Plerixafor Is Highly Effective for the Mobilization of Autologous PBSC for Transplant in Children Failing to Mobilize by Conventional Means: International Experience with 40 Children From 19 Centers

Abstract 1931

Mobilization of peripheral blood stem cells (PBSC) for autologous transplant in children can be challenging especially in those with prior intensive chemotherapy and radiotherapy, and with increasing use of sequential high-dose therapy that requires high PBSC collection doses. Plerixafor is currently not licensed for use in children, but is approved for PBSC mobilization in adults. We present a series of 40 children from 19 centers worldwide who had PBSC mobilised with plerixafor off-licence, mostly on the North American or European Compassionate Use Programs. Thirteen of these cases were included in a series presented in abstract form at ASH 2010, and a further 6 were presented at EBMT 2011, and these cases are now presented with updated clinical data; the remaining 21 cases have not been presented elsewhere at the time of submission. Median age was 10 years (range 3 months–17 years); median weight was 31 kg (range 6–78 kg). Diagnoses were neuroblastoma (n=13), Ewing's sarcoma (n=10), medulloblastoma (n=5), lymphoma (n=5), PNET (n=4), multicentric Castleman's disease (n=1), Osteosarcoma (n=1) and Desmoblastic Small Round Cell Tumor (n=1). Most patients had received extensive multi-agent chemotherapy prior to plerixafor mobilization, and 13 had also received radiotherapy. For 7 patients, plerixafor had been introduced on a “rescue” basis in the course of the patient's first PBSC mobilization attempt, because of poor peripheral CD34+ counts predicting a high likelihood of mobilization failure without plerixafor use. The remaining 33 patients had undergone 45 prior failed conventional PBSC mobilization attempts: no apheresis in 31 cases; 8 were suboptimal (CD34+ dose < 2×10^6/kg); 5 procedures had yielded insufficient cells for planned sequential high-dose therapy. Plerixafor was used in 44 mobilization episodes (4 patients had undergone two mobilizations using plerixafor). In 29 cases, the drug was given after G-CSF 10 mcg/kg/day for 4 days, without prior mobilizing chemotherapy. In the remaining 15 cases, plerixafor was introduced to chemomobilization protocols at the time of initial neutrophil recovery, with exact protocols varying between centers. Three plerixafor mobilisation episodes were entirely unsuccessful (no apheresis); 10 episodes were suboptimal (CD34+ dose of <2×10^6/kg); 31 episodes (70%) were successful (>2×10^6/kg). For the 41 episodes where apheresis was undertaken, a median of 3.5×10^6/kg CD34+ cells (range 0.26–11.8) was collected in a median of 2 aphereses (range 1–5) after a median of 2 plerixafor doses (range 1–5). A total of 16 possible plerixafor toxicities were reported, all graded mild or moderate: these were injection site reactions (3), nausea (3), bone pain (3), vomiting (2), diarrhoea (2), insomnia (2) & headache(1). Seven patients were lost to follow-up after plerixafor due to transfer to other centers; of the remainder, 22 patients (67%) remain alive and 16 (48%) remain progression-free at a median of 9 months' follow-up post-plerixafor (range 3–63 months). Autologous PBSC transplant was performed in 27 patients & allograft in 1 patient. All transplanted patients achieved neutrophil engraftment (median of 11 days to neutrophils>1.0×10^9/litre; range 10–23 days). There was one case of secondary AML at >3 years post-autograft. Plerixafor is safe and highly effective in this difficult-to-mobilize patient group.