patient received two PC transfusions: one PIPC transfusion and one control one. Posttransfusion platelet increments one hour and one day after PC transfusion, the course of hemorrhagic syndrome, and the time to next platelet transfusion were analyzed.Results. Pathogen inactivation with amotosalen and ultraviolet irradiation reduced posttransfusion platelet increments in recipients by 24% after one hour and by 29% after one day after PIPC transfusion versus control ones.Conclusion. The clinical efficiency of transfusions of amotosalen-induced PIPC was comparable with that of untreated platelet concentrates. Despite a reduction in post-transfusion platelet increment with the use of PIPC, this caused no significant increase in the frequency,of transfusions.

Aim. To make differential diagnosis of thymic hyperplasia and mediastinal tumor after chemotherapy (CT) in patients with Hodgkin's disease (HD). Material and methods. The examination of 182 HD patients aged 16-71 years (median 28 years) included chest x-ray computed tomography (XCT) at baseline, during treatment, each 3 months, ultrasound investigation of the chest and abdominal cavity. All the patients received 6-8 courses of the treatment according to the program BEACOPP-14 followed by radiotherapy on the residual tumor in 137 patients, or not followed in 45 patients. Results. Soft tissue tumor in the anterior mediastinum was detected in 14 (31%) from 45 unirradiated patients (age 19-31 years, median 24 years) 1 to 10 months (median 3.5 months) after chemotherapy. The analysis of the data of ultrasound investigation and tomography identified a mediastinal lesion as thymic hyperplasia. The patients are now in remission with follow-up median 21 months (13-36 months). No recurrence was registered. Conclusion. Young HD patients with unirradiated mediastinum develop thymic hyperplasia in 31% cases within one year after chemotherapy. In view of this, detection of the lesion in the anterior mediastinum after CT demands complex examination for differential diagnosis of thymic hyperplasia with tumor recurrence to avoid unwanted intensification of the treatment.

Results of treating a group of patients with T-cell skin lymphoma are presented in article. The diagnosis mycosis fungoides (MF) established in 48 patients (24 men and 24 women). The median of age 52 years (26-77 years). The diagnosis syndrome Sezary (SS) established in 20 patients (men 12, women 8). The median of age was 61 year (23-87 years). Half of patients have arrived under supervision of our clinic with III-IV stages of disease. Cytostatic therapy does not lead to radical treatment. The positive result of treatment consists in reception of complete or partial remission or stabilization of illness within several months or years and improvement of quality of life of patients. The median follow up of patients with MF makes 85 months, at patients with SS 60 months. The median of survives of patients with MF makes 199.2 months, at patients with SS 75.3 months. The carried out researches in patients of the presented group have shown, that early application of intensive chemotherapy is irrational, as quite often leads to septic complications Alpha interferon (IFN-а) is one of the most active biological agents in therapy MF and SS, especially in the first stages of disease. IFN-а can be applied as monotherapy or in a combination to beam therapy, retinoids and cytostatics.

This paper presents the almost 20-year experience gained at the first in Russia hospital of day stay for hematology patients. Specific features of its work, criteria of efficiency, and problems of organization are analyzed. Improvement of the activities of the hospital of day stay are discussed in connection with increasing availability of high-technology specialized medical care. Prospects for development of specialized care of hematological patients, rendered in an outpatient setting, are discussed.

AIM:To study prognostic factors in previously untreated patients receiving FC regimen (fludarabine plus cyclophosphamide).MATERIAL AND METHODS:We conducted a retrospective analysis of B-CLL patients observed in Hematology Research Center of Russia (Moscow) and Faculty Therapy Clinic of St. Petersburg State Medical University (St. Petersburg). All patients received FC regimen as a first line treatment (fludarabine 50 mg plus cyclophosphamide 250 mg/m2 for 3 days intravenously, repeated every 28 days).RESULTS:54 patients were included into the study. The median age was 57.5 yrs (range 40-78 yrs). There were 38 males and 16 females. Before the treatment 22% patients had Binet stage A, 41%--stage B and 37%--stage C. 62% patients had unmutated subtype of B-CLL and 38% mutated subtype. 12 patients (22%) received less than 4 cycles of chemotherapy. In 8 patients (15%) there were significant delays between cycles (more than 2 months). In the whole cohort the median overall survival calculated from the time of treatment initiation was 57.4 months, the median progression free survival--24 months, and the median relapse free survival--27 moths. Mutational status of immunoglobulin variable region genes significantly influenced survival. In patients with unmutated subtype the median progression free survival was 23.6 months, while in patients with mutated subset it was not reached: 75% survival at 22.7 months (p = 0.027). Difference in progression free survival by stages (A versus B+C, A+B versus C) was not significant.CONCLUSION:Our data show that mutational status of immunoglobulin variable region genes remains a significant prognostic factor in patients receiving combined therapy with cyclophosphamide and fludarabine.