[Adherence to treatment of hematological malignancies patients with anxiety and depression].

AIM: To establish the features of the influence of anxiety and depressive disorders on treatment adherence, as well as to clarify the factors associated with it in hematologic malignancies patients. MATERIALS AND METHODS: The study included 117 patients: 51 men and 66 women, aged 19 to 67 years, with Hodgkin's lymphoma - 88, acute lymphoblastic leukemia - 16 and aplastic anemia - 13 patients. Patients were examined by psychiatrist using the Brief Psychiatric Rating Scale, as well as some psychometric methods. RESULTS: Anxiety-depressive spectrum disorders were detected in 36 (40.9%) patients with Hodgkin's lymphoma and 8 (50%) with acute lymphoblastic leukemia, in the aplastic anemia group there were three (23.1%) of such patients. It was found that the average adherence to treatment was in 2/3 of patients, low and high - in the remaining 1/3 of patients. With medium and low adherence to treatment, the risk of adverse events increases by an average of 1.7 times. The adherence to treatment it is significantly higher in patients older than 45 years. Signs of depression that negatively correlated with adherence to treatment were pessimism and disruption of social ties. Adherence to treatment significantly positively correlates with the following types of attitudes towards the disease: anosognosic, hypochondriac and egocentric, and significantly negatively correlates with the following types of attitudes towards the disease: anxious, melancholic and dysphoric. CONCLUSION: Anxiety/depressive disorders contribute to reduced adherence of hematologic malignancies patients to treatment. Their correction and increased adherence should be carried out jointly by hematologists and mental health professionals.

[Pathomorphological and clinical characteristics of blastic plasmocytoid dendritic cell neoplasm. Case report].

The paper reveals the 5 cases date about blastic plasmacytoid dendritic cell neoplasm. The presented information demonstrates morphological, immunohistochemical data and clinical manifestations.

[Hairy cell leukemia and pregnancy]. / Volosatokletochnyi leikoz i beremennost'.

The paper presents experience in following up and treating hairy cell leukemia (HCL) during pregnancy. The combination of HCL and pregnancy was observed in 5 patients. The patients' median age was 35 years (range, 28-42 years). The diagnosis of HCL was based on a conventional examination protocol: clinical blood analysis with the morphological assessment of lymphocytes, a myelogram and trepanobiopsy, immunophenotypic analysis of lymphocytes or bone marrow (in all the patients), cytochemical determination of tartrate-resistant acid phosphatase in 3 patients, and identification of BRAFV600E mutation in 3 patients. Three pregnant women were treated for HCL in the postpartum period. In one patient with HCL, pregnancy was seen in remission after treatment with cladribine. In one patient with HCL detected at 11 weeks' gestation, interferon-α therapy during the second trimester of pregnancy was performed for increased cytopenia, which was followed by cladribine therapy after delivery. Pregnancy and delivery were uncomplicated in all the patients; 3 patients had vaginal delivery and 2 patients underwent cesarean section. All infants were healthy, with no developmental abnormalities during a follow-up period of 6-140 months (median 30 months). All the patients with HCL are currently in remission: 4 patients in first remission at a follow-up of 10 to 48 months (median 15 months) and one patient in second remission at a follow-up of 88 months. Possible observational tactics is possible when HCL is detected during pregnancy. Treatment of HCL during pregnancy is necessary in cases of deep or progressive cytopenia and/or splenomegaly. The use of interferon-α or splenectomy is preferable.

A Single-center Experience in Splenic Diffuse Red Pulp Lymphoma Diagnosis.

