[Multiple primary tumor of hematopoietic tissue: myeloid sarcoma in combination with mantle cell lymphoma. Case report].

The prevalence of multiple primary tumors has significantly increased last time. The question of choosing the optimal tactics of therapy today not fully resolved. Particular interest is the simultaneous detection of two neoplasms of similar origin in one study biopsy material. This publication presents a case of simultaneous diagnosis of myeloid sarcoma and mantle cell lymphoma in a 65-year-old patient, which required use of two different chemotherapy protocols. This example shows the need to use an extended diagnostic approach at all stages of the therapy, which allows choosing right tactics of therapy and achieving complete remission of two neoplasms.

[Extracorporeal cytokine removal in chimeric antigen receptor T-cell therapy associated cytokine release syndrome in patient with acute lymphoblastic leukemia. Case report].

Сytokine release syndrome is the common complication of CAR-T therapy. We report a case of patient with B-cell acute lymphoblastic leukemia developing сytokine release syndrome with shock and multiple organ failure and requiring cytokine removal and hemodiafiltration. Remission of the disease was achieved after CAR-T therapy.

[Li-Fraumeni syndrome in adult patients with acute lymphoblastic leukemia].

BACKGROUND: LiFraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary disorder that is characterized by an increased risk for certain types of cancer, acute lymphoblastic leukemia (ALL), particularly. Germline TP53 mutations are associated with LFS. Genetic counseling and follow-up is essential for patients with LFS and their relatives. Special therapeutic approaches are needed for treatment of oncological disease in these patients. The article presents a series of clinical cases of patients with ALL and SLF, considers general issues of diagnosis and treatment of adult patients with this hereditary genetic syndrome. AIM: Describe clinical observations of patients with acute lymphoblastic leukemia (ALL) and LFS and consider general issues of diagnosis and treatment of adult patients with LFS and ALL. MATERIALS AND METHODS: TP53 gene mutations were screened using Sanger sequencing in 180 de novo patients with Ph-negative (B- and T-cell) and Ph-positive ALL treated by Russian multicenter protocols (ALL-2009, ALL-2012, ALL-2016) at the National Research Center for Hematology, Moscow, Russia, and at the hematology departments of regional clinics of Russia (multicenter study participants). RESULTS: TP53 gene mutations were found in 7.8% (n=14) of de novo ALL patients. In patients, whose biological material was available TP53 gene mutational status was determined in non-tumor cells (bone marrow and peripheral blood during remission, bone marrow samples after allogeneic hematopoietic stem cells transplantation and in tissue of non-hematopoietic origin) for discriminating germline mutations. The analysis included 5 patients (out of 14 with TP53 mutations), whose non-tumor biological material was available for research. Germline status was confirmed in 4 out of 5 B-cell ALL (n=3), T-cell ALL (n=1) investigated patients. CONCLUSION: Practical value of the research is the observation that the greater part of TP53 gene mutations in patients with Ph-negative B-cell ALL are germinal and associated with LFS.

[A case report of familial dyskeratosis congenital. Case report].

Dyskeratosis congenita (DC) is a hereditary syndrome of bone marrow failure, which develops because of telomeres defects and combines with cancer predisposition. Its classical clinical features are skin pigmentation, nail dystrophy, oral leukoplakia (skin-mucosa triad). The goal is to describe the algorithm of diagnosis, clinical specificities of DC and specific treatment for cases of DC in one family. The present report includes descriptions of diagnosis and treatment of family members diagnosed for the first time as having a DC. The report shows an importance of all diagnostic stages: from a medical history and clinical picture to an application of modern high-tech diagnostic methods (flow-FISH, NGS). The report underlines an importance of diagnosis of all family members for excluding an asymptomatic form after a case of DC has been already detected in that family. A high frequency of a toxicity and secondary neoplasia makes it necessary to realize an individual approach at treatment of each patient with DC (the earliest start of androgen treatment, prompt decision of implementation of allogenic hematopoietic stem cell transplantation). The knowledge of pathogenesis, clinical features and principles of diagnosis and therapy of this disease is relevant to pediatricians and hematologists.

[Development of program therapy for patients with acute myeloid leukemia under the age of 60 years, based on the principles of differentiated effects].

