Fludarabine is an Effective Agent in Immunocytic Lymphoma

Abstract

Background: Fludarabine monophosphate is a new adenine nucleoside analogue with promising efficacy in Waldenström’s macroglobulinemia with response rates of 31-45% in previously treated and up to 100% in previously untreated patients. Patients and Methods: In this paper we report on the clinical experience with fludarabine and its side effects in 9 patients with advanced or refractory immunocytic lymphoma including 5 patients with Waldenström’s macroglobulinemia. Fludarabine was administered at a dosage of 25 mg/m2 daily for 5 days as a 30-minute, intravenous infusion. This course was repeated every 5th week. Results: 1/9 patients achieved complete remission, and 6/9 achieved partial remission (PR); 1/9 had stable disease and 1/9 was progressive. The median remission duration until relapse or death was 7.4 months. Most responses to fludarabine occurred within 2 treatment courses. Major toxic effects included lethal infections in 2 patients. Both patients were in PR at time of developing infections, one Pneumocystis carinii pneumonia and one septicemia. The occurrence of even opportunistic infections may be due not only to hypogammaglobulinemia or fludarabine-induced granulocytopenia, but also to a remarkable decrease of CD4+ cells during fludarabine therapy. Conclusion: It is concluded that fludarabine is an effective agent in patients with advanced immunocytic lymphoma. However, fludarabine has a remarkable suppres-sive effect on T-lymphocytes, in particular on CD4+ lymphocytes, especially in pre-treated patients.

Waldenström macroglobulinaemia

“…Patients with WM have baseline immunosuppression because of low levels of uninvolved immunoglobulins and treatment‐related granulocytopenia. Nucleoside analogues reduce levels of circulating CD4 + T cells, increasing the risk of opportunistic infections (Fenchel et al , 1994; Wong et al , 2001), including cryptococcal meningitis (Costa et al , 1998) and viral enteric infection (Bjorkholm et al , 1995). Also, there have been reports of post‐transplant lymphoproliferative disorders (Niesvizky et al , 1999).…”

Waldenström macroglobulinemia: A review of therapy

“…The suppressive effect on T lymphocytes results in impaired cell-mediated immunity, and consequently unusual infections can be seen. In a study of only 9 patients, 1 patient died of Pneumocystis carinii pneumonia and 1 died of sepsis [36]. In 1 patient, massive astrovirus enteric infection developed after 3 cycles of fludarabine and responded to cessation of fludarabine and the intravenous administration of immunoglobulin [37].…”