The World Health Organization 2008 classification highlighted a new nosology-splenic diffuse red pulp lymphoma (SDRPL) with clinical and laboratory features similar to both splenic marginal zone lymphoma and hairy cell leukemia (HCL) and variant form of HCL. Experience of hematologists on the diagnosis and differential diagnosis of SDRPL is extremely limited. The aim of our report was to characterize the clinical and immunomorphologic features of SDRPL on our own observations. During 2013-2014, in National Research Center for Hematology, 87 spleen specimens removed from various B-cell lymphomas were analyzed. In four (4.6%) cases, the diagnosis SDRPL was made based on morphologic, immunohistochemical, immunophenotypic, molecular examination of spleen biopsies, blood and bone marrow samples. In all cases of SDRPL were observed significant splenomegaly, lymphocytosis from 56% to 94% (in two cases with leukocytosis 55.000 and 75.000 109/l). The circulating "villous" lymphocytes phenotype was CD20+ (bright), CD11c+/±, CD103 (weakly)+/±, LAIR-1+, CD25-, CD5-, CD10-, and CD23-. Mutation BRAFV600E was not detected. Bone marrow with minor lymphoid CD20+, CD25-, Annexin1-, Cyclin D1- cell infiltration. The average weight of the spleen was 3900 g (1450-9500 g), and morphologically, there was revealed lymphoid infiltration of red pulp with phenotype CD20+, DBA.44+, CD25-, Annexin1-, Cyclin D1-, CD103-, CD123-, CD27-, focal SD11c± and TRAP±. Now patients are observed in remission: two patients after splenectomy, two after splenectomy and cladribine+rituximab chemotherapy. SRDPL-a rare lymphoma that is suspected in the cases with significant splenomegaly and lymphocytosis with villous lymphocytes forms that have only a part of the classic markers HCL, with minor bone marrow infiltration. The standard diagnosis and treatment is splenectomy. Differential diagnosis of SMZL and HCL has clear criteria, but criteria of differentiation with variant HCL are still unknown.

[Experience in investigating splenic red pulp lymphoma]. / Opyt izucheniya limfomy krasnoi pul'py selezenki.

AIM: To generalize hematologists' experience of the diagnosis and differential diagnosis of splenic red pulp lymphoma (SRPL). MATERIAL AND METHODS: Eighty-seven splenic biopsy specimens taken from patients with different B-cell lymphoproliferative diseases were examined in the Hematology Research Center in 2013-2014. The diagnosis of SRPL was based on the morphological, immunohistochemical, immunophenotypic, and molecular examinations of the splenic biopsy specimens, blood and bone marrow (BM) tests in 4 (4.6%) cases. RESULTS: There was significant splenomegaly in all SRPL cases, lymphocytosis in 56 to 94% (leukocytes, 55 and 75·109/l in 2 cases), circulation of hairy lymphocytes with the phenotypes CD20+ (markedly), CD11c+/±, CD103+/± (weakly), LAIR-1+, CD25-, CD5-, CD10-, and CD23-, which did not contain tartate-resistant acid phosphatase, without BRAFV600E mutation, BM with insignificant lymphoid infiltration of CD20+, CD25-, Annexin 1-, and Cyclin D1-. The weight of the spleen averaged 3900 g (1450-9500 g); its tissue exhibited lymphoid infiltration of the red pulp with the phenotypes CD20+, DBA.44+, CD25-, Annexin1-, Cyclin D1-, CD103-, CD123-, CD27-, focal СD11c±, and TRAP±. Four patients (2 after splenectomy (SE) and 2 after SE and chemotherapy with cladribine and rituximab) are being followed up in remission. CONCLUSION: SRPL is a rare disease that should be presumed to be in significant splenomegaly and lymphocytosis with hairy lymphocytes, which have only some markers for classical hairy cell leukemia (HCL), in minor BM lesion. SE is the standard for diagnosis and treatment. The differential diagnosis of SRPL with HCL has clear criteria and that with HCL-v is undetected.

[Efficiency of interferon therapy in patients with essential thrombocythemia or polycythemia vera]. / Effektivnost' interferonoterapii u bol'nykh essentsial'noi trombotsitemiei i istinnoi politsitemiei.

