Follicular lymphoma (FL) is a tumor that develops from the B cells of the germinal center; characterized by recurrent and remitting course of the disease, the transformation of a tumor into diffuse large B-cell lymphoma (DLBCL) is possible. In generalized lesions and progression of FL, the most commonly used courses are R-CHOP and R-B. The choice of therapy for different cytological types, clinical and laboratory parameters remains disputable. Aim. To analyze the clinical, laboratory, morphological parameters of patients with FL, who got R-B and R-CHOP therapy; determine the criteria for selecting induction therapy. Materials and methods. The study included 203 patients with FL from 2000 to 2018. R-CHOP treatment was initiated in 126 patients, 14 of whom later received high-dose therapy (HDT) (R-DHAP: rituximab, dexamethasone, cisplatin, cytarabine) without autologous stem cell transplantation (autoSCT), 21 - HDT with autoSCT; treatment of 89 patients was limited to courses of R-CHOP and maintenance therapy with rituximab, two patients (in whom the disease progressed, despite R- CHOP therapy) were assigned the mNHL-BFM-90 program. The efficacy of treatment on various treatment regimens was evaluated primarily by overall survival. Results and discussion. R-B. 77 patients received R- B therapy. Complete remission of the disease was achieved in 47/77 (61%) patients (3 of them later developed a relapse of the disease), partial remission was achieved in 15/77(19%) patients, in 13/77 (17%) cases progression was recorded tumors. 70 patients had 1-2 cytological type of tumor, 6 patients - 3A cytological type. In cases of progression, 3 of 13 patients (46%) were diagnosed with 3A cytological type FL. Median observation (at the time of analysis) - 34 months. R- CHOP. 89 patients with FL received high- dose therapy with R- CHOP (6-8 courses) and maintenance therapy with rituximab. In 39 (44%) patients, the disease remained in remission, and in 50 (56%), a relapse of the disease developed. 50 patients had 1-2 cytological types, 39 - 3 cytological types. In cases of recurrence of FL, a 3A cytologic type (36%) was diagnosed in 18/50 patients. Median observation - 93 months. R- CHOP + HDT and autoSCT. 21 patients after the R- CHOP courses continued (due to insufficient antitumor response) high- dose chemotherapy (HDT) and autoSCT were performed. In 18/21 (86%) cases, complete remission of the disease was achieved and maintained, in 3 (14%) cases relapse developed. 16 patients had 1- 2 cytological types, 5 - 3 cytological types. Median observation - 81 months. R-CHOP + HDT without autoSCT. 14 patients started therapy under the R- CHOP program as induction therapy, but then (due to insufficient antitumor response), the treatment was continued according to the HDT without autoSCT. 11 (79%) patients are currently in remission of the disease, in 3 (21%) there was a relapse. 10 patients had 2 cytological types of PL, 4 - 3 cytological types. 11 (79%) patients are currently in remission of the disease, in 3 (21%) - there was a relapse. Median observation - 80 months. 7-year OS of patients with FL on RB therapy was 89% (95% CI 75- 99), on R- CHOP therapy - 85% (95% CI 73- 90), on R- CHOP + HDT and autoSCT - 87% (95% CI 57-100), on R- CHOP + HDT without autoSCT - 82%. 7-year PFS of FL patients on RB therapy was 70% (95% CI 75- 99), on R- CHOP therapy - 44% (95% CI 73- 90), on R- CHOP + HDT and autoSCT - 74% (95% CI 57- 100), on R- CHOP + HDT without autoSCT - 80%. Conclusion. The R- B is most effective in FL 1 and 2 cytological types. The cytological type does not correspond to the type of tumor growth: at 3A and 3A + 3B cytological types, nodular/nodular-diffuse and diffuse types of growth are found. When choosing an induction course, one should look at the cytological type of FL. A high proliferative activity index (according to Ki67) is a predictor of resistance to R- B therapy. The absence of an interfollicular T-cell reaction in tumor tissue FL is associated with tumor chemoresistance. The presence of the bulky factor is associated (in most patients) with the FLIPI index with values from 3 to 5, and is a predictor of a poor response to therapy. Patients with bulky, high (more than 35%) Ki67 index and FLIPI from 3 to 5 in the debut of the disease as the first line therapy, it is preferable to choose the R-CHOP mode, and in the absence of (after 4-6 courses) to complete or partial remission to continue conducting the HDT.

