Bone marrow harvesting from paediatric patients undergoing haematopoietic stem cell gene therapy

Area of Science:

• Hematology
• Pediatric Oncology
• Gene Therapy

Background:

• Autologous haematopoietic stem progenitor cells (HSPC) are crucial for ex vivo gene therapy (GT) in inherited disorders.
• Adequate cell collection is vital for successful engraftment and treatment efficacy.

Purpose of the Study:

• To assess the feasibility and safety of bone marrow harvest for HSPC collection in pediatric patients undergoing gene therapy.
• To determine the optimal bone marrow volume and evaluate CD34+ cell yield for successful gene therapy in children with inherited disorders.

Main Methods:

• Fifty-seven pediatric patients (0.5-11.4 years) with ADA-SCID, WAS, or MLD underwent bone marrow harvest for HSPC-GT.
• Total nucleated cells and CD34+ cell counts were analyzed at various procedural stages.
• Correlation of CD34+ cell yield with patient weight and age was examined.

Main Results:

• A median bone marrow volume of 34.2 mL/kg was harvested, exceeding the minimum target volume.
• All patients achieved the minimum required CD34+ cell dose for infusion (median 10.3 × 10^6/kg).
• CD34+ cell yield showed an inverse correlation with patient weight and age, particularly in MLD patients.

Conclusions:

• Bone marrow harvest exceeding 30 mL/kg is well-tolerated in infants and children with ADA-SCID, WAS, and MLD.
• This procedure ensures adequate autologous HSPC collection for gene therapy, supporting successful treatment outcomes.