AIM: To analyze the results of treatment in patients with acute myeloid leukemia (AML) within protocols AML-17 and modified AML-17 (mOML-17) as part of two consecutive pilot studies in order to develop the best treatment strategy for AML patients aged below 60 years. MATERIALS AND METHODS: The study included 89 AML patients who were aged below 60 years and received treatment within the AML-17 and mOML-17 protocols. Cytogenetic and molecular genetic studies were performed in all patients. The presence of mutations in the FLT3, NPM1, CEBPa genes was assessed by fragment analysis. 35 patients underwent a study for mutTP53, mutRUNX1 using next generation sequencing (NGS). The minimum residual population of tumor cells was evaluated by multicolor flow cytometry. Statistical analysis was performed using the procedures of the SAS 9.3 package. RESULTS: Complete remission (CR) was achieved in 89.7% of patients treated with intensive chemotherapy (CT) courses and in 52.4% of patients treated with low-dose CT courses. 8.8% of intensively treated patients were refractory to therapy, and 38% did not respond to low-dose exposure. The early mortality rate was 3%. The overall survival and disease-free 3-year survival for patients included in 2 consecutive studies was were 60% and 67%, respectively. The level of minimal residual disease (MRD) after the first course of induction CT was an important prognostic indicator. The three-year relapse-free survival for patients in whom CR was achieved after the first course of induction CT and in whom MRD was not detected (MRD-negative status was obtained) was 90% compared to 43% for patients who were MRD positive after the first course of induction CT (p=0.00001). CONCLUSION: The key factor that significantly affects the long-term results of therapy is the rate of MRD after the first course of induction CT.

[Immunosupressive therapy of aplastic anemia patients: successes and failures (single center experiment 2007-2016)].

Treatment programs for patients with acquired aplastic anemia include two main therapeutic options: allogeneic bone marrow transplantation and combined immunosuppressive therapy (IST). However, combined IST remains the method of choice for most adult AA patients. This study included 120 AA patients who received IST at the National Research Center for Hematology in 20072016. The analysis was applied to 120 patients. Median age was 25 (1765) years, M/F: 66/54, SAA/NSAA: 66%/34%. Effectiveness of IST was carried out in 120 patients with AA. This group did not include 8 SAA patients who died during the first 3 months from the start of treatment from severe infectious complications (early deaths 6.2%) and 2 AA patients who dropped out of surveillance. The observation time was 55 (6120) months. Paroxysmal nocturnal hemoglobinuria (PNH clone) was detected in 67% of AA patients. The median PNH clone size (granulocytes) was 2.5 (0.0199.5)%. The treatment was according to the classical protocol of combined IST: horse antithymocytic globulin and cyclosporin A. Most of patients (87%) responded to combined immunosuppressive therapy. To achieve a positive response, it was sufficient to conduct one course of ATG to 64% of patients, two courses of ATG 24% of patients and 2% of patients responded only after the third course of ATG. A positive response after the first course was obtained in 64% of patients included in the analysis. Most of the responding patients (93%) achieve a positive response after 36 months from the start of treatment. Therefore, the 3rd6th months after the first course of ATG in the absence of an answer to the first line of therapy can be considered the optimal time for the second course of ATG. This tactic allows to get an answer in another 58% of patients who did not respond to the first course of ATG. The probability of an overall 10-year survival rate was 90% (95% confidence interval 83.696.2).

[Role of the intensive care in treatment of patients with acute myeloid leukemia].

AIM: Remission induction can be associate, with the life threatening complications and transfer to ICU of de novo acute myeloid leukemia (AML) patients (pts). We evaluate influence of transfer to ICU and life threatening complication on early mortality and long - tram survival of de novo AML pts. MATERIALS AND METHODS: Retrospective study. All de novo AML pts younger than 60 years old admitted in the National Research Center for Hematology from 2013 to 2016 years were enrolled in the study. Patients were divided into 2 groups: pts who were required ICU admission during remission induction (ICU-pts) and pts who did not require ICU admission and received chemotherapy only in hematology ward (non-ICU pts). The reasons for ICU admissions and results of life support were analyzed. Overall survival (OS) were assessed by the Kaplan-Meier method, long rank value p.

Structure and significance of cytogenetic abnormalities in adult patients with Ph-negative acute lymphoblastic leukemia.