AIMTo characterize a group of patients with follicular lymphoma (FL) with leukemization and to evaluate the efficiency of different therapy options (R-CHOP/R-FMC/high-dose chemotherapy (HDCT)).SUBJECTS AND METHODS18 (7.2%) out of 250 patients diagnosed with FL, who were examined and treated at the National Research Center for Hematology, Ministry of Health of the Russian Federation, were found to have leukemic FL (tumor cells in the peripheral blood smears were detected by cytology and flow cytofluorometry. Eight of the 18 patients had extranodal foci of involvement: lung, stomach, spleen, lumbar muscles, upper jaw, and vertebrae. Bone marrow was involved in 17 of the 18 patients. Tumor biopsy specimens displayed a morphological pattern of indolent FL in the majority of patients (10 of the 18 patients had cytological grade 1-2 tumors and 14 patients had a nodular or nodular-diffuse tumor growth pattern). The patients underwent R-CHOP/R-FMC) or HDCT cycles as first-line therapy, followed by autologous stem cell transplantation (auto-SCT).RESULTSThe median follow-up was 66 months (range 12-217 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 70% (10% SEM) and 35% (15% SEM), respectively. The median OS was not reached; the median PFS was 3 years.CONCLUSIONLeukemic FL is characterized by low OS and PFS rates. The most effective chemotherapy regimens were R-CHOP, followed by HDCT and auto-SCT in first remission or R-FMC. These cycles can to a greater extent achieve a complete eradication of the bone marrow tumor clone. Due to the relapsing course of FL and the aggressiveness of leukemic FL, it is expedient to carry out auto-SCT in first remission.

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 β2-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.

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.

B-cell lymphoma that is unclassifiable and intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt's lymphoma (BL) - (UBL) is an aggressive lymphoma that has simultaneously morphological, immunophenotypical, and cytogenetic signs of both DLBCL and LB. At the same time due to its biological characteristics and clinical manifestations, UBL cannot be referred to as one of the above nosological entities. UBL has been first identified as an individual nosological entity in the 2008 World Health Organization classification. The review details the epidemiology, clinical manifestations, morphological pattern, immunophenotypic and karyotypic features, as well as therapeutic approaches and prognostic factors.

AIM To evaluate the efficiency and toxicity of the intensive Burkitt's lymphoma (BL) therapy protocol BL-M-04. SUBJECTS AND METHODS A total of 70 patients diagnosed with BL, including 45 men and 25 women whose age was 15 to 62 years (median age 31 years), were followed up in 2003 to 2014. Stage I (according to S. Murphy) was diagnosed in 4 (5.7%) patients; II in 9 (12.9%), III in 25 (35.7%), IV in 11 (15.7%), and Burkitt's leukemia in 21 (30%). There were tumor involvements of the bone marrow and central nervous system in 23 (32.9%) and 15 (21.4%) patients, respectively. B symptoms were detected in 56 (80%) patients; enhanced lactate dehydrogenase (LDH) activity was found in 50 (78.1%) out of 64 patients; moreover, in 34 (56.2%) out of 64 patients, LDH activity was more than twice as high as the reference values. The median LDH activity was 2398 (238-20,300) U/I. Acute renal failure at disease onset was identified in 17 (24.2%) patients; chemotherapy was initiated in 8 patients during renal replacement therapy. The treatment was performed using the BL-M-04±R protocol (4 successive blocks of A-C-A-C±R). Six blocks of A-C-A-C-A-C with rituximab has been carried out in patients with bone marrow involvement since 2011. RESULTS Sixty-two (89%) patients achieved complete remission. At this time, 6 patients died from therapy complications during remission induction; 2 patients were observed to have disease progression; 3 developed disease recurrence (2 patients had early recurrence; 1 patient developed recurrence 2 years after treatment). Five-year overall survival (OS) was 85%; 5-year relapse-free survival (RFS) was 95%. The Cox multivariate regression analysis revealed that Burkitt's leukemia and bone marrow involvement were independent factors that influenced OS and RFS. The poor somatic status (3-4 ECOC scores versus 0-2 scores) proved to be statistically significant for OS rather than RFS. CONCLUSION Despite the optimistic results obtained by our study group, there is a need to further improve BL treatment protocols and to elaborate novel approaches to therapy particularly for older patients and patients with Burkitt's leukemia.

