[Follicular lymphoma. High-dose immunochemotherapy with autologous blood stem cell transplantation: Results of the first prospective study in Russia]. / Follikulyarnaya limfoma. Vysokodoznaya immunokhimioterapiya s transplantatsiei autologichnykh stvolovykh kletok krovi: rezul'taty pervogo prospektivnogo issledovaniya v Rossii.

AIM: to evaluate the efficiency of high-dose chemotherapy (HDCT) with further autologous blood stem cell transplantation (auto-BSCT) in the first-line therapy of patients with follicular lymphoma (FL) and poor prognostic factors. SUBJECTS AND METHODS: In 2000 to 2015, the National Research Center for Hematology, Ministry of Health of the Russian Federation, performed therapy in 39 patients with FL and poor prognostic factors (a total of 215 patients with FL). The R-CHOP treatment was done as induction therapy. Sequential HCT and further auto-BSCT were performed in 29 (74%) of the 39 patients, who had shown a partial tumor response to the induction therapy or achieved partial remission after 4-6 cycles of CT, but had poor prognostic factors. 22 of the 29 patients underwent auto-BSCT in first-line therapy after induction R-CHOP regimens. Among them, there were 17 men with a median age of 46 years (31-68 years). 21 of the 22 patients were recorded to have Stage IV by the Ann Arbor staging classification. Bulky peritoneal and retroperitoneal tumors larger than 7 cm were detectable at disease onset in 14 of the 22 cases. Two patients were noted to have phenomena of leukemization. 16 patients had bone marrow (BM) involvement. According to the Follicular Lymphoma International Prognostic Index-1 (FLIPI-1), the patients were divided into 3 groups: 1) a low risk (n=5); 2) an intermediate risk (n=3); a high risk (n=14). B-symptoms were observed in 16 cases. 16 patients were diagnosed with cytological grade I-II FL and 6 had grade IIIA. According to the tumor proliferative pattern, the distribution turned out to be as follows: nodular (n=6), nodular-diffuse (n=13), and diffuse (n=3). The proliferative activity index averaged 30% (8-90%). Serum and urine proteins were immmunochemically assayed in 18 cases, out of them 8 patients were diagnosed as having serum ß2-microglobulin concentrations above normal as a poor prognostic factor. In 14 of the 22 patients, the activity of lactate dehydrogenase was greater than normal (266-7806 U/l). RESULTS: Out of the 22 patients, 20 who have undergone auto-BSCT in first-line therapy are survivors and have remission of the underlying disease: 18 and 2 patients achieved complete and partial remission, respectively. The follow-up period was 7 to 178 months (median, 32 months). After auto-BSCT in the first remission, 2 patients developed disease recurrences: an early recurrence after 9 months in one case and a late recurrence 6 years after completion of therapy in the other. CONCLUSION: The first prospective study of intensive therapy for FL in Russia has demonstrated that HDCT with further auto-BSCT in first-line therapy allows complete remission in patients with poor prognostic factors and higher overall and progression-free survival rates.

[Late cardiotoxicity of high-dose chemotherapy according to the modified NHL-BFM-90 program in adult patients with diffuse large B-cell lymphoma].

AIM: To evaluate the late cardiotoxicity (CT) of high-dose chemotherapy (CT) according to the modified NHL-BFM-90 (mNHL-BFM-90) protocol in adult patients with diffuse large B-cell lymphoma (DLBCL). SUBJECTS AND METHODS: The results of electrocardiography (ECG) and echocardiography (echoCG) were analyzed in 40 DLBCL patients treated according to the mNHL-BFM-90 program in the Hematology Research Center (HRC), Russian Academy of Medical Sciences (RAMS), in 2002 to 2009. A study group consisted of 20 men and 20 women whose age was 31 to 76 years; median age was 56.5 years at the time of their examination and the median follow-up time after therapy was 6 years. The individual cumulative dose of doxorubicin was 150-300 mg/M2. A comparison group included 19 patients receiving CHOP/R-CHOP CT in HRC, RAMS, in 2002 to 2009. Out of them, there were 8 men and 11 women whose age was 39 to 78 years median age was 70 years at the time of their examination. The individual cumulative dose of doxorubicin was 200-400 mg/M2. ECG and echoCG were carried out before and 5 years or more after CT. RESULTS: Out of the 40 patients with DLBCL, the signs of subclinical cardiomyopathy (CMP) were detected in 24 (60%) patients; no clinical manifestations of congestive heart failure (CHF) were found in any patient. In the comparison group of 19 patients receiving CHOP/R-CHOP CT, 14 (74%) patients were found to have signs of subclinical CMP and no clinical signs of CHF. The summary toxicity index significantly depended on age (p=0.03) and a history of heart disease (p=0.3); it was significantly higher after CHOP/R-CHOP CT (p=0.05). There was a statistically significant relationship of the risk of subclinical CMP to the history of heart diseases (p=0.05). CONCLUSION: Late cardiotoxicity of the mNHL-BFM-90 program does not exceed the toxicity of standard CHOP/R-CHOP therapy. Post-CT Echo-CG and ECG findings showed that the patients with the most marked subclinical signs of CMP in both groups had cardiotoxicity risk factors, such as coronary heart disease, hypertensive disease, or diabetes in their history. No clinically significant CHF was identified in any patient.

