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.
Bone marrow harvesting from paediatric patients undergoing haematopoietic stem cell gene therapy / 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.; Aiuti, A.. - In: BONE MARROW TRANSPLANTATION. - ISSN 0268-3369. - 54:12(2019), pp. 1995-2003. [10.1038/s41409-019-0573-6]
Bone marrow harvesting from paediatric patients undergoing haematopoietic stem cell gene therapy
Consiglieri G.;Canarutto D.;Recupero S.;Milani R.;Ciceri F.;Cicalese M. P.;Bernardo M. E.Penultimo
Data Curation
;Aiuti A.
2019-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
