Fludarabine and mitoxantrone: effective and well-tolerated salvage therapy in relapsed indolent lymphoproliferative...

Prior studies of the combination of fludarabine, mitoxantrone and dexamethasone have yielded high response rates but are associated with a significant risk of opportunistic infections, predominantly Pneumocystis Carinii pneumonia (PCP) requiring routine prophylaxis.

We evaluated the combination of fludarabine (25 mg/m2/day x 3) and mitoxantrone (10 mg/m2 x 1) without corticosteroids or PCP prophylaxis in 29 patients with relapsed or refractory indolent lymphoproliferative disorders; median age 56 years, 62% refractory to preceding chemotherapy.

A median of four cycles was administered without cumulative myelosuppression. Neutropenia <0.5 x 10(9/)l was seen in 16% of cycles. Infections complicated 10.4% of cycles. with impaired performance status (> or = ECOG 2) and increased age ( > 56 years) significant risk factors (P < or = 0.01). No cases of PCP were encountered. The response rate was 90%, median remission duration 11.9 months and the median survival 57 months. Peripheral blood progenitor cell mobilization was attempted in 11 patients and yielded > or = 2 x 10(6) CD34+ cells/kg in only 5 cases (45%).

High response rates can be attained with fludarabine and mitoxantrone in combination without corticosteroids, and routine PCP prophylaxis can safely be omitted. Peripheral blood progenitor collections are problematic in these heavily pretreated patients.