AIM: To evaluate occurrence, variety, structural peculiarities and prognostic meaning of cytogenetic abnormalities in adult patients with Ph-negative acute lymphoblastic leukemia (ALL) receiving therapy according to ALL-2009 protocol. MATERIALS AND METHODS: The study included 115 adult patients with firstly diagnosed Ph-negative ALL: 58 male and 57 female aged from 15 to 61 years (mean age 26.5 years), who underwent treatment from September 2009 to September 2015 in National Medical Research Center for Hematology MH RF (n=101) and in hematology departments of regional hospitals (n=14). All patients received therapy of ALL-2009 protocol (ClinicalTrials.gov, NCT01193933). The median follow-up was 24.5 months (0.2-94.4 months). As a part of the study results of a standard cytogenetic assay (SCA) were analyzed and fluorescence hybridization in situ (FISH) with the use of DNA-probes was performed on archived biological material for structural changes in gene locuses MLL/t(11q23), с-MYC/t(8q24), TP53/ deletion 17p13, CDKN2A/ deletion 9p21, translocation t(1;19)/E2A-PBX1 и t(12;21)/ETV6-RUNX1; iAMP21 identification. RESULTS: Karyotype was defined using SCA in 86% of patients. Normal karyotype was found in 48.5% of them, chromosome aberrations in 51.5% (structural changes were found in 19.2%, hyperploidy in 27.2%, and hypoploidy in 5.1%). In 17.2% of patients complex karyotype abnormalities were found. With the use of FISH technique aberrations were found in 67% of patients: 9p21/CDKN2A deletion in 24.3%, MLL/t(11q23) gene abnormalities in 7.8%, 17p13/TP53 deletion in 5.2%, abnormalities of c-MYC/t(8q24) in 1.7%, t(1;19)/E2A-PBX1 in 0.8%, and iAMP21 in 0.8%, other abnormalities (additional signals/absence of signals from gene locuses) in 26.4%, t(12;21)/ETV6-RUNX1 was not found. FISH technique use in addition to SCA allows to increase aberrant karyotype location from 51.5 to 67%. A statistically significant correlation of 9p21/CDKN2A deletion with high serum lactate dehydrogenase activity (p=0.02); MLL/t(11q23) gene abnormalities - with leucocytosis and high blast cells level in blood (p=0.0016), hyperploidy - with normal leukocyte count (p=0.02) was shown. In groups with different cytogenetic abnormalities no statistically significant differences of treatment with ALL-2009 protocol were found (in terms of complete remission, early mortality and treatment resistance). When connection of cytogenetic abnormalities and their combinations with long-term results were analyzed according to ALL-2009 protocol, only two characteristics - MLL/t(11q23) and c MYC/t(8q24) gene abnormalities had a statistically significant influence on disease-free survival (HR - 176.9; p<0.0001) and chance of recurrence (HR - 6.4; p=0.02). CONCLUSION: Adverse prognostic factors in terms of therapeutic management provided in ALL-2009 protocol were MLL/t(11q23) and с-MYC/t(8q24) genes abnormalities. CDKN2A/9p21 and TP53/17p13 genes deletions, quantative and complex karyotype abnormalities were not prognostic factors in adult patients with Ph-negative ALL in ALL-2009 protocol use.

Diagnostics and treatment challenges of Ph-like acute lymphoblastic leukemia: a description of 3 clinical cases.

B-cell acute lymphoblastic leukemia (B-ALL) is a diverse group of malignant blood disorders both with regard to the biological properties of the tumor and to therapeutic approaches. Immunophenotyping, molecular genetic techniques, whole-genome sequencing characterize B-ALL as a very diverse group for sensitivity to chemotherapy and prognosis. We present three clinical cases of patients with B-ALL and expected good response to standard therapy, in whom standard protocol treatment failured: refractoriness, persistence of minimal residual disease (MRD), and progression (MRD increase). The remission in these patients was achieved after chemotherapy change to immunological targeted therapy. Nowadays a unified therapeutic approach to all primary patients of the B-ALL is considered generally outdated. Great efforts are carrying out to develop molecular genetic classifications. The molecular dissection of subtypes of B-ALL goes on, and new protocols for selective treatment with targeting are clearly outlined for each subtype of B-ALL.

