Fludarabine, mitoxantrone and dexamethasone (FND) in the treatment of indolent lymphoid malignancies

Abstract

Background: Indolent lymphomas are uncommon in the Chinese people and optimal treatment is undefined. We evaluated prospectively the combination of fludarabine, mitoxantrone and dexamethasone (FND), a regimen shown to be effective in the West for low-grade lymphomas, in the treatment of indolent lymphomas in this population. Patients and methods: There were 44 men and 20 women, with a median age of 61 (33 -72) years. The diagnosis included follicular lymphoma (FL) (n=28), chronic B cell leukemia (B-LPD) (n=l 6), mantle cell lymphoma (MCL)(n=4), marginal zone B cell lymphoma (MZBL) (n=4), Maltoma with diffuse component (n=8), andT cell lymphoma (n=4). A total of 28 cases (43%) were treated at diagnosis (Dx) while 36 cases (57%) at relapse. The FND regimen comprised fludarabine (25mg/m2/day x3), mitoxantrone (10mg/m2xl) and dexamethasone (20mg/day x5), given at monthly intervals for six courses. This was given on an outpatient basis with cotrimoxazole prophylaxis for pneumocystis infection. Results: Sixty cases were évaluable. The overall response rate was 70% with complete response (CR) and partial response (PR) rates of 57% and 13% respectively. Therapy was not completed in 15 cases (23%) because of infection (n=8) or rapid disease progression (n=7). A high CR rate was observed in the following disease subtypes: grade 1/2 FL at Dx (10/10,100%), T cell lymphoma (3/4,75%), MZBL (3/4,75%) and Maltoma (4/6,66%). Intermediate response rates (CR+PR) were seen in grade 1/2 FL at relapse (6/9, 66%) and in B-LPD (5/11, 56%). The response rates in patients previously treated with purine analogues and anthracycline containing regimens were 60% and 55% respectively. Diseases with low response rates included grade 3 FL (I/ 3,33%), MCL (1/4,25%) and transformed B-LPD (0/3,0%) Prolonged marrow suppression and septicemia (n= 12) occurred mainly in older patients (age>65, n=5) and heavily pretreated cases (>6 courses, n=6). Opportunistic infections included tuberculosis (TB) (n=4), cytomegalovirus gastritis (n=l) and systemic cryptococcosis (n=l). Hepatitis B carriers (n=7) were given prophylactic lamivudine and no reactivation occurred. At a median follow up time of 13.8 months, disease progression was observed in 6 responding cases (5PR, 1CR). Sixteen patients have died, 13 due to disease progression, one each from sepsis, cirrhosis and bronchogenic carcinoma. Conclusions: FND appears to be a safe and effective first-line and salvage treatment in a wide spectrum of indolent lymphoproliferative disease in Chinese patients. The high response rate in T-lineage disorder is encouraging. Owing to its immunosuppressive effects, prudent prophylaxis for opportunistic infections is required.