Single Center, Inpatient Pediatric Experience of Autologous Collections Using Pre-Collection CD34 Rate of Rise for Gene-Modified Products for Hemoglobinopathies

Modified autologous stem cell gene therapy products has shown transformative potential for treating sickle cell disease (SCD) and transfusion dependent thalassemia (TDT) who lack a matched sibling donor and eliminate the risk of graft versus host disease associated with allogeneic transplantation. One challenge with this approach is optimizing stem cell collections to ensure drug dose can be made in the setting of manufacturing inefficiencies. We describe our center's collection protocol and provide CD34 count rate of rise analysis following plerixafor mobilization in the inpatient pediatric setting. All subjects were collected on the inpatient ward. For TDT subjects, the administration of G-CSF 10 µg/kg/day SQ from Days 1-7 and plerixafor 0.24 mg/kg/day SQ at 0400 on Days 5-7 (about 4-5 hours prior to the start of apheresis). All apheresis collections began around 0800. For the SCD subject, red cell exchanges occurred every 3 weeks and the day prior to collection with a goal of hemoglobin S of 10-15% by electrophoresis (minimum of 3 exchanges prior to collection). For SCD subjects, only plerixafor was utilized on Days 1-3) at 0400 prior to apheresis. CD34 counts were drawn at baseline, at 0400 prior to plerixafor, and immediately prior to the start of apheresis. Each collection day lasted 7-8 hours (Days 1 and 2) and 4-5 hours (Day 3 for backup dose). As expected, young, pediatric subjects mobilize stem cells well. All patients tolerated mobilization without complications during or after apheresis. Subject 1 had two collections within 35 days of each other which may represent why collection 1.2 has lower absolute CD34+ counts than collection 1.1. This suggest allowing more time between collection cycles regardless of previous collection CD34 dose. Subject 2 underwent one collection cycle with excellent CD34 doses. Interestingly, there was a blunted rate of raise of CD34 on Day 2 but had similar CD34 doses collected suggesting a potential limitation apheresis collection capacity in robust mobilizers. Our single SCD patient had the lowest absolute CD34+ mobilization levels which correlates with historical data that demonstrate sickle cell patients as poor mobilizers likely due to chronic hematopoietic stress and limitations in single agent plerixafor as their sole mobilizing agent. Taken together, children responded well our current mobilization protocol, and no safety concerns were noted. There is a robust increase in mobilized CD34+ cells 4 hours after plerixafor dose demonstrated by the rate of rise calculation regardless of disease state, however, there is variation between days within a cycle. More data is needed to better understand if the rate of rise of CD34 counts can be utilized as a metric to predict mobilization efficacy and need for additional collection days or cycles.