FACTORS AFFECTING THE MOBILIZATION OF PRIMITIVE AND COMMITTED HEMATOPOIETIC PROGENITORS INTO THE PERIPHERAL-BLOOD OF CANCER-PATIENTS

Rapid hematopoietic reconstitution following peripheral blood progenit or cell (PBPC) autotransplantation is thought to result from reinfusio n of committed progenitor cells, This has raised concern that PBPC aut ografts might be rich in committed hematopoietic progentors responsibl e for early engraftment, but deficient in more primitive progenitors r equired for long-term hematopoietic reconstitution, The granulomonocyt ic colony-forming unit (CFU-GM) assay measures committed progenitors r esponsive to a single species of colony-stimulating activity such as g ranulocyte-macrophage colony-stimulating factor (GM-CSF), whereas the pre-CFU assay identifies more primitive progenitors by measuring inter leukin-3 (IL-3) and kit ligand (ML) induced generation of secondary CF U-GM from CD34(+), 4-hydroperoxycyclophosphamide resistant progentiors that require multiple cytokine stimuli, Paired bone marrow (BM) and P BPC samples from 17 breast and ovarian cancer patients participating i n four separate clinical trials were compared in these assay systems, In seven of nine patients, PBPC autografts mobilized with cyclophospha mide rebound and G-CSF compared favorably with paired BM autografts in both committed and primitive progenitor capacity, Failure to mobilize substantial primitive progenitor cell numbers occurred in two of nine patients undergoing this mobilization regimen and could not have been predicted by either circulating CFU-GM or CD34(+) cell number, Prior myelosuppressive treatment experiences reduced peripheral progenitor y ields somewhat, but still allowed for the collection of PBPC autograft s which compared favorably with BM autografts in total CFU-GM and Pre- CFU, Mobilization of PBPC with G-CSF or GM-CSF alone in patients who h ad received prior myelosuppressive therapies produced autografts which were relatively deficient in committed progenitors, but absolutely de ficient in primitive progenitors, We conclude that optimization of pat ient characteristics and mobilization parameters can achieve PBPC auto grafts rich in both primitive and committed hematopoietic progenitor c ells.