AIMTo make a differential diagnosis of diffuse large B-cell lymphoma (DLBCL) with primary involvement of the mediastinal lymph nodes (LN) and primary mediastinal large B-cell lymphoma (PMLBCL); to evaluate the efficiency of a modified NHL-BFM-90 (M-NHL-BFM-90) program in the treatment of the above nosological entities.SUBJECTS AND METHODSThe investigation enrolled 60 patients with large B-cell lymphoma (LBCL) with primary involvement of mediastinal LN who had been treated at the Hematology Research Center, Ministry of Health of Russia, in 2004 to 2012. The diagnosis of PMLBCL and DLBCL with primary involvement of mediastinal LN was based on histological findings, the phenotype of tumor cells, and molecular evidence. Treatment was performed according to the M-NHL-BFM-90 program. Three pregnant women received predelivery polychemotherapy (PCT) according to the VACOP-B protocol and continued to have a DexaBEAM chemotherapy regimen 3-4 weeks postpartum. In case of a residual mass, all the patients underwent consolidation radiotherapy to the mediastinal area in a total focal dose of 36 Gy.RESULTSThe diagnosis of PMLBCL was established in 39 patients: 10 men and 29 women whose ages were 18 to 60 years (median age 30 years); DLBCL with primary involvement of mediastinal LN was verified in 21 patients: 8 men and 13 women whose age was 21 to 70 years (median age 30 years). After m-NHL-BFM-90 treatment protocol, 5-year overall survival rates in the patients with DLBCL with primary involvement of mediastinal LN and in those with PMLBCL were 95+/-5 and 86+/-6% and 5-year event-free survival rates were 95+/-5 and 78+/-7%, respectively. All the pregnant women diagnosed with PMLBCL who had received the VACOP-B --> delivery--> Dexa-BEAM PCT regimen during pregnancy achieved remission. The follow-up periods were 30, 36, and 42 weeks.CONCLUSIONThe patients with new-onset LBCL and primary involvement of mediastinal LN are a heterogeneous group that includes patients having two different diagnoses: PMLBCL and DLBCL. The efficiency of high-dose PCT is different in the patients with DLBCL with primary involvement of mediastinal LN and in those with PMLBCL (in spite of their similar clinical features, similar epidemiological characteristics, and the presence of the same unfavorable prognostic factors at onset).

