Salvage chemotherapy in follicular non-Hodgkin's lymphoma: focus on tolerability.

Follicular lymphoma (FL) is typically characterized by repeated remissions and relapses, and many patients receive a number of therapeutic interventions during their disease course. Although treatment options are evolving rapidly, stem cell transplantation offers a potentially favorable impact on survival. In general, many patients with FL are not eligible for this approach by virtue of age and/or comorbid disease. Salvage chemotherapy consequently remains the mainstay of treatment, being individualized according to disease and patient characteristics, goals of therapy, and patient preference. Many of the cytotoxic agents used in relapsed FL are highly myelotoxic, leading to significant morbidity and mortality, including febrile neutropenia, hemorrhage, and impaired quality of life. Nausea and vomiting can also be problematic, particularly with regimens incorporating carmustine, cisplatin, and high-dose cyclophosphamide. Other acute toxicities include mucositis, alopecia, extravasation injuries, and neurotoxicity. Late toxicities can also occur, sometimes months or even years after the administration of antineoplastic agents. Acute myeloid leukemias, myelodysplastic syndromes, or solid tumors can occur after chemotherapy with alkylating agents. The cardiotoxic profile of anthracycline antibiotics is well recognized, and several agents, including carmustine and cyclophosphamide, can cause lung injury. Persistent neurotoxicity, nephrotoxicity, ototoxicity, and vascular toxicity have also been reported in association with chemotherapeutic agents used in patients with relapsed FL. Novel therapeutic strategies might allow patients to achieve longer remissions, potentially reducing lifetime exposure to repeated cycles of chemotherapy and their attendant toxicities. These could include the use of more efficient preparative and purging approaches in the translantation setting or the administration of rituximab maintenance therapy after (immuno) chemotherapy induction or transplantation.