1. Bone marrow harvesting from paediatric patients undergoing haematopoietic stem cell gene therapy
- Author
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Maddalena Migliavacca, Paola Massariello, Roberto Miniero, Laura Lorioli, Laura Castagnaro, Francesca Tucci, Francesca Fumagalli, Francesco Calzatini, Miriam Casiraghi, Luca Santoleri, Claudia Fossati, Daniele Canarutto, Marcella Facchini, Maria Pia Cicalese, Fabio Ciceri, Alessandra Biffi, Matilde Zambelli, Sarah Marktel, Valeria Calbi, Stefano Zancan, Marta Claudia Frittoli, Paolo Silvani, Gigliola Antonioli, Giulia Consiglieri, Raffaella Milani, Silvia Darin, Francesca Ferrua, Salvatore Recupero, Maria Ester Bernardo, Salvatore Gattillo, Rossana Fiori, Alessandro Aiuti, Federica Barzaghi, Michele Manfredini, Tucci, F., Frittoli, M., Barzaghi, F., Calbi, V., Migliavacca, M., Ferrua, F., Fumagalli, F., Lorioli, L., Castagnaro, L., Facchini, M., Fossati, C., Zancan, S., Massariello, P., Manfredini, M., Consiglieri, G., Canarutto, D., Recupero, S., Calzatini, F., Casiraghi, M., Darin, S., Antonioli, G., Miniero, R., Fiori, R., Silvani, P., Zambelli, M., Marktel, S., Gattillo, S., Milani, R., Santoleri, L., Ciceri, F., Biffi, A., Cicalese, M. P., Bernardo, M. E., and Aiuti, A.
- Subjects
Male ,medicine.medical_specialty ,Transplantation Conditioning ,Genetic enhancement ,Urology ,CD34 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Bone Marrow ,Medicine ,Humans ,Progenitor cell ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Genetic Therapy ,medicine.disease ,Metachromatic leukodystrophy ,Haematopoiesis ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Bone marrow ,Stem cell ,business ,Ex vivo ,030215 immunology - Abstract
Collection of an adequate amount of autologous haematopoietic stem progenitor cells (HSPC) is required for ex vivo manipulation and successful engraftment for certain inherited disorders. Fifty-seven paediatric patients (age 0.5–11.4 years) underwent a bone marrow harvest for the purpose of HSPC gene therapy (GT), including adenosine deaminase-severe combined immunodeficiency (ADA-SCID), Wiskott–Aldrich syndrome (WAS) and metachromatic leukodystrophy (MLD) patients. Total nucleated cells and the percentage and absolute counts of CD34+ cells were calculated at defined steps of the procedure (harvest, CD34+ cell purification, transduction with the gene transfer vector and infusion of the medicinal product). A minimum CD34+ cell dose for infusion was 2 × 106/kg, with an optimal target at 5–10 × 106/kg. Median volume of bone marrow harvested was 34.2 ml/kg (range 14.2–56.6). The number of CD34+ cells collected correlated inversely with weight and age in all patients and particularly in the MLD children group. All patients reached the minimum target dose for infusion: median dose of CD34+ cells/kg infused was 10.3 × 106/kg (3.7–25.9), with no difference among the three groups. Bone marrow harvest of volumes > 30 ml/kg in infants and children with ADA-SCID, WAS and MLD is well tolerated and allows obtaining an adequate dose of a medicinal product for HSPC-GT.
- Published
- 2019