AIM:To analyze the causes of renal lesion in patients with Burkitt's lymphoma (BL) and to develop optimal treatment policy.MATERIALS AND METHODS:The data of examination and treatment were analyzed in 20 patients with BL (14 men and 6 women aged 15 to 57 years (median age 24 years)) who had been followed up for renal lesion at the Hematology Research Center (HRC) in 2003 to 2011. When admitted to hospital, all the patients were found to have ureteric compression, renal parenchymal tumor infiltration, massive tumor cytolysis syndrome (MTCS). Polychemotherapy (PCT) was performed in accordance with the original intensive BL-M-04 protocol. The extent of the process was estimated according to the classification developed by S.B.Murphy: L3 variant B of acute lymphoblastic leukemia in 10 cases; Stage IV in 2; Stage III in 8. Acute renal failure (ARF) was identified in 13 patients. A control group comprised 36 patients with BL without ARF who had been followed up at the HRC in 2003 to 2011 and included into the BL-M-04 protocol. The ratio of patients with bone marrow lesion was 7:13 and 9:36 in the BL + ARF and BL-ARF groups, respectively.RESULTS:Decreased urine specific gravity and proteinuria (0.4 to 1.3 g/l) were the first manifestations of renal lesion and were seen in approximately 50% of all cases both on admission to hospital and in the first stages of PCT (10 and 9, 8 and 7 of the 20 cases, respectively). Microhematuria more commonly developed after initiation of PCT (7 and 3 of the 20 cases, respectively). ARF was diagnosed in 13 patients (24% of the 55 BL patients followed up at HRC in 2003 to 2011). One female patient developed ARF after the start of PCT. Twelve patients developed this condition at the onset of disease; in 4 patients, ARF existing prior to PCT began progressing after drug administration. The etiology of ARF was generally mixed. At the onset of disease, MTCS (n = 6) and specific renal parenchymal infiltration (n=6) were more common causes of ARF. Postrenal anuria was present in 2 cases. ARF after PCT initiation resulted from the toxic effects of methotrexate and MTCS (3 and 4 cases, respectively). ARF regressed in the early periods: in the prophase (n = 4) and during or the first PCT block A (n = 9). The BL patients with ARF, as compared to those without the latter, showed a statistically significant earlier onset of myelotoxic agranulocytosis (MTA): on day 3 of an intercourse interval (95 CI from 0 to 3 days) versus its day 5 (95% CI from 2 to 5 days) and a statistically significant longer duration of MTA--12 days (95% CI from 7 to 16 days) versus 7 days (95% Cl from 3 to 10 days); they were observed to have more severe mucositis. Despite the longer intercourse interval, 10 patients with ARF achieved remission; 4 patients died from therapy-refractory sepsis and 1 patient from thrombocytopenia. In the patients with ARF, mortality rates were significantly higher than in those without ARF (33% versus 10%; p = 0.04).CONCLUSION:Although there is a high risk of worsening renal dysfunction, PCT is a necessary condition for ARF resolution in BL.

AIM:To evaluate the efficiency of intensive polychemotherapy (PCT) in adult patients having diffuse large B-cell lymphoma (DLBL) of bones and soft tissues with and without poor prognostic factors (PPF).SUBJECTS AND METHODS:Out of 58 enrolled patients, 51 were diagnosed as having DLBL. Burkitt's lymphoma (BL) was diagnosed in 6 patients. One patient had marginal zone B-cell lymphoma. Thirty-five patients with DLBL (10 patients with PPF and 25 without PPF) and 3 patients with BL were treated with the CHOP/R-CHOP regimen. The NHL-BFM-90 program was used in 3 patients with BL and 16 with DLBL (15 patients with PPF and 1 patient without PPF).RESULTS:After radiotherapy, the patient with marginal zone B-cell lymphoma achieved a 20-month remission; three BL patients receiving CHOP died. All the BL patients receiving NHL-BFM-90 achieved complete remissions of 48 to 72 months. In 9 patients having DLBL without PPF, who received CHOP, five-year overall and event-free survival rates were 100%; in 22 patients with PPF, these were 50 and 45%, respectively. In the patients with and without PPF, who received CHOP/R-CHOP, the survival rates differed statistically significantly (p = 0.01; logrank test). In the group of 15 patients having DLBL with PPF, who were treated with the NHL-BFM-90 protocol, 14 achieved an average remission of 17 months. In the patients having DLBL with PPF who used NHF-BFM-90, therapeutic efficiency was significantly higher (p = 0.05; Fisher's exact test).CONCLUSION:Differential therapy for primary lymphomas of bones and soft tissues indicated that the NHL-BFM-90 protocol used in the PPF group was significantly more effective than the CHOP regimens.

