• Event free survival (event = progressive disease or relapse or second malignancy or death from any cause)
  

• Survival
  
• long term toxicity (cardiotoxicity, impaired fertility, secondary malignancy)
  

Group B: Randomized trial with factorial design. The 4 treatment arms are standard LMB89 therapy B, reduction of cyclophosphamide (CPM) in COPADM2, deletion of COPADM3, both reduction and deletion. Randomization occurs following COPADM1 and is stratified for national group, histology (large cell; small non cleaved cell) and stage (Murphy I orII; Murphy III+LDH<2N; Murphy III+LDH>2N or Murphy IV).

The primary analysis questions are whether reducing CPM dose in COPADM2 results in a smaller long-term EFS whether omitting COPADM3 results in a smaller long-term EFS

Group C: Randomized trial. The 2 treatment arms are standard LMB89 therapy C versus reduction of CYVE + deletion of the last 3 maintenance courses. Randomization occurs following COPADM2 and is stratified for national group, histology (large cell; small non cleaved cell) and CNS disease.

The primary analysis question is whether reducing CYVE and omitting the last 3 maintenance courses result in a smaller long-term EFS than standard LMB 89 treatment C

Inclusion Criteria:

• Newly diagnosed B lineage non-Hodgkin's lymphoma with Revised European American Lymphoma (REAL) II 9 (diffuse large cell lymphoma), 10 (Burkitt's lymphoma), or 11 (high grade B cell lymphoma, Burkitt's like) or bone marrow > 5% L3 blasts.
• Pre treatment imaging studies adequate to document Murphy disease stage
• Group B and C patients are eligible for randomization (Therapy stratification by group : Group A=completely resected stage I or completely resected abdominal stage II lesions, Group B= All cases not eligible for Group A or Group C, Group C= Any CNS involvement and/or bone marrow involvement ³ 25% blasts)
• Patients should be available for a minimum follow up of 36 months
• Informed consent prior to study entry

Exclusion Criteria:

• Anaplastic large cell Ki 1 positive lymphomas
• Previous chemotherapy.
• Congenital immunodeficiency
• Prior organ transplantation
• Previous malignancy of any type
• Known HIV positivity