R-Dose-adjusted (DA) - EPOCH-21 Versus R-modified Non-Hodgkin Lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM)-90 Program (mNHL-BFM-90) and Autologous Stem Cells Transplantation (Auto-SCT) in DLBCL With Poor Prognosis

Purpose: to evaluate an efficacy of chemotherapy regimens R-DA-EPOCH-21 and R-mNHL-BFM-90 with and without autologous hematopoietic stem cells transplantation (auto-SCT) in newly diagnosed patients with DLBCL with intermediate and high risk.

Patients initially are randomized into 4 arms:

1. st arm R-DA-EPOCH-21
2. nd arm R-mNHL-BFM-90
3. rd arm R-DA-EPOCH-21 + auto-SCT
4. th arm of R-mNHL-BFM-90 + auto-SCT

Patients who achieved complete remission after 6 cycles of R-DA-EPOCH-21 or R-mNHL-BFM-90 immunochemotherapy continue to be under observation (1st and 2nd arms) or continue treatment with Rituximab + BCNU+Etoposid+Ara-C+Melphalan (R-BEAM) followed by auto-SCT (3rd and 4th arms). Patients who achieved partial remission after 6 cycles of R-DA-EPOCH-21 or R-mNHL-BFM-90 immunochemotherapy continue treatment with 2 cycles of Rituximab+Dexamethasone+Ara-C+Cisplatin (R-DHAP), continue to be under observation (1st and 2nd arms) or continue treatment with R-BEAM, followed by auto-SCT (3rd and 4th arms).

Eligibility Criteria:
Inclusion Criteria:

1. Newly diagnosed DLBCL,
2. No previous treatment with chemotherapy and/or radiation therapy of DLBCL
3. Presence of 2 or more signs of unfavorable prognosis (IPI 2-4)
4. Age 18-60 years.

Exclusion Criteria:

1. Transformation of mature cell lymphomas in DLBCL.
2. B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Hodgkin's lymphoma
3. B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma
4. DLBCL of central nervous system (CNS)
5. testicular DLBCL
6. Primary mediastinal large B-cell lymphoma
7. Pretreated DLBCL.
8. HIV-associated DLBCL
9. Congestive heart failure, unstable angina, severe cardiac arrhythmias and conduction disturbances, myocardial infarction.
10. Renal insufficiency (serum creatinine greater than 0.2 mmol/L) (except cases with specific kidney infiltration, urinary tract compression by tumor conglomerate or presence of uric acid nephropathy due to massive cytolysis syndrome).
11. Liver failure (except cases with liver tumor infiltration), acute hepatitis or active phase of chronic hepatitis B or C with serum bilirubin greater than 1.5 standards, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3 standards, prothrombin index less than 70%.
12. Severe pneumonia (except cases with specific lungs infiltration), accompanied by respiratory failure (dyspnea \> 30 in min., hypoxemia less than 70 mm Hg, when it is impossible to compensate situation in 2-3 days).
13. Life-threatening bleeding (gastrointestinal, intracranial), with exception of bleeding due to tumor infiltration of organs (stomach, intestines, uterus, etc.) and disseminated intravascular coagulation due to underlying disease complications after their successful conservative treatment.
14. Severe mental disorders (delusions, severe depressive syndrome and other manifestations of productive symptoms) not related with specific infiltration of central nervous system.
15. Decompensated diabetes.
16. Pregnancy.