Human multilineage progenitor cell sensitivity to 4-hydroperoxycyclophosphamide

This institution has documented consistent reconstitution of hematopoiesis in patients treated with marrow lethal chemoradiotherapy who are "rescued" by reinfusion of autologous cryopreserved marrow cells incubated with 4-hydroperoxycyclophosphamide (4-HC) for in vitro purging of occult tumor cells. After 4-HC incubation, the reinfusion marrow cells showed marked reduction in committed progenitor cell (BFU-E, CFU-GM) frequency, and often total absence of detectable progenitors, without significant loss of marrow reconstituting ability. Since BFU-E and CFU-GM assays did not predict marrow reconstituting ability after 4-HC incubation, we sought to determine whether multilineage progenitor cells (CFU-GEMM) might be more resistant to 4-HC incubation and therefore a more reliable predictive assay in this setting. We found that BFU-E, CFU-GM, and CFU-GEMM all show similar dose-related sensitivity to in vitro incubation with 4-HC and do not appear representative of the cell(s) responsible for marrow reconstitution.