Воробьев И.А., кандидат биологических наук, заместитель руководителя проблемной научно- исследовательской лаборатории клинической и профилактической гастроэнтерологии, Государственное бюджетное научное учреждение Тюменской области «Тюменский отдел Южно-Уральского научного центра РАМН» (Тюмень); тел.: 8-3452-759968; e-mail: trmo@mail.ru Vorobyev I.A., candidate of biological sciences, deputy supervisor of problematical scientific research laboratory of clinical and prophylactic gastroenterology, the state budgetary scientific establishment of Tyumen region «Tyumen branch of South Ural Research center of Russian Academy of Medical sciences» (ТВ SURC RAMS) (Tyumen); ph.: 8-3452- 759968; e-mail: trmo@mail.ru. Репина В.В., врач-аллерголог, младший научный сотрудник проблемной научно-исследовательской лаборатории клинической и профилактической гастроэнтерологии, Государственное бюджетное научное учреждение Тюменской области «Тюменский отдел Южно-Уральского научного центра РАМН» (Тюмень); тел.: 8-3452-209900; e-mail: gkdc@bk.ru Repina V.V., allergy doctor, junior scientific member of problematical scientific research laboratory of clinical and prophylactic gastroenterology, the state budgetary scientific establishment of Tyumen region «Tyumen branch of South Ural Research center of Russian Academy of Medical sciences» (ТВ SURC RAMS) (Tyumen); ph.: 8-3452-209900; e-mail: gkdc@bk.ru. Ростовщикова К.А., врач-гастроэнтеролог, младший научный сотрудник проблемной научно- исследовательской лаборатории клинической и профилактической гастроэнтерологии, Государственное бюджетное научное учреждение Тюменской области «Тюменский отдел Южно-Уральского научного центра РАМН» (Тюмень); тел.: 8-3452-209900; e-mail: gkdc@bk.ru Rostovcshikova K.A., gastroenterology doctor, junior scientific member of problematical scientific research laboratory of clinical and prophylactic gastroenterology, the state budgetary scientific establishment of Tyumen region «Tyumen branch of South Ural Research center of Russian Academy of Medical sciences» (ТВ SURC RAMS) (Tyumen); ph.: 8-3452- 209900; e-mail: gkdc@bk.ru. Шарапова Л.П., заместитель главного врача по медицинской части государственного лечебно- профилактического учреждения Тюменской области «Консультативно-диагностический центр»; Государственное лечебно-профилактическое учреждение Тюменской области «Консультативно- диагностический центр» (Тюмень); тел.: 8-3452- 209900; e-mail: gkdc@bk.ru Sharapova L.P., deputy head doctor of medical department of the state treatment-and-prophylactic establishment of Tyumen region «Advisory-diagnostic centre»; the state treatment-and-prophylactic establishment of Tyumen region «Advisory-diagnostic centre» (Tyumen); ph.: 8-3452-209900; e-mail: gkdc@bk.ru

Соколов С.А., кандидат медицинских наук, старший научный сотрудник проблемной научно- исследовательской лаборатории клинической и профилактической гастроэнтерологии, Государственное бюджетное научное учреждение Тюменской области «Тюменский отдел Южно-Уральского научного центра РАМН» (Тюмень); тел.: 8-3452-759968; e-mail: gkdc@bk.ru Sokolov S.A., the candidate of medical sciences, senior scientific member of problematical scientific research laboratory of clinical and prophylactic gastroenterology, the state budgetary scientific establishment of Tyumen region «Tyumen branch of South Ural Research center of Russian Academy of Medical sciences» (ТВ SURC RAMS) (Tyumen); ph.: 8-3452- 759968; e-mail: gkdc@bk.ru. Чеснокова Л.В., кандидат медицинских наук, заведующий амбулаторно-поликлиническим отделением, многопрофильная клиника Тюменской государственной медицинской академии (Тюмень); тел.: 8-345-2202197; e-mail: tyumsma@tyumsma.info Chesnokova L.V., the candidate of medical sciences, head of out polyclinic department of polyprofile clinic Tyumen State Medical (Tyumen); ph.: 8-345-2202197; e-mail: tyumsma@tyumsma.info. Воробьев И.А., кандидат биологических наук, заместитель руководителя проблемной научно- исследовательской лаборатории клинической и профилактической гастроэнтерологии, Государственное бюджетное научное учреждение Тюменской области «Тюменский отдел Южно-Уральского научного центра РАМН» (Тюмень); тел.: 8-3452-759968; e-mail: trmo@mail.ru Vorobyev I.A., candidate of biological sciences, deputy supervisor of problematical scientific research laboratory of clinical and prophylactic gastroenterology, the state budgetary scientific establishment of Tyumen region «Tyumen branch of South Ural Research center of Russian Academy of Medical sciences» (ТВ SURC RAMS) (Tyumen); ph.: 8-3452- 759968; e-mail: trmo@mail.ru