[Diagnosis and treatment in patients with B-cell lymphoma unclassified that is intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma]. / Diagnostika i lechenie bol'nykh V-kletochnoi limfomoi neklassifitsiruemoi, zanimayushchei promezhutochnoe polozhenie mezhdu diffuznoi V-krupnokletochnoi limfomoi i limfomoi Berkitta.

AIM: To characterize a group of patients with B-cell lymphoma (BCLU) unclassified that is intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma, to identify poor prognostic factors, and to evaluate therapeutic efficiency in patients with BCLU. SUBJECTS AND METHODS: Twenty-five patients with BCLU were examined. Double-hit lymphoma (DHL) was diagnosed in 8 (32%) patients. According to the Ann-Arbor classification of lymphoma, its stages II, III, and IV were diagnosed in 3 (12%), 2 (8%), and 20 (80%) patients, respectively. MYC rearrangement was observed in 11 (48%) out of 23 patients: single-hit lymphoma in 3 patients and DHL in 8 (BCL2+/MYC+ in 6 cases and BCL6+/MYC+ in 2). The expression of с-MYC (cut off ≥40%) was revealed in 17 (74%) out of 23 patients; that of BCL2 (cut off ≥50%) was detected in 14 (58%) out of 24 patients; coexpression of both proteins was seen in 12 (52%) out of 23 patients. The DHL group showed a correlation between the rearrangement of the BCL2+/MYC+ genes and the expression of MYC and BCL2 proteins in 5 out of 6 patients. Taking into account the heterogeneity of the entire patient group, DHL and non-DHL subgroups were considered separately. Both subgroups were comparable by clinical characteristics. BCLU patients younger than 60 years of age received treatment according to the LB-M-04 ± rituximab; those aged 60 or older had CHOP-like regimens ± rituximab. Autologous stem cell transplantation (auto-SCT) was performed in 5 patients belonging to a high-risk group. RESULTS: The 3-year overall survival (OS) was 62% and the 3-year event-free survival (EFS) was 51%. The 3-year OS was lower for the DHL group than that for the non-DHL group (43 and 75%, respectively). CONCLUSION: In the DHL group, both OS and EFS are significantly lower (the risk of poor outcome, including death, is higher) than those in the non-DHL group. It is conceivable that intensified chemotherapy with auto-SCT increases treatment results in patients with BCLU; however, a larger number of observations are needed to obtain valid data.

[Experience with outpatient treatment for thromboses and thrombophilias].

AIM: To evaluate the efficiency of diagnosis and treatment of thromboses in patients with thrombophilia in an outpatient setting. SUBJECTS AND METHODS: One hundred and seventy-two patients with different forms of thrombophilic states were examined. One hundred and thirty-two patients were found to have genetic mutations, of them 125 patients had multiple mutations. Thromboses were diagnosed in 130 patients with genetic disorders. RESULTS: The most common laboratory markers of thrombophilias were hyperhomocysteinemia (55%), sticky platelet syndrome (41%), and laboratory findings of antiphospholipid syndrome. Thrombogenic mutations, such as plasminogen activator plasminogen inhibitor-1 (73%), methylene tetrahydrofolate reductase (60%), platelet glycoprotein 1a receptors (50%), and fibrinogen (42%), were most often diagnosed. The efficiency of treatment was shown to largely depend on the duration of an initial thrombotic process. CONCLUSION: Outpatient treatment for thromboses is more economical and comfortable for patients. To avoid hospital admissions, it is necessary to time detect the disease and to start its treatment as soon as possible. The concurrent use of ultrasonography, genetic and laboratory diagnostic methods accelerates the identification and localization of the pathology, which facilitates its treatment and frequently rules out the need for patient hospitalization.

[A case of spontaneous chylothorax complicating pregnancy].

The paper gives a clinical case of left-sided chylothorax developing in a young woman in the second half of pregnancy due to thrombosis of the left internal jugular vein, left subclavian vein, and brachiocephalic trunk. Cesarean section was made. Medical treatment thereafter proved to be effective. The possible mechanisms for spontaneous venous thrombosis and chylothorax during pregnancy and the methods of their diagnosis and treatment are discussed.

[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.

[Peculiarities of course of extramural pneumonia among military servicemen in conditions of local war and armed conflicts].

