The purpose of this study is to determine whether Bendamustine in combination with Etoposide, Cytarabine and Melphalan (BeEAM) are effective as conditioning followed by ASCT in patients with aggressive lymphoma.

BCNU (carmustine is a nitrosurea alkylating agent used for many years in the conditioning of patients with lymphoma however this drug is hardly available in some countries in Europe, moreover to improve conditioning regimens in autologous stem cell transplant is important because the anti-tumoral effect of high dose therapy are responsible for this procedure efficacy. Although for many years few advances have been achieved in this area now new drugs can be tested in these patients.

Bendamustine is a unique cytotoxic agent with structural similarities to alkylating agents and antimetabolites, but which is non-cross-resistant with alkylating agents and other drugs in vitro and in the clinic. Early clinical studies conducted in the German Democratic Republic more than 30 years ago suggested promising activity in indolent non-Hodgkin's lymphoma (NHL). Two North American trials reported responses in more than 70% of patients with chemotherapy- and rituximab-refractory disease, suggesting that bendamustine may be the most effective drug available for this patient population. Response rates of 90% to 92%, with complete remission in 55% to 60%, have been reported in patients with follicular and mantle-cell lymphoma with the combination of bendamustine and rituximab.(Cheson 2009) Leone et all have recently reported results on the characterization of the mechanisms of action of bendamustine and its comparison with structurally related compounds as chlorambucil and phosphoramide mustard have demonstrated that bendamustine displays a distinct mechanisms of action including activation of DNA-damage stress response and apoptosis, inhibition of mitotic checkpoints, and induction of mitotic catastrophe. Also bendamustine activates a base excision DNA repair pathway rather than an alkyltransferase DNA repair mechanism.

These data suggest that bendamustine possesses mechanistic features that differentiate it from other alkylating agents and makes this old new drug an attractive one to combine with other agents in the conditioning transplant setting (Leone 2008).

Inclusion Criteria:

1. Patients being able to meet all requirements of the clinical trial, according to the investigator's criteria,

2. Patient giving voluntarily written informed consent before performing any essay test that is not part of routine care of patients.

3. Age >o=18 years and >0=70 years

4. Candidate for chemotherapy (QT) at high doses and ASCT

   1. Histologically confirmed aNHL:
   2. Patients with DLBCL or grade 3 b Follicular lymphoma or PTCL (including anaplastic ALK +) in sensitive relapse, so, in second complete or partial response, after a minimum of 2 cycles of the rescue regimen.
   3. Patients with DLBCL or grade 3 b Follicular lymphoma or PTCL (including anaplastic ALK +) in first complete or partial response, if more than one treatment line have been required to reach this first complete or partial response.
   4. Transformed B cell lymphoma in first CR
   5. Patients with PTCL (other than anaplastic ALK +) in first CR

5. Performance status (ECOG) <0=2.

6. Adequate renal, hepatic, and bone marrow function (assessed < 14 days before initiation of the study treatment):

   1. Neutrophil count <o=1.5 x 109/L
   2. Platelet count <o=100 x 109/L
   3. Haemoglobin <o=8.0 g/dL
   4. Creatinine serum >o=1,5 x ULN mg/dl
   5. Serum bilirubin <o=1.5 x ULN and alkaline phosphatase <o=2.5 x ULN
   6. AST, ALT <o=2.5 x ULN (<o=5 x ULN in case of liver metastasis).

7. Adequate pulmonary function: forced expiratory volume at 1 second > 65% of predicted or a diffusing capacity of the lung for CO >o=50%.

8. Cardiac ejection fraction or greater than 50% by echocardiogram or FEVI.

9. A woman capable of gestation (see definition below) should:

   • Have two medically supervised negative pregnancy test (minimum sensitivity of 25 mIU / ml) before starting study therapy (the first pregnancy test should be completed in 10 to 14 days prior to initiating bendamustine and the latter pregnancy test 24 hours before the start of this drug).
   • Commit to a continued abstinence of heterosexual relationship or agree to use reliable contraception without interruption, 28 days before starting the study therapy, during the study therapy and for 28 days after stopping therapy study.

A woman capable of gestation is defined as sexually mature woman who:

1. has not undergone hysterectomy or bilateral oophorectomy and
2. is not naturally postmenopausal (amenorrhea as a result of cancer treatment does not rule the reproductive potential) for at least 24 consecutive months (i.e., menses at any time during the previous 24 consecutive months).

Exclusion Criteria:

1. Impossibility of collecting, via apheresis, a number of CD34+ cells >o=2 x 106/kg

2. To receive any of the following treatments in the 28 days before the start the study treatment:

   i.chemotherapeutic or antitumor agents ii.radiation therapy, except in limited fields, to a maximum dose of \