FLUDARABINE THERAPY IN IMMUNOCYTOMA AND OTHER LOW-GRADE NON-HODGKINS-LYMPHOMAS

Fifteen low-grade non-Hodgkin's lymphomas (LGNHL) received Fludarabine (FLU) at a dosage of 30 mg/sqm daily, for 5 days, every 4 weeks, for a total of 6 cycles. The histotypes were: 5 lymphoplasmacytic-lymphopl asmacytoid, 5 lymphocytic, 3 centroblastic-centrocytic follicular, 1 m ycosis fungoides, 1 lymphocytic-immunoblastic. All patients were in st age IV with marrow involvement. Five cases (3 immunocytomas) were trea ted at diagnosis, 2 with marrow residual disease after a previous firs t line conventional therapy, 3 in relapse and 5 with refractory diseas e. Eight out of twelve evaluable patients were responsive to the treat ment (66%); 3 reached CR (25%) and 5 PR (42%); 4 cases (33%) were not responsive. The therapeutic outcome was strictly correlated to the dis ease status and the disease extent but not, in pretreated patients, wi th the number of prior chemotherapy regimens; in fact previously untre ated and refractory patients showed a quite different response rate (4 /4 vs 0/3 response) and both patients treated for minimal marrow disea se after a previous therapeutic line reached CR. The best results were obtained in follicular centroblastic-centrocytic lymphoma (2/3 CR), i n immunocytoma (4/5 PR) and in lymphocytic lymphoma (2/3 responses). T he median response length and survival were 14 and 20 months, respecti vely. Besides the three not evaluable cases five additional patients d ied for disease progression (4) and infection not correlated to the tr eatment (1). Seven patients are alive. Toxic effects of treatment were not negligible and included myelotoxicity and possibly a neurologic s yndrome characterized by progressive mental deterioration, psycomotor restlessness, worsening mental confusion, coma and death, without foca l signs at neurologic examination (in two patients treated for refract ory mycosis fungoides and lymphocytic lymphoma). A case of sudden deat h was also recorded. In conclusion FLU is an effective drug for LG-NHL , at least for follicular centroblastic-centrocytic, lymphocytic lymph oma and immunocytoma, with the best results reached in untreated and r elapsed patients or in cases characterized by minimal residual disease after a previous treatment. On the contrary the drug is not likely to be successful with refractory patients. Moreover, in our experience t he FLU toxic effects appear remarkable, expecially on bone marrow, CNS and possibly heart.