L-Asparaginase in the Treatment of Relapsing Nasal/Nasal Type NK-T-Cell Lymphoma.

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. Recently some papers from China and Japan, (

We used this drug in 3 french centers to treat 7 patients with relapsed nasal/nasal type NK-T-cell lymphoma.

There were 4 men and 3 women, median age was 52 (39 to 81), the primary site of disease was the nasal cavity in 3 patients, the nasopharynx in 2, the gastrointestinal tract in 1 and the bone marrow in 1. Pathological diagnosis was confirmed by biopsy, showing typical aspect of necrosis and angioinvasion. Tumoral cells were usually CD20 negative, SCD3 positive, CD56 positive. EBV was found by in situ hybridisation in all but one case.

When L-asparaginase was given 5 patients were refractory to CHOP and/or DHAP regimen, 5 patients were in stage IV with bone marrow involvment (n=2), cerebral involvment (n=2), gastrointestinal tract involvment (n=1). Hemophagocytosis was seen in 3 patients with typical biological anomalies.

L-asparaginase 6000 UI / m2 (1 to 3 courses) was given for 5 to 10 days associated with Dexamethasone 40 mg for 4 days (n=4), methotrexate 3 gr/m2 (n=1) or velbe 6 mg (n=1). 2 patients who had a severe anaphylactic reaction with L-asparaginase received further courses of PEG-asparaginase.

Treatment efficacy was evident in all patients with 4 patients in complete remission (CR) and 3 patients in partial remission (PR) after treatment with L-asparaginase. 2 patients died, one of acute GVH after allotransplantation and a second 1 month after the second course of L-asparaginase, probably of pulmonary embolism. Apart from this case toxicity related to L-asparaginase was mild, mainly brief leucopenia and elevation of alanine aminotransferase. With antithrombine III transfusions when its level was below 60% no other thrombotic event was noted.

5 patients are still alive with a median follow-up of 7 months (3 to 13), 4 patients are in persistent CR, 2 had received high dose therapy with autologous stem cell transplant.

The efficacy of L-asparaginase to treat nasal and nasal type NK-T-cell lymphoma must be known because of the very poor prognosis of relapsing patients with conventionnal chemotherapy. Prospective studies using L-asparaginase for de novo patients are warranted.