Peripheral Blood Is The Stem Cell Source Of Choice For Reduced Intensity Stem Cell Transplant In Children

Biology of Blood and Marrow Transplantation(2010)

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摘要
Reduced intensity conditioning (RIC) enables SCT in children with pre-existing organ toxicity. However, there are concerns about mixed chimerism(MC) in the long term that is sometimes not sufficient for cure. In a cohort of 148 patients undergoing RIC SCT (Fludarabine 150 mg/m2, Melphalan 140 mg/m2, Campath 1H 0.6-1 mg/kg) we compared chimerism between those who received BM (n=109) Vs PBSC (n=41). Median age at transplant was 3.6 years and median follow-up was 4.7 years.The majority were transplanted for primary immunodeficiency disorders (n=120) and donors were MUD (n=67), mMUD (n=45), MSD (n=17), MFD (n=14) and mMFD (n=8). Survival was equivalent, 70% for BM and 75% for PBSC. Incidence of aGVHD≥ grade 2 was higher with PBSC (40% vs 20% for BM) but the incidence of chronic GVHD was low (10%). Chimerism studies were done using STR at 1, 3, 6, 9 and 12 months post transplant and 3 monthly thereafter. All but one child engrafted but 4 children had early autologous reconstitution. At 1 year post SCT 65%, 9%, 9% and 7% had complete donor chimerism (CC), high MC (50-95% donor chimerism), low MC (10-49% donor chimerism) and very low MC (<10% donor chimerism) respectively and these were stable at last follow-up. All children with CC and high MC are cured of their disease. 26 children (17%) had low or very low MC. The incidence of low and very low MC was significantly higher with BM (24/109,22%) than with PBSC (2/41,5%).Children with low and very low level MC had a poorer prognosis: 5/26 needed a second transplant, 3/26 died, 2 had DLI, 1 CD34 top-up, 1 has ongoing poor immune reconstitution. In conclusion, use of PBSC leads to good long term chimerism with acceptable GVHD and we advocate that PBSC should be the stem cell source of choice in RIC SCT in children.
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stem cell
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