CYCLOPHOSPHAMIDE, DOXORUBICIN, VINCRISTINE, PREDNISONE DOSE INTENSIFICATION WITH GRANULOCYTE-COLONY-STIMULATING FACTOR MARKEDLY DEPLETES STEM-CELL RESERVE FOR AUTOLOGOUS BONE-MARROW TRANSPLANTATION

Hematopoietic growth factors allow dose escalation of chemotherapy. Th is approach may potentially reduce the quality and quantity of hematop oietic stem cells. The capacity of stem cells recovered after dose int ensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hem atopoietic engraftment was compared in two sequential trials of induct ion therapy (standard dose cyclophosphamide, doxorubicin, vincristine. prednisone [CHOP] without growth factors or dose intensification CHOP supported by granulocyte colony-stimulating factor [G-CSF]) followed by identical myeloablative therapy and autologous stem cell support. N eutrophil, platelet, and red blood cell (RBC) engraftment were compare d on days 100, 180, and 360 after stem cell reinfusion. Despite simila r patient characteristics including reinfusion of comparable numbers o f marrow mononuclear cells, after stem cell transplantation. a highly significant prolongation of neutrophil and platelet engraftment was se en in patients who received high dose CHOP and G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemo therapy and G-CSF recruited stem cells into a proliferative phase and that G-CSF allowed retreatment at a time when stem cells were suscepti ble to damage by cytotoxic therapy. Such inadequate hematologic engraf tment after myeloablative therapy might be avoided by either shortenin g the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additi onal stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be us ed with caution if stem cells are to be used to support myeloablative therapy. (C) 1997 by The American Society of Hematology.