Results of program acute myeloid leukemia therapy use in National Medical Research Center for Hematology of the Ministry of Health of Russian Federation.

AIM: To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF. MATERIALS AND METHODS: Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses "7+3" with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients. RESULTS: The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 и 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%. CONCLUSION: Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR.

[Absolute numbers of peripheral blood CD34+ hematopoietic stem cells prior to a leukapheresis procedure as a parameter predicting the efficiency of stem cell collection]. / Absoliutnoe kolichestvo gemopoéticheskikh stvolovykh kletok CD34+ v perifericheskoi krovi pered protseduroi leikafereza kak parametr, prognoziruiushchii éffektivnost' sbora stvolovykh kletok.

AIM: To identify a parameter predicting a collection of at least 2·106 CD34+ hematopoietic stem cells (HSC)/kg body weight per leukapheresis (LA) procedure. SUBJECTS AND METHODS: The investigation included 189 patients with hematological malignancies and 3 HSC donors, who underwent mobilization of stem cells with their subsequent collection by LA. Absolute numbers of peripheral blood leukocytes and CD34+ cells before a LA procedure, as well as a number of CD34+ cells/kg body weight (BW) in the LA product stored on the same day were determined in each patient (donor). RESULTS: There was no correlation between the number of leukocytes and that of stored CD34+ cells/kg BW. There was a close correlation between the count of peripheral blood CD34+ cells prior to LA and that of collected CD34+ cells calculated with reference to kg BW. CONCLUSION: The optimal absolute blood CD34+ cell count was estimated to 20 per µl, at which a LA procedure makes it possible to collect 2·106 or more CD34+ cells/kg BW.

[EBV-positive central nervous system lymphoproliferative disease associated with immunosuppression after organ transplantation: Long-term remission without chemotherapy]. / Limfoproliferativnoe EBV-pozitivnoe zabolevanie s porazheniem tsentral'noi nervnoi sistemy, assotsiirovannoe s immunosupressiei posle organnoi transplantatsii: dlitel'naia remissiia posle khimioterapevticheskogo lecheniia.

Primary central nervous system (CNS) lymphomas account for 13-20% of the posttransplant lymphoproliferative disorders (PTLD) and rank among the most aggressive conditions. Reduction of immunosuppressive therapy should be mandatory to treat PTLD, but this is rarely used as the only therapy option. Chemotherapy regimens for PTLD involving the CNS most commonly include high-dose rituximab and high-dose methotrexate and/or cytarabine. The efficiency only of discontinuation of immunosuppressive therapy for PTLD does not exceed 5-10%, but there are no literature data on its efficiency for PTLD involving the CNS. The paper describes a clinical case of achieving long-term remission in a female patient with Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma involving the central nervous system, associated with immunosuppression after kidney transplantation from a related donor, in the absence of chemotherapy during immunosuppressive therapy discontinuation and transplantectomy.

[Impact of current approaches to laboratory screening of donated blood and its components on hepatitis B virus infection in patients with blood system diseases]. / Vliianie sovremennykh podkhodov k laboratornomu obsledovaniiu donorov krovi i ee komponentov na infitsirovannost' virusom gepatita V u bol'nykh s zabolevaniiami sistemy krovi.

AIM: To evaluate the detection rate of markers for hepatitis B virus (HBV) in the blood samples taken from patients with blood system diseases, by applying the current approaches to examining donated blood and its components for markers of viral infections. MATERIAL AND METHODS: The investigation included blood samples from patients with blood system diseases (n=364) and donors (n=5,011). The results of laboratory screening of donated blood samples (n=13,081) were retrospectively analyzed. Commercial kits of reagents were used for immunochemical assay and polymerase chain reaction. RESULTS: Patients with blood system diseases were recorded to have markers of active HBV infection in 12.6% of cases, anti-HBc in 31.3%, and anti-HBs in 37.6%. A retrospective analysis of the results of screening donated blood samples showed the presence of markers for active HBV infection in 0.28% of cases. A prospective examination of blood donors revealed markers of HBV infection in 4.83% of cases, including those of active forms in 0.54% and anti-HBc in 4.79%. The markers of active HBV infection in donors were only anti-HBc IgM in 0.42% of cases. The blood samples from donors with an anti-HBs titer of >200 mIU/ml contained anti-HBc IgM in 10.5%. CONCLUSION: In the last 5-7 years, the detection rate of markers of HBV infection in the blood samples of patients with blood system diseases have remained at a high level. Screening for decreed markers fails to identify people with inapparent infections among the donors. Even high anti-HBs concentrations in the donated blood may be a risk for HBV transmission by transfusion to a recipient.

