Mantle Cell Lymphoma (MCL) is a malignancy with a poor response to treatment and with a median survival of 2- 4 years since diagnosis. Although histology is similar to that of an indolent lymphoma, MCL is currently considered an aggressive tumour. Few prospective therapeutic trials have been reported in MCL, and results are difficult to interpret due to treatment heterogeneity. It is known that standard chemotherapy for other clinically aggressive lymphomas yields poor results. Recently, better results have been communicated with intense induction chemotherapy treatments or consolidating the response with high dose chemotherapy with stem cell support. Keeping in mind these considerations, we will use and intensive induction treatment with Hyper-CVAD/MTX-AraC associated with anti-CD20 in order to increase the overall response rate followed by consolidation treatment with Ibritumomab -tiuxetan (Zevalin) with the aim of eradicate the minimal residual disease, responsible of relapse.

Study Design:

• The Patients will receive 6 cycles of induction chemotherapy as follows: Anti-CD20/Hyper -CVAD chemotherapy will be alternated with anti-CD20 +MTX/Ara-C chemotherapy. After 4 cycles (2 x2), response will be evaluated. If response (complete or partial) is observed, 2 additional cycles will be administrated. If less than a partial response is observed, the patient will be out of the study.
• Consolidation treatment will be a single dose of Y90Ibritumomab -Tiuxetan (Zevalin) will be administered after 12 weeks after completion of induction chemotherapy. The initial dose of Zevalin will be 0.3 mCi/kg, to be further escalated to 0.4 mCi/Kg if unacceptable toxicity does not occur.

Inclusion Criteria:

• All histologic MCL subtypes (WHO classification)
• Age between 18 and 70 years old
• Performance status 0 to 2 (ECOG)
• Cardiac ejection fraction >50%
• Adequate organ (hepatic, cardiac and renal) and marrow function: Hb> 10g/dl, neutrophil counts> 1500/ µl, platelet> 100000/ µl. Creatinine < 2,5xULN, bilirubin, AST or ALT<2,5xULN.
• For Y90-ibritumomab tiuxetan administration: Bone Marrow Infiltration by lymphoma cells < than 25% ; platelet count >100,000/µl and neutrophil counts >1500/µl
• Informed consent should be obtained

Exclusion Criteria:

• Ann Arbor stages I or II without B symptoms or bulky disease (>10 cm).
• Previous chemotherapy or radiotherapy treatment.
• Uncontrolled current illness: Hepatic, renal, cardiovascular, neurological or metabolic illness.
• Symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia.
• HIV, HBV or HCV positive serology.
• Limitation of the patient´s ability to comply with the treatment or follow-up protocol.
• Men and women with reproductive potential who are not using effective contraceptive methods during and at least 12 months after the end of the study
• Acute or chronic active infection.
• Known hypersensitivity to some of the drugs or other related compounds
• No informed consent obtained