Good Efficacy of Single Dose PEG-Filgrastim in Enhancing the Mobilization of CD34+ Peripheral Blood Stem Cells (PBSC) in Aggressive Lymphoma Patients Treated with Cisplatin-Containing Regimens.

Background. Pegfilgrastim is a polyethylene glycol (PEG)-conjugated form of G-CSF in which filgrastim is bound covalently to a 20kDa PEG molecule; this formulation increases serum half-life of G-CSF due to decreased renal elimination. Following the subcutaneous injection of a 6 mg single dose of pegfilgrastim, serum levels of G-CSF are maintained over a period of 2 weeks. In patients with lymphoma, pegfilgrastim is as effective as filgrastim in shortening the time of neutropenia after cytotoxic chemotherapy; however, the ability of pegfilgrastim to mobilize stem cells after chemotherapy is poorly understood and the optimal mobilization strategy remains controversial.

Aims. We evaluate the efficacy of a single fixed 6 mg dose of pegfilgrastim after salvage therapy with cisplatin-containing chemotherapy regimens in mobilizing peripheral blood stem cells in aggressive lymphoma patients. Moreover the possibility of a sufficient collection of CD34+ PBSC (cell dose > 2,5 x10⁶/Kg) in a single procedure was tested.

Methods. Between July 2004 and July 2005 twenty two pretreated patients with aggressive lymphoma (8 Hodgkin’s lymphoma, 11 diffuse large B cell lymphoma, 3 anaplastic lymphoma) received salvage chemotherapy with cisplatin-based regimens: (R)-DHAP, dexametasone, cisplatin, cytarabine, or (R)-IPAD idarubicin, dexametasone, cisplatin, cytarabine, with or without Rituximab. A 6 mg single dose of pegfilgrastim was given from day +1 or +2 after chemotherapy completion. Duration of grade 4 neutropenia, adverse events, time to neutrophil and CD34+ cell recovery were recorded. Stem cell collection was started when the absolute number of CD34+ was not less than 20/μL. Leukapheresis was daily performed until the minimum target cell dose of 2.5 x 10 ⁶ CD34+ cells /kg was reached.

Results. Following the administration of either (R)-DHAP or (R)-IPAD regimens, 21/ 22 pts (95%) were able to harvest a median of 14,2 x 10 ⁶/Kg CD34+ cell (range 2,4– 45,8), after a median of 9 days from stimulation (range 8–12). A single apheresis procedure was sufficient to obtain a median of 14,8 x 10 ⁶/kg CD34+ cell (range 5,2–45,8) in 18/21 pts (86%) Grade 4 neutropenia was present in all pts with a median duration of 3 days (range 1–7). Pegfilgrastim determined mild bone pain as only adverse event. Seven patients underwent autologous bone marrow transplantation and all of them showed a rapid and sustained engraftment after high-dose chemotherapy.

Conclusions. In aggressive lymphoma patients a single dose of pegfilgrastim following chemotherapy completion was safe and highly effective in enhancing the mobilization of CD34+ PBSC. Stem cell collection was performed in a single procedure in most of patients (86%) obtaining a stem cell harvest of a median of 14,8 x 10⁶/Kg CD34+ cells. In 7 autologous bone marrow transplanted patients these results determined early engraftment and sustained hematological reconstitution.