Aim. To diagnose diffuse large B-cell lymphosarcoma (DLBCLS) with primary involvement of the mediastinal lymph nodes (LN) and to evaluate the efficiency of aggressive polychemotherapy (PCT).Subjects and methods. The study included 15 patients (6 men and 9 women aged 18 to 70 years; median 38 years) followed up at the Hematology Research Center, Russian Academy of Medical Sciences, in 2004 to 2009. Three and 12 patients had Stages II and IIE DLBCLS, respectively. B symptoms were found in 14 (93.4%) patients. Increased lactate dehydrogenase (LDH) concentrations were detectable in 14 (93.4%) patients; tumors of 10 cm or more (bulky disease) were seen in 11 (73.3%). Enlarged cervical, supraclavicular, and axillary lymph nodes were found in 9 (60%) patients; lung involvement via extension in 9 (60%), and invasion into the pericardium in 5 (33.3%) and soft tissues of the anterior thoracic wall in (13.3%). There were no signs of involvement of extranodal organs at the moment of diagnosis. All the 15 patients received PCT according to the modified NHL-BFM-90 program: 4 to 6 courses depending on the response to the therapy; 10 (66.6%) and 5 (33.3%) patients had 4 and 6 courses, respectively; for consolidating purpose, 11(78.5%) patients were prescribed radiotherapy applied to the mediastinum in a cumulative dose of 36 Gy due to the fact that they had a residual mass.Results. Thirteen (86.6%) patients achieved a complete remission (CR). Primary PCT resistance was confirmed in one case. Another patient was stated to have near-complete remission. No recurrences were notified during the follow-up. The mean CR duration was 24.5 (range 2-49) months.Conclusion. DLBCLS with primary LN involvement is an individual nosological entity to be differentiated from primary mediastinal large B-cell lymphosarcoma. In most cases, DLBCLS shows signs of a poor prognosis, which makes it necessary to perform aggressive PCT.

Aim. To study the efficiency of polychemotherapy (PCT) for hemoblastoses in acute respiratory failure (ARF). Subjects and methods. The case histories of 63 hemoblastosis patients with ARF who received PCT were examined. The patients were divided into 3 groups: 1) 40 patients with acute leukemia (AL); 2) 15 patients with lymphomas; 3) 8 with multiple myeloma (MM). Results. The duration of lung lesion in leukemia was less than that in myeloma and lymphomas (2.5 +/- 5.3 versus 12.8 +/- 30.6 and 21 +/- 10.2 days, respectively). In the patients with leukemia and lymphomas, PCT was initiated earlier than in those with myeloma (1.5 +/- 0.5 versus 1 75 +/- 3.1 and 8.3 +/- 10.9 days, respectively). In 65.1% of the patients, PCT resulted in agranulocytosis, the rate and duration of which did not differ in the groups. APACHE II scores were 23.5 +/- 4.2, PaO2/FiO(2), was 182.1 +/- 60.5. The groups did not differ in disease severity. Noninvasive ventilation was made in 22 patients. Artificial ventilation (A V) was used in 39 patients; it was successfully completed in 13 (33 31%) patients. The most common infectious complications were sepsis (60916), septic shock (27916), and bacteremia (16%). Sepsis was encountered twice more frequently in lymphomas and myeloma, and septic shock was 4 times more commonly in leukemias. In myeloma, bacteremia was seen more frequently than in leukemia (50 and 10116; p = 0.024); serum procalcitonin was > 10 ng/ml (100 and 3596); p = 0.028). In leukemias, lymphomas, and myeloma, 28-day survival was 60, 60, and 7596, respectively. The baseline APACHE H disease severity, the degree of hypoxemia, and the presence and duration of agranulocytosis did not determine prognosis. The poor predictors were consciousness impairment, AV, renal failure, and no response to chemotherapy.