AIM: To evaluate the efficiency of interferon (IFN) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). SUBJECTS AND METHODS: A total of 61 patients (41 with ET and 20 with PV) were examined. Prior to study enrolment, 44 (72%) patients with ET or PV received one or other therapy (aspirin was not taken into account). The mean Jak2V617F mutant allele at baseline was 23% (6-54%) in the patients with ET and 40% (11-88%) in those with PV. The median time from diagnosis to enrollment was 49 months. RESULTS: The paper presents the clinical and molecular findings of long-term INF-α therapy in patients with ET or PV. The median follow-up was 52 months. Recombinant IFN-α2 showed its ability to induce complete hematologic remission (ET (76%), PV (70%)) and a complete molecular response. 22 (69%) out of 32 patients were noted to have a smaller number of cells with the Jak2V617F mutation. In the patients with PV and in those with ET, the relative reduction in the proportion of cells with the Jak2V617F mutant gene averaged 85% and 56% of the baseline values, respectively. There was a reduction in the proportion of cells expressing the Jak2V617F mutation in both the ET (from 12 to 2.2%; p=0.001) and PV (from 32.7% to 3.2%) groups (р=0.001). Ten (31%) patients achieved a deep molecular remission (≤2% Jak2V617F allele); among them, 5 patients were not found to have Jak2V617F mutation. The obtained molecular response remained in 7 of the 10 patients untreated for 11 to 86 months. The long-term treatment with IFN-α led to normalization of the morphological pattern of bone marrow in 5 of the 7 PV or ET patients. CONCLUSION: Significant molecular remissions achieved by therapy with recombinant interferon-α2 confirm the appropriateness of this treatment option in in the majority of patients with ET or PV.

[Isolated sacral injury in hairy cell leukemia: A case report and analysis of literature data].

Hairy cell leukemia (HCL), a chronic B-cell lymphoproliferative disease with special villous morphology and immunophenotypic markers of lymphoid cells, is characterized by the involvement of bone marrow and spleen. The paper describes a case of a 29-year-old female patient without abnormal clinical blood tests and myelograms, with normal spleen sizes, in whom the only manifestation of HCL was massive scrotal injury with a soft tissue component in the small pelvic cavity.

[Nodular lymphocyte-predominant Hodgkin's lymphoma: Principles of diagnosis and treatment].

AIM: To describe the clinical and morphological features of the rare Hodgkin's lymphoma (HL) subtype--nodular lymphocyte-predominant HL (NLPHL). SUBJECTS AND METHODS: Forty-two patients were diagnosed with NLPHL in 2010 to 2014. The male to female ratio was 2.2:1; the median age was 37 years (range 17-68 years). NLPHL was diagnosed on the basis of the histological and immunohistochemical examinations of tumor biopsy specimens; disease stages were determined by standard HL studies. RESULTS: Before NLPHL was detected, 23 (55%) patients were diagnosed as having HL in 13 cases, follicular lymphoma in 2, lymphofollicular hyperplasia in 3, angioimmunoblastic lymphoma in 1, diffuse large B-cell lymphoma in 3, and B-cell lymphoma (non-HL) in 1. Long-term (3-21-year; median 8 years) persistent lymphadenopathy was observed in 16 (38%) patients. Seventeen (40.5%) patients had early (I-II) stages of the disease and 25 (59.5%) had advanced stages. B symptoms were noted in 24% of cases. There was involvement of extranodal sites (salivary gland, tonsil) in 2 patients, spleen in 14 (33%), bone marrow in 8, and bulky disease in 2. Cycles of ABVD ± rituximab ± radiotherapy (RT) were used in early-stage NLPHL; those of R-BEACOPP-14 ± RT were performed in the advanced stages of the disease or its transformation to diffuse large B-cell lymphoma with excessive T cells. CONCLUSION: When patients have a history of long-term asymptomatic lymphadenopathy, it is necessary to rule out NLPHL, for which purpose an immunohistochemical examination of a biopsy specimen and its reexamination in a laboratory having experience in diagnosing NLPHL must necessarily be done. Lower RT doses and rituximab incorporated into the cycle of treatment are indicated to reduce its toxicity and to preserve therapeutic efficiency.

