Nasal/nasal type NK-T-cell lymphoma is a rare and severe type of non-Hodgkin's lymphoma (NHL) more frequent in Asia than in western countries. When localised, radiotherapy seems to be the best treatment. When radiotherapy cannot be used because of dissemination or relapse, chemotherapy protocols used for other types of NHL give poor results and survival is poor. Recently papers from China and Japan reported the efficacy of a drug: l-asparaginase, usually used to treat acute lymphoblastic leukemia. In vitro a selective apoptosis of NK-cell tumours by l-asparaginase was shown on tumour cell lines and samples.

The investigators propose a phase II protocol for patients with refractory or relapsing nasal/nasal type NK-T-cell lymphoma using a regimen combining l-asparaginase, methotrexate and dexamethasone. Biological studies will be conducted trying to find factors which could predict responses to this chemotherapy.

Since january 2009, the study concerns all patients with nasal/nasal type NK-T-cell lymphoma who have not received asparaginase before.

Primary Objective:

• Determine the overall and complete response rate

Secondary Objectives:

• To evaluate survival without progression
• To evaluate total survival.
• To evaluate the tolerance and the side effects of the treatment.
• To evaluate the duration and the mode of hospitalization of the patients treated by this therapeutic association.
• To constitute a bank of biological samples - serum, tumoral, ADN, ARN to allow prognostic studies implying virus EBV, p53, CD94, C-kit and asparagine synthetase gene in order to better understand the mechanisms of the cancerogenesis of this variety of cytotoxic LNH and to identify the predictive factors of response to the asparaginase.

Sampling:

For each patient included in the protocol, the following sampling will be carried out with the diagnosis:

• Biopsy,
• Medullary biopsy
• Medullary aspiration
• blood: 3 tubes of 7 ml on EDTA and 3 tubs of 7 ml with heparin

Treatment:

All the patients included will receive three cures separated by 3 weeks (J1, J22, J43):

• J1: Methotrexate 3 gr/m2
• J2, J4, J6 and J8: Kidrolase® 6000 u/m2
• J1 with J4: Dexamethasone 40 mg (20 mg if age > 70 years)

Inclusion Criteria:

Patients with relapsing/refractory T-NK/NK lymphoma:

• Ages 18 years and above
• Patients must have a diagnosis of NK-cell (or T-NK) non-Hodgkin's lymphoma, nasal or nasal-type.
• Stage I, II, III, or IV disease
• Creatinine less than 3 x upper limit of normal (ULN)
• Able to give informed consent
• No prior treatment with asparaginase

Patients with T-NK/NK lymphoma (de novo patients ):

• Ages 18 years and above
• Patients must have a diagnosis of NK-cell (or T-NK) non-Hodgkin's lymphoma, nasal or nasal-type.
• Stage I, II, III, or IV disease
• Creatinine less than 3 x upper limit of normal (ULN)
• Able to give informed consent
• no prior chemotherapy or radiotherapy

Exclusion Criteria:

• Patients who are pregnant or nursing
• Any factor which might limit the patient's ability to provide informed consent
• Liver insufficiency
• Evolutive thrombosis