Aim. To make a comparative morphometric analysis of the nuclei and nucleoli of tumor cells in lymphogranulomatosis (LGM), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (A L CL) for differential diagnosis of these lymphomas.Material and methods. Biopsy material (lymph node biopsies) was frozen in hexan, fixed and stained, then microscopic pictures were made.Results. Mean area a tumor cell nuclei in LGM was 97.25 +/- 68.77 mcm(2), in DLBCL and ALCL - 55.89 +/- 20.13 mcm(2) and 70.31 +/- 34.64 mcm(2) respectively. The area differences were significant (p < 0.001). Hodgkin's and Berezovsky-Rid-Sternberg cell bucleoli area was the largest (11.44 +/- 7.83 mcm(2)). The nucleoli of the former are larger than those of the latter. Mean area of the nucleoli in DLBCL was 3.05 +/- 1.58, in ALCL - 5.53 +/- 4.94 mcm(2). The differences are significant (p < 0.001).Conclusion. Nucleoli in Hodgkin's cells are significantly larger than those in the tumor cells in ALCL and DLBCL and the nucleoli with the area more than 12 mcm(2) can be used in differential diagnosis between LGM and DLBCL but not between LGM and ALCL.

Primary CNS lymphomas have worse prognosis than other extranodal lymphomas: remissions are rare, recurrences are frequent. Literature is analysed on diagnosis, prognostic factors, perspectives and problems of treatment of primary CNS lymphomas.

AIMTo define complex of parameters characterizing transformation of skin T-cell tumors in lymphosarcoma; to show specific treatment of patients with this transformation.MATERIAL AND METHODSOf 57 patients with primary T-cell lymphomas of the skin (mycosis fungoides, Sezary's disease), we studied 12 patients with transformation of the process into lymphosarcoma by clinical, histological, moleculobiological and immunophenotypical parameters.RESULTSWe found that transformation of T-cell lymphoma into lymphosarcoma occurred in different time from the disease onset (2-12 years). In patients with mycosis fungoides (MF) the transformation was local while in those with Sezary's disease (SD) transformation of the tumor clone was determined by appearance of peripheral blood tumor cells rejuvenation. Morphological alterations were accompanied with immunomorphological parameters of progression. Most significant of them were high expression of the proliferative activity marker Ki-67 (10-70%), enhancement of activation (CD30, CD25), loss of some linear T-cell markers. Treatment of lymphosarcoma arising on the background of lingering MF or SD may combine two types of antitumor treatment--intensive and supporting because of coexistence of different clones of one tumor.CONCLUSIONVerification of skin T-cell lymphoma diagnosis and its transformation into lymphosarcoma must be based on the evidence from a number of examinations: histological, immunophenotyping, moleculobiological and clinical. Among criteria of the transformation, markers of lymphoproliferative activation are of great importance.

Primary skin large B-cell lymphosarcomas (PLBCL) present with skin lesions, other organs and systems are not involved. As CHOP courses are not high effective in PLBCL, we were the first to treat a patient with modified block therapy NHL BFM-90. A complete remission was achieved after the first course of polychemotherapy and was consolidated by two courses of treatment. Further follow-up is needed.

Aim. To evaluate efficacy of the protocol NHL BFM-90 in the treatment of adult anaplastic large cell lymphosarcoma (ALCL) ALK(+) and validity of addition of transplantation of autologous stem hemopoietic cells (ASHC) into first line treatment.Material and methods. We treated 13 patients with stage III-IV ALCL ALK(+). The age of the patients ranged from 17 to 44 years (median 26 years). The diagnosis was made using morphological histological, immunohistochemical methods with application of monoclonal antibodies to CD30, ALK, CD3, CD4, CD8, CD7, CD34, CD15, CD68, CD20, CD45RO, CD45RA. The patients were treated according to the protocol NHL BFM-90. ASHC was made in two patients with the disease stage IV.Results. We obtained a complete remission in 12 of 13 patients, one woman died of infectious complications in the beginning of the treatment, one man had early recurrence 45 days after the end of the treatment with lethal outcome and disease progression. Two patients at stage IV and poor prognosis had undergone ASHC transplantation. They are now in remission for 5 and 12 months.Conclusion. ALCL ALK(+) is characterized by an aggressive clinical course (11 of 13 patients had stage III-IV, high rate of extranodal lesions. Twelve patients achieved a complete remission, 11 (91.6%) of 12 patients are alive in observation median 27 months. We effectively used ASHC transplantation in the first-line treatment of 2 patients with stage IV of the disease and poor prognosis.