[Mass-spectrometric analysis of proteasomal subunits possessing endoribonuclease activity].

Proteasomes act as the main apparatus of non-lysosomal intracellular proteolysis and participate in the regulation of most important cellular processes. Despite considerable progress in the understanding of proteasome's functioning, some issues, in particular, RNase activity of these ribonucleoprotein complexes and its regulation remain scarcely explored. In this paper we found several proteins corresponding by electrophoretic mobility to subunits of the complex 20S proteasome to possess endoribonuclease activity with respect to both sense and antisense sequences of the c-myc mRNA 3'-UTR. Mass-spectrometric analysis of tryptic hydrolysates of these proteins revealed in the samples the presence of 20S proteasome subunits--αl (PSMA6), α5 (PSMA5), α6 (PSMA1) and α7 (PSMA3). A number of novel phosphorylation sites in subunits αl (PSMA6) and α7 (PSMA3), and the form of subunit α5 (PSMA5) with a deletion of N-terminal 20 amino acid residues detected. The observed differences of individual subunits in the possession endonuclease activity could be apparently explained by postranslational modifications of these proteins, in particular--by phosphorylation. It is shown that the specificity of the proteasomal RNase activity varies after dephosphorylation and also influenced by Ca and Mg cations. The conclusions made about the impact of the PTM status of proteasome subunits on the specificity of their RNase activity.

[Thrombosis of the sinus durae matris as a complication of therapy in patients with Hodgkin lymphoma].

AIM: To describe thrombosis of the sinus durae matris (TSDM) in lymphomas. SUBJECTS AND METHODS: 402 patients with Hodgkin lymphoma were treated using the BEACOPP-14 protocol in 2006 to 2013. Thrombotic events occurred in 6% of the patients, including 3 (0.8%) who developed brain magnetic resonance imaging-verified TSDM. RESULTS: TSDM developed in 3 women aged 17, 18, and 25 years during 3-6 chemotherapy cycles involving glucocorticosteroids in a dose of 80 mg/m2 on days 1-7 and an oral contraceptive used continuously for 1.5-3 months. The symptoms of thrombosis were severe headache; 2 patients had convulsive syndrome with short-term loss of consciousness. Anticoagulant therapy with intravenous heparin 20,000--24,000 U/day led to thrombus recanalization within 4-10 days. No rethromoboses were observed during a subsequent follow-up. CONCLUSION: The BEACOPP-14 treatment in young women with Hodgkin lymphoma who continuously take oral contraceptives should be combined with anticoagulant therapy, by monitoring their coagulogram.

[Viral mucosal lesions of the gastrointestinal tract organs in patients with lymphoma].

Infectious complications are one of the main causes of the lower efficiency of chemotherapy in hematologic oncology. The common infectious pathogens are herpes group viruses. The manifestations of herpesvirus infection or reactivation may be extremely diverse; just the same, digestive tract injury is rarely associated with herpesvirus infection in clinical practice. Viral mucosal injury of the intestine and pharynx is described in 2 patients with lymphomas during agranulocytosis. Virus-specific DNA was absent in blood; however, it was detected at high titers (the number of copies of 10(3) 10(5) genome-equivalent/mI) in feces and mucosal biopsy specimens. Addition of antiviral therapy could rapidly abolish infectious complications in both cases. Virological examination of material from the injury focus makes it possible to reveal a pathogenic virus even though the latter is undetectable in blood.

[Tuberculosis in patients with lymphoproliferative diseases].