The aim of work was examination of peculiarities of outhospital pneumonia (OHP) among military servicemen, participants of local armed conflicts in areas of Prodnestrovie, Tadjikistan, North Ossetia, Abkhazia. There were retrospectively analyzed 139 archive patient histories of military servicemen, got pneumonia during 1990-1993. In structure of OHP of military servicemen predominating was pneumonia with not hard course of disease. Was educes a clear season dependence of appearance of pneumonia in described conditions with it's peculiarities. Each fifth patient form call-up contingent had deficit of weight. It influenced on course of disease. In 40% of cases of OHP there were coexistent diseases. Peculiarities in clinical forms of disease were not found. Using of antibacterial measures in treatment of OHP was empirical, during therapy of acute pneumonia were used 3 antibiotics simultaneously. For a more long-term of treatment had a need soldiers, participants of combat actions on the Northern Caucasus.

[Peculiarities of the immune status of soldiers taken ill with extramural pneumonia during battle action].

The article deals with violations of general resistance of the organism of military men, who get extramural pneumonia during the battle action. The author analyzed the data of immune status in three groups of soldiers. Statistical analysis of materials led to the conclusion that violations of immunity in the main group depend on the circumstances and nature of military service. This fact indicates that the significant clinical and pathogenetic differences in the development, course and outcome of an extramural pneumonia against the background of chronic adaptation syndrome. Pathogenic peculiarities of patients with pneumonia against the background of the impact of extreme factors of the military conflicts are presented in a prolonged dysfunction of all parts of the immune system.

[Efficacy of conservative treatment of gastric lymphosarcoma].

AIM: To compare efficacy and toxicity of conservative therapy (different programs of polychemotherapy) of gastric lymphosarcoma conducted for the last 10 years in Hematological Research Center of the Russian Academy of Medical Sciences. MATERIAL AND METHODS: The study included 63 patients (40 females and 23 males aged 14 to 78 years, mean age 49 years) with primary diagnosis of gastric lymphosarcoma (GL). Of them, 56 (89%) patients had diffuse large B-cell lymphosarcoma (DLBCL) and 7 (11%) had gastric Berkitt's lymphoma (BL). Only detection of t(8;14) with rearrangement of c-myc gene provided accurate diagnosis of gastric BL. By the treatment DLBCL patients were divided into two groups: 44 patients of group 1 received polychemotherapy (PCT) according to CHOP scheme or in combination with radiotherapy and surgical treatment; 12 patients of group 2 were treated according to modified program mNHL-BFM-90, without surgical or radiation treatment. Of 7 patients with gastric BL 5 patients received treatment according to a modified program mNHL-BFM-90 and 2 patients were given CHOP because of DLBCL misdiagnosis without cytogenetic detection of t(8;14). RESULTS: Overall survival in group 1 was 73% in mean follow-up 61 months. The survival depended only on initial factors of poor prognosis (PPF): tumor size over 10 cm, Ann-Arbor stage higher than IE, B-symptoms, elevated level of LDH. Overall survival of 18 gastric DLBCL patients without PPF reached 94%, of 26 patients with PPF - 60%. Lethality due to side effects was 4% (2 patients), primary resistance was 14% (6 patients), recurrence arose in 9% (4 patients). Overall survival in group 2 was 100% in mean remission duration 18 months, was unrelated to PPF (10 of 12 patients) but correlated with high toxicity. 5 BL patients treated with a modified mNHL-BFM-90 program achieved remission (a mean follow-up at present is 1 to 50 months, mean 24 months). 2 BL patients treated with CHOP died for a year. CONCLUSION: Gastric lymphosarcomas are sensitive to chemotherapy, thereby PCT only is effective in most patients. PPF in gastric DLBCL were responsible for poor outcome in 40% patients in CHOP treatment. The modified program mNHL-BFM-90 can produce up to 100% complete long-term remissions in therapy of gastric lymphosarcoma in adults both in BL and DLBCL patients. A cytogenetic examination of c-myc gene rearrangement is obligatory before initiation of PCT of gastric lymphosarcoma.

[Gamma-scintigraphy with Ga-67 citrate in differential diagnosis of residual tumors in lymphogranulomatosis and lymphosarcoma].

AIM: To study informative and diagnostic efficacy of quantitative evaluation of the results of gamma-scintigraphy in patients with lymphogranulomatosis and lymphosarcoma with prevalent mediastinal and pulmonary lesions. MATERIAL AND METHODS: 100 patients with verified lymphogranulematosis were studied: 67 with lymphosarcoma and 33 with mediastinal involvement. The mediastinal tumor monitoring was made before therapy, in complete clinicohematological remission, in progression using a complex of radio-, clinicohematological, histomorphological and radionuclide methods. RESULTS: A comparative analysis of the findings of radiation, radionuclide and histomorphological examinations of the removed residual mediastinal tumor in 10 patients showed that scintigraphic evidence was similar to that of histological findings in most of the examinees. CONCLUSION: A high diagnostic efficacy of a complex of radiation and radionuclide methods with Ga-67 citrate based on estimation of accumulation intensity providing comprehensive information about mediastinal tumor is demonstrated. A comparative analysis was made of the results of radiation, radionuclide and histomorphological examinations of the removed residual lesion of the mediastinum in 10 patients. In most cases, scintigraphic findings coincided with the results of histological studies of biopsies of mediastinal residual lesion.