Fludarabine-containing chemotherapy for patients with previously untreated low-grade non-Hodgkin's lymphoma

Abstract

BackgroundThe clinical efficacy and safety of fludarabine combination chemotherapy was investigated for the treatment of previously untreated patients with low-grade (NHL).MethodsTwenty-five patients who were newly diagnosed as low-grade NHL were treated with fludarabine combination chemotherapy. Fludarabine combination regimens consisted of fludarabine, mitoxantrone and dexamethasone or fludarabine, cyclophosphamide and mitoxantrone with or without rituximab and repeated every 4 weeks.ResultsThe median age was 60 years (range, 35-77 years), with 13 of 25 patients (52%) ≥60 years of age. Seven of 25 patients (28%) with an intermediate risk follicular lymphoma international prognostic index (FLIPI) and 9 of 25 patients (36%) with a high risk FLIPI were enrolled in this study. The delivered median number of chemotherapy was six (range, 2-9 cycles). The overall response rate with fludarabine-based treatment was 88%, including 52% complete remission and 36% partial remission. During the median follow-up of 19 months, the estimated 2-year event-free survival was 63±10% (95% CI, 43-83) and the 2-year overall survival was 78±9% (95% CI, 60-96). Fludarabine combination chemotherapy was frequently associated with grade 3 or 4 neutropenia in 84% patients. However, neutropenic infection was observed in only one (4%) patient. Four patients (16%) showed grade 3 or more non-hematologic toxicities, such as acute coronary syndrome, intracranial hemorrhage, anaphylaxis and gastric cancer.ConclusionFludarabine-combination treatment was a highly active regimen with well toleration in untreated low-grade NHL.

Successful desensitization protocol for a patient with fludarabine anaphylaxis during hematopoietic transplantation

“…One study by Lee et al on fludarabine chemotherapy regimens for low‐grade non‐Hodgkin's lymphoma reported a patient who developed Grade 3 anaphylaxis with hypotension, rash, and fever 7 7 . As no viable alternative was available and skin testing could not be performed, our decision to pursue desensitization with a grade 3 reaction is in keeping with the recent American Academy of Allergy, Asthma & Immunology drug hypersensitivity guidelines 6 .…”

“…7 The patient did not undergo subsequent desensitization. 7 As no viable alternative was Note: Fludarabine concentration of 0.05 mg/ml, for a total goal dose of 61.25 mg fludarabine. The solution was prepared by diluting 61.5 mg of fludarabine (Teva Canada Limited, DIN 0228 3859, Lot#: 20E27KA) 25 mg/ml to a concentration of 0.05 mg/ml using preservative-free NaCl 0.9% (Baxter Limited, DIN: 0006 0208, Lot#: W1D08M0).…”

“…One study by Lee et al on fludarabine chemotherapy regimens for low-grade non-Hodgkin's lymphoma reported a patient who developed Grade 3 anaphylaxis with hypotension, rash, and fever. 7 The patient did not undergo subsequent desensitization. 7 As no viable alternative was Note: Fludarabine concentration of 0.05 mg/ml, for a total goal dose of 61.25 mg fludarabine.…”

“…The lack of literature on fludarabine desensitization is likely due to the rarity of reported anaphylaxis. One study by Lee et al on fludarabine chemotherapy regimens for low‐grade non‐Hodgkin's lymphoma reported a patient who developed Grade 3 anaphylaxis with hypotension, rash, and fever 7 7 .…”

Successful Transplantation of Kidney Allografts in Sensitized Rats After Syngeneic Hematopoietic Stem Cell Transplantation and Fludarabine

“…Fludarabine has been used in the treatment of hematological malignancies. Alone or in combination with other drugs, it is effective in the treatment of B cell chronic lymphocytic leukemia and low‐grade non‐Hodgkin's lymphoma . Fludarabine may affect B cell receptor signaling and costimulatory molecules, leading to multiple signals for apoptosis and cell clearance .…”