[Adult B-cell acute lymphoblastic leukemias: Conclusions of the Russian prospective multicenter study ALL-2009]. / Ostrye V-limfoblastnye leikozy vzroslykh: vyvody iz Rossiiskogo prospektivnogo mnogotsentrovogo issledovaniia OLL-2009.

AIM: To analyze the efficiency and reproducibility of the ALL-2009 protocol within the Russian prospective multicenter study based on different principles of cytostatic effects (non-intensive, but continuous cytotoxic treatment and a small number of allogeneic hematopoietic stem cells). SUBJECTS AND METHODS: The ALL-2009 (NCT01193933) study conducted in April 2009 to December 2016 included 194 patients (95 males and 99 females) aged 15 to 55 years (median age 28 years) with Ph-negative B-cell acute lymphoblastic leukemia (ALL). There was early pre-B-cell ALL in 54 patients, common ALL in 101, pre-B ALL in 39, initial leukocytosis in 9.4·109/l (0.4-899.0), lactate dehydrogenase in 901 IU (31-13 059), an initial central nervous system lesion in 17 (8.7%), mediastinal injury in 3 (1.5%), and splenomegaly in 111 (57.2%). The results of standard cytogenetic analysis are known in 113 (60.4%) patients. Normal karyotypes were detected in 49 (54.5%) out of the patients; t(4;11) in 9 (5.4%), t(1;19) in 2 (1.2%), and other karyotypic abnormalities in 53 (46.9%). Thirteen (7.8%) patients underwent allogeneic hematopoietic stem cell transplantation in first complete remission (CR); their proportion did not differ in the federal and regional centers. RESULTS: The frequency of CR achievement was the same in the federal and regional centers and generally amounted to 87.5%. Early (8.8%) and CR (9.6%) mortality rates remained high despite the low aggressiveness of cytotoxic action, necessitating the improvement of auxiliary treatment. The five-year overall survival (OS) rates vary considerably in the federal and regional centers (72.6 and 43.8%), the relapse-free survival (RFS) (70.2 and 53.4%) and recurrence risk (23.1 and 36.5%) are comparable. This suggests that the non-intensive, but continuous exposure principle built in the ALL-2009 protocol makes it possible to reproduce the envisaged treatment program and to achieve satisfactory results. CONCLUSION: The ALL-2009 protocol allows both the federal and regional centers to obtain the long-term results comparable with those of current foreign studies: OS (54.2%), RFS (56.5%); and relapse risk (35.4%). Multivariate analysis has identified age (over 30 years), initial leukocytosis (30·109/l and more) and t(4;11) among the main clinical prognostic factors. Gene mutation detection evaluated in a small number of patients (8/36) is not a poor prognostic sign. There is a need for further investigations with centralized evaluation of the mutation status of leukemic cells and the clearance of minimal residual disease.

[Diffuse large B-cell lymphoma with monoclonal immunoglobulin secretion]. / Diffuznaya V-krupnokletochnaya limfoma s monoklonal'noi sekretsiei immunoglobulinov.

AIM: to provide the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) with monoclonal immunoglobulin secretion and to evaluate the efficiency of intensified mNHL-BFM-90 or R-DA-EPOCH/R-HMA therapy programs in patients with Ig-secreting DLBCL. SUBJECTS AND METHODS: A clinical trial was conducted in 93 patients with newly diagnosed DLBCL, among whom 21 (22.6%) were found to have monoclonal immunoglobulin secretion. RESULTS: Ig-secreting DLBCL is shown to be characterized by bone marrow involvement (p<0.001), as well as generalized injury (Ann Arbor Stage 4) and a high risk in accordance with the international prognostic index (p=0.001 and p=0.026, respectively). Analysis of overall and event-free survival rates has indicated that the patients have a poor prognosis versus those with non-Ig-secreting DLBCL and poor prognostic factors even when implementing intensified therapy programs, such as mNHL-BFM-90 or R-DA-EPOCH/R-HMA ones. CONCLUSION: The investigation has demonstrated that there is a high association of the secretion of monoclonal paraproteins with bone marrow involvement in DLBCL (p<0.001). The intensified therapy using the mNHL-BFM-90 and R-DA-EPOCH/R-HMA programs involving autologous hematopoietic stem cell transplantation also permits the patients with Ig-secreting DLBCL to achieve long-term sustained remissions in not all cases.

