Auto-SCT induces a phenotypic shift from CMP to GMP progenitors, reduces clonogenic potential and enhances in vitro and in vivo cycling activity defined by 18 F-FLT PET scanning

Abstract

Autologous SCT (auto-SCT) introduces a reduced tolerance to chemotherapy even in patients with adequate engraftment, suggesting long-term effects of the transplantation procedure on the BM capacity. To study the hematopoietic cell compartment after auto-SCT, CD34+ BM cells (n=16) from patients at 6-9 months after auto-SCT were studied with regard to the progenitor subsets, colony frequency and cell cycle status. The BM compartments were studied in vivo using PET tracer 3-fluoro-3-deoxy-L-thymidine (18 F-FLT PET). BM CD34+ cells after auto-SCT were compared with normal CD34+ cells and showed a phenotypic shift from common myeloid progenitor (CMP mean percentage 3.7 vs 19.4%, P=0.001) to granulocyte-macrophage progenitor (GMP mean percentage 51.8 vs 27.6%, P=0.01). In addition, a reduced clonogenic potential and higher cycling activity especially of the GMP fraction (41%±4 in G2/S phase vs 19%±2, P=0.03) were observed in BM after auto-SCT compared with normal. The enhanced cycling activity was confirmed in vivo by showing a significantly higher uptake of the 18 F-FLT PET tracer by the BM compartment. This study shows that auto-SCT results in defects of the hematopoietic compartment at least 6 months after auto-SCT, characterized by changes in the composition of progenitor subsets and enhanced in vitro and in vivo cycling activity. © 2011 Macmillan Publishers Limited All rights reserved.