TY - JOUR
T1 - Bone marrow harvesting from paediatric patients undergoing haematopoietic stem cell gene therapy
AU - Tucci, Francesca
AU - Frittoli, Marta
AU - Barzaghi, Federica
AU - Calbi, Valeria
AU - Migliavacca, Maddalena
AU - Ferrua, Francesca
AU - Fumagalli, Francesca
AU - Lorioli, Laura
AU - Castagnaro, Laura
AU - Facchini, Marcella
AU - Fossati, Claudia
AU - Zancan, Stefano
AU - Massariello, Paola
AU - Manfredini, Michele
AU - Consiglieri, Giulia
AU - Canarutto, Daniele
AU - Recupero, Salvatore
AU - Calzatini, Francesco
AU - Casiraghi, Miriam
AU - Darin, Silvia
AU - Antonioli, Gigliola
AU - Miniero, Roberto
AU - Fiori, Rossana
AU - Silvani, Paolo
AU - Zambelli, Matilde
AU - Marktel, Sarah
AU - Gattillo, Salvatore
AU - Milani, Raffaella
AU - Santoleri, Luca
AU - Ciceri, Fabio
AU - Biffi, Alessandra
AU - Cicalese, Maria Pia
AU - Bernardo, Maria Ester
AU - Aiuti, Alessandro
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41409-019-0573-6
DO - 10.1038/s41409-019-0573-6
M3 - Article
C2 - 31150018
AN - SCOPUS:85066493585
VL - 54
SP - 1995
EP - 2003
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 12
ER -