AIM: To study the clinical manifestations, diagnosis, and treatment of lymphoproliferative diseases (LPD) concurrent with tuberculosis. SUBJECTS AND METHODS: In 1990 to 2013, the Hematology Research Center, Ministry of Health of Russia, followed up 4422 patients with LPD. Lymphomas and leukemias were diagnosed using the universally protocols. Tuberculosis was verified by the results of a comprehensive examination involving the histological study of biopsy specimens. RESULTS: Tuberculosis was identified in 85 (2%) patients with LPD. According to the nosological entity, the tuberculosis detection rates were 3% (40/1350) in Hodgkin lymphoma (HL), 1.2% (20/1627) in aggressive lymphomas, 1.4% (16/1136) in mature cell lymphomas and chronic lymphocytic leukemia, and 2.9% (9/309) in hairy cell leukemia. In accordance with its site, pulmonary tuberculosis was 73%; extrapulmonary tuberculosis, 14%; generalized tuberculosis, 12%. In pulmonary tuberculosis, its disseminated and focal involvements were found in 71 and 18% of cases, respectively. Tuberculosis was detected in 43% of the patients with HL in remission; it occurred only in other hemoblastoses in its active phase. When tuberculosis and LPD were simultaneously found, both diseases were concurrently treated. If the chemotherapy of LPD was effective, tuberculosis was cured in all the patients. CONCLUSION: Patients with LPD are a group at increased risk for tuberculosis. The diagnosis of recurrent LPD must be histologically proven. When tuberculosis and LPD are simultaneously found, both diseases should be concurrently treated.

[Pneumocystis pneumonia in patients with Hodgkin lymphoma].

AIM: To assess the results of diagnosing and treating Pneumocystis pneumonia (PP) in patients with Hodgkin lymphoma (HL) over 15 years. SUBJECTS AND METHODS: In 1999 to 2013, PP occurred in 22 (3%) of 741 HL patients receiving programmed polychemotherapy (PCT). The male/female ratio was 1:1.1; median age was 32 (18-65) years. Advanced stages (IIB-IV) of the disease were seen in 82% of the patients. The diagnosis of PP was established when Pneumocystis (more than 5 cysts in the specimen) was detected in the lavage fluid by indirect immunofluorescence assay. RESULTS: PP developed after 4 or more cycles of PCT. Along with Pneumocystis, all the cases were found to have additional pathogens: herpes virus in 72% and bacteria and fungi in 33%. All the patients received combined antimicrobial therapy using high doses of intravenous trimethoprim-sulfamethoxazole. Ten (45%) patients required mechanical ventilation (MV). The total mortality in PP was 32% (7 patients died); moreover, none of the patients without MV died whereas the mortality among those who had MV was 70% (7 of the 10 patients died). High death rates (80%) were noted among the patients with recurrent and resistant HL. CONCLUSION: PP should be prevented with trimethoprim-sulfamethoxazole in patients with LH during PCT. If respiratory failure and X-ray signs of interstitial pneumonia appear, there is a need for fibrobronchoscopy with bronchoalveolar lavage and comprehensive microbiological testing of lavage fluid.

[Differential diagnosis of thymic hyperplasia and mediastinal tumor in patients with lymphogranulomatosis after chemotherapy].

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 45patients. 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.

[A pharmacological cost-effective analysis of vobenzim use in combined treatment of chronic prostatitis].

A pharmacological cost-effective analysis of systemic enzymotherapy combination with fluoroquinolone antibiotics in the treatment of chronic bacterial prostatitis showed cost-effect of such therapy: medical cost efficacy of the treatment of chronic bacterial prostatitis with antibiotic + vobenzim is 2 times higher than of antibiotic treatment only.

[Proteasomes and their role in transcriptional regulation].

26S proteasome is a multisubunit protein complex that plays a pivotal role in protein degradation. Proteasome's enzymatic activities--proteolytic, ATPase/helicase and RNase--can be used in regulation of multiple cellular processes. Recent studies confirm the major role of proteasomes in transcriptional regulation. Although various post-translational modifications of proteasome subunits have been described, relatively little is known about their functional effect on regulation of proteasome-dependent gene expression. In this article, we talk about the role of proteasomes in control of gene expression and different stages of transcription.