[Perianal infection in patients with hemoblastosis: Risk factors and possibilities of prevention]. / Perianal'naya infektsiya u bol'nykh gemoblastozami: faktory riska i vozmozhnosti profilaktiki.

AIM: to identify poor prognostic factors for perianal infection (PI) in patients with hemoblastosis and to define an effective tactic for preventive and therapeutic measures. SUBJECTS AND METHODS: The prospective study enrolled 72 patients (37 men and 35 women; mean age, 47 years) with hemoblastosis that was complicated by the development of one of the following forms of PI: abscess, infiltrate, multiple ulcers. Different clinical and laboratory characteristics of the patients were examined to identify risk factors for PI. The species-specific concordance of microorganisms isolated from the anus and blood in the development of PI was assessed to record the latter as a source of sepsis. Treatment policy was defined according to the clinical form of PI. RESULTS: Acute myeloid leukemias and lymphomas were the most common background diseases in 30 (41.7%) and 22 (30.6%) patients, respectively. During induction chemotherapy cycles, perianal tissue infection occurred twice more frequently (66%) than totally at the onset of hemoblastosis (13%) and after achievement of remission (during consolidation and maintenance therapy) (21%; Fisher's exact test; p=0.01). PI in agranulocytosis was more than twice as common as in its absence: 69.4% vs 30.6% (p=0.01) and was responsible for sepsis in 9 (18%) of 50 patients. The main source of perianal tissue infection in patients with granulocytopenia was anal fissures and fistulas and ulcers of the anal canal: 44 (88%) cases of the 50 cases. In PI as an abscess, the average white blood cell count was 5 times higher (p=0.01) than that in PI as an infiltrate (or multiple ulcers): 6.6·109/l and 1.2·109 g/l. Abscess formation was observed in 16 (22.2%) patients and an indication for surgical drain. The inflammatory infiltrate was found to develop in 48 (66.7%) patients; multiple ulcers were seen in 8 (11.1%); in this group, parenteral antimicrobial therapy proved to be effective in 36 (78%) patients. 29 patients were operated on for anal fissures and fistulas at intercycle intervals. After continuing CT, PI recurrences were observed in 4 (9.1%) patients. In the operated versus medically treated patients, the risk of complications associated with abnormalities in the perianal area during continued CT was 5 times statistically significantly lower (odds ratio=0.2; 95% confidence interval 0.1 to 0.5; p=0.04; Cochran-Mantel test). CONCLUSION: Induction CT cycles, the status of granulocytopenia, and the presence of infection sources in the anal canal as an anal fissure, skin ulcerations, or a fistula should be considered as independent statistically significant prognostic risk factors for PI. The number of granulocytes determines the form of inflammation, the course of infection, and the chance of developing sepsis. The effective prevention encompassing surgical treatment for anal canal diseases reduces the risk of septic complications and the number of paraproctitis recurrences, contributing to the implementation of a planned CT program in patients with hemoblastosis.

[Acute Ph-negative lymphoblastic leukemias in adults: Risk factors in the use of the ALL-2009 protocol]. / Ostrye Ph-negativnye limfoblastnye leikozy vzroslykh: faktory riska pri ispol'zovanii protokola OLL-2009.

