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Ann Janssens, Marc Boogaerts, Gregor VerhoefDepartment of Hematology, University Hospitals Leuven, Campus Gasthuisberg, Leuven, BelgiumAbstract: Fludarabine is an antineoplastic agent used in the treatment of hematological malignancies, particularly chronic lymphocytic leukemia (CLL) and indolent B-cell lymphoma. Because of its immunosuppressive effects, fludarabine has been added to reduced intensity conditioning regimens. The oral formulation of fludarabine has become widely available. Pharmacokinetic studies have shown that an oral dose of 40 mg/m2/d would provide systemic drug exposure similar to the standard intravenous (IV) dose of 25 mg/m2/d. The oral dose can be taken once daily without any dietary restrictions. Dose adjustments are mandatory in patients with renal impairment to avoid increased toxicity. Several noncomparative trials in previously untreated and treated patients with CLL have shown that treatment with the oral formulation demonstrates similar efficacy compared to historical control groups treated with the IV formulation. The tolerability profile of oral fludarabine seems similar to that of the IV formulation. Myelosuppression and infectious complications are the most frequently reported adverse events. Gastrointestinal toxicity is more frequent with the oral formulation, but is usually of mild or moderate severity. Although oral fludarabine makes treatment more convenient, health care workers must be aware of the compliance behavior of each patient. Keywords: CLL, treatment, oral fludarabine, intravenous fludarabine

Background Growth factors are frequently used to aid peripheral blood progenitor cell mobilization from bone marrow. This phase 2 study examined the efficacy and safety of pegfilgrastim for mobilizing peripheral blood progenitors cells for autologous transplantation.Design and Methods Patients with non-Hodgkin’s lymphoma received one cycle of mobilizing chemotherapy (ifosfamide, carboplatin and etoposide, ICE). Twenty-four hours later they were randomized, double-blind, to receive a single dose of pegfilgrastim 6 mg or 12 mg, or filgrastim 5 μg/kg/day (until the end of leukapheresis). Following leukapheresis (collection phase), patients rested or received one or two ‘salvage’ cycles of ICE. High-dose BEAM chemotherapy was then given before peripheral blood progenitor cell transplantation. The primary end-point was the patients’ mean yield of CD34+ cells/kg during the collection phase.Results Ninety patients were randomized and received a study drug; 63% completed the collection phase. The patients’ mean (95% CI) CD34+ cell harvest per leukapheresis was 0.8 (0.5–1.4), 0.8 (0.5–1.6) and 1.2 (0.7–2.0)×106 cells/kg for the pegfilgrastim 6 mg, pegfilgrastim 12 mg and filgrastim groups, respectively. Twenty (69%), 17 (59%) and 23 (72%) patients in these three groups achieved the targeted minimum harvest (≥2×106 cells/kg). The mean total harvests were 1.7, 1.4 and 2.2×106 cells/kg, respectively. Post-transplantation, the median days to absolute neutrophil count recovery (≥0.5×109/L) were 12, 11, and 11, respectively. Pegfilgrastim and filgrastim were generally well tolerated.Conclusions Pegfilgrastim (6 or 12 mg) was effective for mobilizing peripheral blood progenitors cells in patients with non-Hodgkin’s lymphoma. These data may aid the design of studies to clarify optimal dosing and leukapheresis with pegfilgrastim.