[Recombinant proteasomal alpha-type subunits exhibit endoribonuclease activity].

26S proteasome is a multi-subunit protein complex that consists of the regulatory 19S and the catalytic 20S subcomplexes. The major cellular function of the proteasome is protein degradation. It has been found recently that the 20S particle, besides its proteolytic activity, also possesses endoribonuclease activity. The latter is mediated by two alpha-type subunits (alpha1 and alpha5). In this report we have analyzed the remaining alpha-type subunits for their ability to hydrolyze RNA. We found that all of the recombinant subunits tested exhibited endoribonuclease activity which depended on the origin of RNA and the presence of bivalent ions in the reaction. These results indicate that the endoribonuclease activity of proteasomes may play an important role in cellular metabolism of RNA.

[Treatment of life-threatening airway obstruction in patients with malignant lymphomas].

Case histories of patients with hemoblastosis admitted to a hospital for acute respiratory failure due to tumor-induced obstruction were retrospectively analyzed. The causes of obstruction, antitumor therapy, methods for provision of airway patency, and major critical syndromes were analyzed. Ten patients with life-threatening tumor-induced airway obstruction were hospitalized from 1995 to 2007. The patients suffered from malignant lymphomas in all cases. The causes of impaired airway patency were the compression of the trachea and large bronchi with a tumor, lymph nodes, affected thyroid, as well as the superior vena cava syndrome, and tumor-induced lesion of soft tissues of the neck and chest. Airway patency was effected with tracheal intubation in 9 cases, it was maintained by noninvasive mask ventilation in 1 patient. Translaryngeal tracheal intubation and tracheostomy were used for artificial ventilation (AV) in 6 and 3 patients, respectively. Multidrug therapy (MDT) was performed in all the patients. Airway patency restored in 9 patients after MDT initiation. The duration of AV was 5.8 +/- l.7 days. The length of stay in an intensive care unit was 90%; intrahospital survival was 70%; 28-day and 3-year survivals were 90 and 24%, respectively. Two of the 3 patients who had undergone were observed to have serious complications (cicatrical stenosis, tracheoesophageal fistula). Hemoblastosis patients with tumor-induced obstruction need for provision of airway patency and for immediate initiation of MDT and/or radiotherapy. Orothracheal or nasotracheal intubation of the trachea is the methods of choice in providing airway patency. Tracheostomy is not indicated in most cases. Short-term prognosis is good in this cohort of patients. Long-term prognosis is determined by a lot of factors of which tumor sensitivity to cytostatics and radiation is most important.

[Reprogramming of nuclear proteasomes in K562 cells undergoing apoptosis. I. Effect of glutathione-depleting agent, diethylmaleate].

Here we have studied changes in the subunit composition, phosphorylation state and enzymatic activities of 26S proteasomes in cells undergoing the programmed cell death. Apoptosis in proerythroleukemic K562 cells was induced by glutathione-depleting agent, diethylmaleate (DEM). We have shown for the first time that proteasomes isolated from the nuclei of control and induces K562 cells differ in their subunit patterns, as well as in the phosphorylation state of subunits on threonine and tyrosine residues. We observed trypsin- and chymotrypsin-like activities on nuclear proteasomes and the specificity of proteasomal nucleolysis of several individual messenger RNAs (c-fos and c-myc) to be changed under effect of DEM on K562 cells. Treatment of K562 cells with DEM leads to modification of zeta/alpha5 and iota/alpha6 proteasomal subunits associated with RNAse activity of proteasomes. These findings confirm our hypothesis about so-called reprogramming of nuclear proteasome population in undergoing apoptosis K562 cells which is manifested by the changes in proteasomal composition, phosphorylation state, and enzymatic activities during the programmed cell death.