AIM: to analyze well-known risk factors (RFs), such as age, immunophenotype, baseline leukocytosis, enhanced lactate dehydrogenase (LDH) activity, time to achieve complete remission, a risk group, and cytogenetic abnormalities) in patients with acute lymphoblastic leukemia (ALL) in the use of the ALL-2009 protocol. SUBJECTS AND METHODS: The protocol covered 298 patients (137 women (including 13 pregnant women) and 161 men) aged 15 to 55 years (median age 28 years) with Ph-negative ALL. The phenotype was unknown in 6 patients. Three (1%) were ascertained to have a biphenotypic variant. 182 (62.4%) patients were found to have B-cell ALL (early pre-B ALL (n=51); common ALL (n=92), and pre-B ALL (n=39); 107 (36.6%) patients had T-cell ALL (early T-ALL (n=56); thymic T-ALL (n=41), and mature T-ALL (n=10). According to the baseline clinical and laboratory parameters (leukocytosis of 30·109/l and more for B-ALL; and that of 100·109/l and more for T-ALL; phenotype В-I for B-ALL, phenotype Т-I-II-IV for T-ALL; LDH activity was more than twice the normal values; the presence of translocation t(4;11)), the high-risk group included most patients with B-ALL (n=110 (72.8%)) and T-ALL (n=76 (76%)). Thirty-five patients with T-ALL underwent autologous bone marrow transplantation (BMT). Allogeneic BMT was performed in 18 (7%) of the 258 patients who had undergone an induction phase. RESULTS: Five-year overall survival for all the patients included in the investigation was 59%; relapse-free survival was 65%, which was significantly different in the patients with B-ALL and in those with T-ALL: the overall survival rates were 53.3 and 67.5% (p=0.1); the relapse-free survival was 56 and 79% (p=0.005), respectively. Multivariate analysis including the well-known RFs demonstrated that the latter for T-ALL were of no independent prognostic value and only the patient's age was identified for B-ALL (p=0.013). CONCLUSION: A lower chemotherapeutic load and a small number of allogeneic BMTs did not affect total positive treatment results in adult patients with ALL, by complying with the principle achieving the continuity of cytostatic effects and by preserving the total cytostatic loading dose. The results of the Russian investigation casts some doubt on the necessity of using very intensive consolidation cycles and performing a large number of allogeneic BMTs in adult patients with ALL.

[The dynamics of paroxysmal nocturnal hemoglobinuria clone in patients with aplastic anemia in process of immune suppressive therapy].

The implementation of principles of highly sensitive flow cytometry into diagnostic of paroxysmal nocturnal hemoglobinuria increased rate of detection of paroxysmal nocturnal hemoglobinuria clone in patients with aplastic anemia already at early stages of diagnosis establishment (up to 79%). However, detection of paroxysmal nocturnal hemoglobinuria clone attracts interest not only from point of view of progression in % of patients with aplastic anemia). The occurrence of paroxysmal nocturnal hemoglobinuria clone in patients with aplastic anemia can be accompanied by hidden disorders of haemopoesis with increasing risk in conditions of proliferative stress. Hence, it is necessary to monitor the given clone during all period of observation. The study is a prospective investigation analyzing dynamics of paroxysmal nocturnal hemoglobinuria clone in process of immune suppressive therapy applied to 44 patients with aplastic anemia. The mentioned clone was initially detected in 59.6% of patients. The median of observation amounted to 27 (9-48) months. Depending on size of granulocytic paroxysmal nocturnal hemoglobinuria clone patients were allocated in four conditional groups: group I - from 0.01% to 0.99% (n=11); group II - from 1% to 9.99% (n=8); group III - from10% to 49.9% (n=4); group IV - from 50% and more (n=5). In the course of study the differently directed dynamics of paroxysmal nocturnal hemoglobinuria clone was revealed. In 3 out of 11 patients from group I median of paroxysmal nocturnal hemoglobinuria clone increased from minor values (less than 1%) to 3.55%; at that in one patient occurred total elimination of paroxysmal nocturnal hemoglobinuria clone to 12th month of observation. The noticeable unidirectional dynamics was established in patients of group III: already to 3d month of observation, simultaneously with becoming of remission, median of size of paroxysmal nocturnal hemoglobinuria clone in group diminished from 22.9% (18.39%-24.77%) to 5.6% (1.5%-6.7%). Among patients of groups II and IV paroxysmal nocturnal hemoglobinuria clone remained stable. The development of hemolytic form of paroxysmal nocturnal hemoglobinuria was observed in all patients of group IV i.e. in 18% of patients with aplastic anemia with primarily detected paroxysmal nocturnal hemoglobinuria clone. In the process of observation, in 37% of patients with aplastic anemia without primarily detected paroxysmal nocturnal hemoglobinuria clone its occurrence and persistence (median - 0.34% (0.1%-6.2%)) was noticed. According to the results of study, alteration of sizes of paroxysmal nocturnal hemoglobinuria clone or its occurrence develop in case of response to ISP and, most probably, depend on advantage of growth in the process of repair of normal (GPI positive) or clonal (GPI negative) hemopoiesis. To acquire more reliable conclusions will be possible through development of techniques of molecular diagnostic simultaneously with dynamic observation of course of disease in the given patients.

