This Phase II study randomized R-ACVBP and R-CHOP as induction treatment in patients from 18 to 59 with DLBCL CD20+ lymphoma and 2 or 3 adverse prognostic factors of the age-adjusted IPI. The consolidation treatment is allocated according to the response to induction treatment assessed by PET after the 2nd and 4th induction cycles.

1) Induction Arm A: 4 cycles of R-ACVBP, 2 weeks interval. After the 3rd cycle, if PET 2+ (fixing), collection of peripheral blood stem cell progenitors will be organized at the time of hematological recovery under support with G-CSF.

The consolidation treatment will depend on results of PET evaluation after cycle 2 (PET2) and cycle 4 (PET4).

• Consolidation 1A (in case of PET 2- PET 4 -):

  • High-dose Methotrexate with folinic acid rescue; 2 cycles spaced out 14 days.
  • Rituximab-Ifosfamide-Etoposide : 4 cycles spaced out 14 days
  • Cytarabine sub-cutaneous, during 4 days; 2 cycles spaced out 14 days.

• Consolidation 2 A (in case of PET 2+ PET4 -):

  • 2 cycles high-dose Methotrexate with folinic acid rescue
  • High dose with Z- BEAM conditioning regimen followed by autologous transplant.

• Salvage(in case of PET 4 +):

The patient will be treated with a salvage regimen, after a biopsy of the residual mass whenever possible.

2) Induction arm B: 4 cycles of R-CHOP, 2 weeks interval. After the 3rd cycle, if PET 2+ (fixing), collection of peripheral blood stem cell progenitors will be organized at the time of hematological recovery under support with G-CSF.

The consolidation treatment will depend on results of PET evaluation after cycle 2 (PET2) and cycle 4 (PET4).

• Consolidation 1B(in case of PET 2- PET 4 -):

  4 additional cycles of R-CHOP, 2-weeks interval

• Consolidation 2 B(in case of PET 2+ PET 4 -):

  • 2 cycles high-dose Methotrexate with folinic acid rescue
  • High dose with Z- BEAM conditioning regimen followed by autologous transplant

• Salvage(in case of PET 4 +):

The patient will be treated with a salvage regimen, after a biopsy of the residual mass whenever possible

Inclusion Criteria:

• Patient with histologically proven CD20+ diffuse large B-cell lymphoma (WHO classification).
• Age from18 to 59 years, eligible for transplant.
• Patient not previously treated.
• Baseline FDG-PET Scan (PET0) performed before any treatment with at least one hypermetabolic lesion.
• Index prognostic factors (IPI) 2 or 3.
• With a minimum life expectancy of 3 months.
• Negative HIV, HBV and HCV serologies £ 4 weeks (except after vaccination).
• Having previously signed a written informed consent.

Exclusion Criteria:

• Any other histological type of lymphoma.
• Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included.
• Central nervous system or meningeal involvement by lymphoma.
• Contra-indication to any drug contained in the chemotherapy regimens.
• Poor renal function (creatinin level >150 mmol/l), poor hepatic function (total bilirubin level >30 mmol/l, transaminases >2.5 maximum normal level) unless these abnormalities are related to the lymphoma.
• Poor bone marrow reserve as defined by neutrophils <1.5 G/l or platelets <100 G/l, unless related to bone marrow infiltration.
• Any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ)cervical carcinoma.
• Any serious active disease (according to the investigator's decision).
• Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy.
• Pregnant or lactating women or women of childbearing potential not currently practicing an adequate method of contraception
• Adult patient under tutelage.
• Impossibility to performed a baseline PET scan (PET0) before randomization and treatment beginning