PEG-Filgrastim for Autologous Peripheral CD34+ STEM CELL Collection in Pediatric Oncological PATIENTS: A PHASE II STUDY.

Pegfilgrastim (Peg-f) is the pegylated long-acting formulation of filgrastim that allows recovery from chemotherapy-induced neutropenia by single-shot administration. Data on adults show that Peg-f is safe and efficacy also in CD34+ peripheral blood stem cell collection. From May 2007 to July 2008, Peg-f was administered to 34 consecutive patients from 4 Italian pediatric centres at a dosage of 100 ug/kg (max 6 mg) for PBSC purposes. They were 21 male and 13 female, median age at diagnosis of 10 years (range 3–18), affected by solid tumour, 30 (Ewing, 9; Medulloblastoma, 5; Neuroblastoma, 5; brain tumours, 4; other, 7), acute lymphoblastic leukaemia or non-Hodgkin lymphoma, 4. The remission status at PBSC was: CR 8 (24%), VGPR 5 (15%), PR 19 (56%), SD or not known 2 (6%). The median weight was 35.5 kg (range 13.5–86) and the median number of planned infusion was 1, range 1–3. Different regimens of mobilizing chemotherapy were used, etoposide, cyclophosphamide and ifosphamide being the most frequent drugs administered. The median time to first PBSC was 10 days, range 6–15. The least threshold for CD34+ collection (20 cell/ul) was obtained in 28 of 34 patients (82%), the median value of CD34+ peak being 140 (range 20–1988). Successful PBSC was obtained in 27 patients (79%) because one very low weight child failed it for suboptimal vascular access. Sixteen of 27 patients (59%) achieved the target PBSC collection with 1 leukapheresis whilst 10 patients required a second leukapheresis. The median collection yield was 8 (range 1.9–116) and 2.45 (range 1–6) CD34+ x 10⁶/kg) for the first and second leukapheresis, respectively. No Peg-f related adverse effects were reported. So far, 15 of 27 patients (56%) underwent a first autologous transplant whilst 4 and 1 underwent a second and third transplant, respectively. The median time from PBSC to first transplant was 64 days (range 10–154) and the median value of CD34+ x 10⁶/kg infused was 7 (range 3–299). Different conditioning regimen were used, myeloablative doses of busulfan, thiothepa, melphalan, and etoposide being the drugs most frequently used. After a median f-up of 29 days from first transplant (range 16–176), all patients achieved a PMN count > 0.5 x 10⁹/l in a median time of 13 days (range 5–23) whilst 14 and 12 achieved a transfusion-unsupported PLT count > 20 and > 50 x 10⁹/l in a median time of 13 (range 5–23) and 15 days (range 12–36), respectively. Prophylactic post-transplant G-CSF was used in 7 of 15 patients (47%) for a median time of 7 days (range 1–11). All 5 patients who performed a second or third transplant successfully engrafted for PMN and PLT. All 15 transplanted patients were alive at latest f-up. We conclude that Peg-f single-shot CD34+ mobilisation is safe and efficacy also in pediatric patients. Further prospective studies are needed to investigate the non-inferiority or superiority of Peg-f vs. filgrastim in PBSC.