Early Treatment Stratification Based on PET Scan Response to Chemotherapy in Patients With Diffuse Large B-cell Lymphoma

The aim of the study is to evaluate the event free survival at three years in patients with diffuse large B-cell lymphoma with poor prognostic factors receiving R-MegaCHOP as induction therapy. Patients with positive PET after three cycles of R-MegaCHOP receive early salvage treatment with R-IFE and autologous stem cell transplantation. Patients with negative PET after three cycles of R-MegaCHOP are treated with three additional cycles of R-MegaCHOP without transplant.

In addition to the above:

* To evaluate the overall survival after three years.
* To determine the rate of global responses and complete remissions, uncertain and partial.
* To determine the duration of the complete response after the treatment termination.
* To carry out an exploratory follow up of the event free survival and the overall survival at 5 years.
* To evaluate the treatment toxicity according CTC criteria (version 3.0) of the National Cancer Institute (NCI).
* To asses the role of PET in the disease stage and response evaluation compared to CAT.
* To identify the predictable response factors after 6 cycles of treatment with R-MegaCHOP administrated every 21 days; or 3 cycles of R-MegaCHOP, followed by IFE+TAPH in patients with DLBCL of severe prognosis.
* To evaluate the therapeutic fulfillment of the R-MegaCHOP and R+IFE cycles of treatment and/or R-IFE in reference with delays with the cycles administration and reductions of the chemotherapy dose (planned dose administrated in the planned term).

Eligibility Criteria:
Inclusion Criteria:

1. follicular lymphoma grade III diagnosed patients, diffuse large B-cell lymphoma, histologically confirmed with CD20+
2. aged between 18 and 65 years. Patients aged from 65 to 70 years can be included according to the investigator's criteria regarding the patients' global health status and the absence of excluding comorbidity.
3. IPI adjusted to the age over 1 or a-IPI and beta2-microglobulin equal or higher than 3 mg/dl 3. Punctuation in the ECOG grade from 0 to 4
4. Life expectancy over 12 weeks
5. Written informed consent form 6. New diagnosed patient without any previous treatment

Exclusion Criteria:

1. Existence of severe cardiac, pulmonary, neurologic, psychiatric and metabolic diseases not caused by the lymphoma.
2. uncontrolled high blood pressure (diastolic pressure in rest \> 115 mmHg)
3. Altered hepatic function (bilirubin or AST/ALT superior or equal at 2 times the superior limit of normality) or renal (creatinine equal or superior at 1.5 times the superior limit of normality) not caused by the lymphoma.
4. other malignant neoplasias along the past 5 years, except skin tumors, excluded melanoma or carcinoma in situ of cervix
5. patients positive for HIV
6. patients with transformed follicular lymphoma
7. pregnant women or in nursing; women of childbearing age who do not use an adequate contraceptive method before being included in the study
8. ventricular ejection fraction inferior to 50%
9. patients with severe psychiatric diseases which can interfere with their ability for understanding the study (including alcoholism or drug addiction)