[Lung ultrasonography for the diagnosis of pneumonia in pregnant women with blood system tumors].

AIM: To estimate the informative value of ultrasonography (USG) in the diagnosis of lung injuries in pregnant women with blood system tumors. SUBJECTS AND METHODS: Lung ultrasound was performed in 5 pregnant patients with blood cancers. The women's age was 29-38 years; gestational age was 14-33 weeks. Four women had different types of acute leukemia; one had primary mediastinal large B-cell lymphoma. All the women received chemotherapy for blood cancer. When there were signs of lung injury, USG was conducted, the results of which necessitated therapy or bronchoalveolar lavage (BAL). RESULTS: Three patients developed acute respiratory failure; 2 of them required noninvasive ventilation. Based on the detection of consolidation with a dynamic air bronchogram and pleural effusion, the authors diagnosed bilateral pneumonia and alveolar-interstitial syndrome in 1 patient, right-sided pneumonia in 1, left-sided one in 1, and transfusion-related pulmonary edema in 1. Lung ultrasound did not verify the diagnosis of pneumonia in 1 patient. According to USG data, BAL procedures were performed in 2 patients; one of them was diagnosed as having Pneumocystis pneumonia; the other was found to have no pathogens in lavage fluid. Treatment resulted in clinical improvements and normalization of the lung ultrasound pattern in all the pregnant women. Later on, 4 women delivered via cesarean section done at 32-34 weeks' gestation and gave birth to healthy babies. One patient died from infectious complications after chemotherapy. CONCLUSION: Lung sound may be used to diagnose lung injury in pregnant women with blood cancers.

[Treatment in adult patients with acute myeloid leukemias and hyperleukocytosis at disease onset].

AIM: To evaluate the efficiency of the treatment policy for patients with acute myeloid leukemia (AML) and hyperleukocytosis (HL), which is aimed at preventing rapid hypercytolysis and massive tumor lysis (cytolysis) syndrome and/or at reducing the degree of the latter at the start of induction polychemotherapy. SUBJECTS AND METHODS: In 2010 to 2014, the Hematology Research Center, Ministry of Health of Russia, treated 92 patients with AML, out of them 18 patients were found to have white blood cell counts of 100 to 408-10(9)/1 (median, 130-10(9)/l) at the onset of the disease. All the examinees received cytoreductive therapy with hydroxyurea and, in presence of leukostasis and/or leukocytosis (≥150-10(9)/1), with leukocytapheresis. In case of reduced leukocytosis, plasmapheresis was carried out to prevent (treat) cytolysis. Daunorubicin was injected on days 3-5 of the 7+3 induction cycle. RESULTS: The signs of leukostases were detected in more than half of the 18 patients with higher white blood cell counts: 13 (72%) with lung injury, including 5 of them with signs of respiratory distress syndrome, 6 (27.8%) with neurological symptomatology, 7 (38.9%) with disseminated intravascular coagulation syndrome, including 1 with intracranial hemorrhage. Cytoreduction therapy with hydroxyurea (10 mg/kg/day) was performed 1-5 (median 2) days before initiating induction chemotherapy in 17 patients; 9 patients underwent 1-2 (median 2) leukocytapheresis sessions. Sixteen patients received 1-4 (median 2) plasmapheresis sessions prior to and within the first days of the 7+3 treatment regimen. Daunorubicin (60 mg/m2) was administered to 16 patients on days 5-7 of the 7+3 cycle and to 2 patients on days 3-5 of the cycle. There were no signs of severe cytolysis with the development of multiple organ dysfunction in any patient. 50% (9/18) achieved remission after the first 7+3 cycle and 7 more examinees did after the second cycle. Thus, the remission rate was 89%; early mortality was 5.5% (1/18), three-year overall and relapse-free survival rates were 50%. CONCLUSION: Adequate cytoreductive and accompanying therapies for AML with HL can virtually completely prevent massive tumor cytolysis syndrome and early mortality during the first days of induction chemotherapy.