DP060 | SAFETY AND EFFICACY OF ADDITION OF FILGRASTIM TO CD34+ CELL COLLECTION IN FOUR CASES OF SICKLE CELL DISEASE PATIENTS FOR GENOME EDITING

Sickle cell disease (SCD) is a genetic disorder characterized by abnormal hemoglobin (HbS), leading to chronic anemia and vaso-occlusive crises (VOCs), which can cause multi-organ damage. Current therapies like hydroxyurea (HU) and blood transfusions, alleviate symptoms but do not prevent complications. Hematopoietic stem cell transplantation (HSCT) remains the only curative option, though limited by donor availability and toxicity. CRISPR/Cas9 gene-editing targeting the BCL11A gene to increase fetal hemoglobin is becoming available as treatment for SCD. However, this approach requires at least 20x10^6 CD34+/kg cells, a challenging target in SCD patients due to the contraindication of standard G-CSF, which may trigger VOCs. In literature, only a few cases of mobilization of SCD using standard G-CSF are reported. We treated 4 patients with SCD (M/F: 3/1; age 21–32; 3 HbSS, 1 HbS/β+): 2 from Riyadh (SAU), 1 from Perugia (IT), and 1 from Pescara (IT). Median VOCs/year was 6. 3/4 patients were already on erythrocytapheresis (EEX). Italian patients were treated with HU (20–30 mg/kg). Treatment was authorized and supported in the pre-authorization phase by the Italian Drug Agency (AIFA) as part of the National Fund for Innovative Medicines. All patients underwent at least two CD34+ collections: the first with Plerixafor alone (0.24 mg/kg/day for 3 days). Collected CD34+ cells were insufficient for gene editing for all the patients: 6.18 x10^6/kg and 3.99x10^6/kg in Riyadh, 16.2 x10^6/kg and 7.9x10^6/kg in Italy. The last mobilization was performed with Plerixafor and off-label Filgrastim (with a specific request and dedicated informed consent). All patients received intensive EEX (HbS <20%) and antithrombotic prophylaxis during stimulation days. Filgrastim dose was 10 mcg/kg/day for 5 days (Riyadh, Perugia) and 5 mcg/kg/day for 7 days (Pescara). Final CD34+ collections were 33.1 x10^6/kg and 30.8x10^6/kg in Riyadh, 30.19x10^6/kg in Pescara, and 73.3x10^6/kg in Perugia. The percentage of increases were 436%, 672%, 84.6%, and 828%, respectively. All patients reached the theoretical threshold for gene editing. No pain crises occurred during treatment. Our findings suggest that Filgrastim, combined with Plerixafor and preceded by EEX and antithrombotic prophylaxis, may safely and effectively enhance CD34+ mobilization in SCD patients eligible to CRISPR/Cas9 gene-editing technology. Further large-scale studies are needed to confirm long-term safety and efficacy.