Safety, Tolerability and Monitoring of Long-Term G-CSF Compassionate Use in ALS Patients (P3.181)

Objectives: Long-term compassionate use of granulocyte-colony-stimulating factor (G-CSF, filgrastim) in ALS patients. Background: G-CSF is a long-term established and safe hematopoietic growth factor that may potentially compensate rapid neuronal loss in ALS patients by neuroprotection, neurogenesis and immunomodulation. Although animal models seemed promising, pilot clinical trials were inconclusive. Relevant clinical improvement might have been missed due to inadequate dosing, and far too short duration of treatment and follow up. Bone marrow stem cells are directly involved in G-CSF treatment; their differentiation markers may serve as additional biomarkers and help understand the mode of action. Methods: 23 ALS patients (15m, 8f, mean ALS-FRS-r at start 36.75) were treated with G-CSF plus standard therapy after informed consent in an outpatient regimen. Application modes were individually adapted (150-720 MioIU/month s.c.). Monthly visits with ALSFRS-r, clinical chemistry, blood smears and bone marrow mobilization parameters were performed, followed by cerebral MRI and neurophysiological measurements on a 3-monthly basis throughout the long-term intervention up to 5 yrs. Results: Safety and compliance were excellent; we found no unexpected changes in blood smears. G-CSF was well tolerated, although acceptable mild or moderate bone pain was frequently reported. G-CSF resulted in effective hematopoietic stem cell mobilization (increase in CD34+ and CD34+38- cells). We found bone marrow colony forming capacity with G-CSF treatment to be associated to overall survival (OS). In retrospective analysis a significantly lower ALS progression rate (p<0.0001) and a clinically relevant prolongation of OS (p<0.0001) were observed in long-term G-CSF treated ALS patients compared to the current PRO-ACT database. Without respect to dosage, median OS since G-CSF treatment initiation was 28,5 months. Conclusions: Long-term administration of G-CSF in ALS patients is safe, well tolerated and feasible. Data are very robust; a prospective clinical trial is urgently needed. Acknowledgements: BMBF GO-BIO, BMBF MND Network Germany, PROACT-Database USA Disclosure: Dr. Johannesen has nothing to disclose. Dr. Khomenko has nothing to disclose. Dr. Baldaranov has nothing to disclose. Dr. Grimm has nothing to disclose. Dr. Kobor has nothing to disclose. Dr. Grassinger has nothing to disclose. Dr. Klatt has nothing to disclose. Dr. Kammermaier has nothing to disclose. Dr. Bruun has nothing to disclose. Dr. Kassubek has received personal compensation for activities with UCB Pharma, Boehringer Ingelheim, GlaxoSmithKline, Merz Pharmaceuticals, and Hoffman-La Roche as an adviser and/or consultant. Dr. Schuirer has nothing to disclose. Dr. Ludolph has nothing to disclose. Dr. Schulte-Mattler has nothing to disclose. Dr. Premont-Schwarz has nothing to disclose. Dr. Schneider has nothing to disclose. Dr. Deppe has nothing to disclose. Dr. Bogdahn has nothing to disclose.