title: Cyclophosphamide, doxorubicin, vincristine, prednisone dose intensification with granulocyte colony-stimulating factor markedly depletes stem cell reserve for autologous bone marrow transplantation.
abstract: Hematopoietic growth factors allow dose escalation of chemotherapy. This approach may potentially reduce the quality and quantity of hematopoietic stem cells. The capacity of stem cells recovered after dose intensification to support myeloablative therapy is unknown. In patients with previously untreated advanced follicular lymphoma, trilineage hematopoietic engraftment was compared in two sequential trials of induction 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. Neutrophil, platelet, and red blood cell (RBC) engraftment were compared on days 100, 180, and 360 after stem cell reinfusion. Despite similar patient characteristics including reinfusion of comparable numbers of marrow mononuclear cells, after stem cell transplantation, a highly significant prolongation of neutrophil and platelet engraftment was seen in patients who received high dose CHOP and G-CSF in comparison to standard dose CHOP. These findings suggest that dose intensified chemotherapy and G-CSF recruited stem cells into a proliferative phase and that G-CSF allowed retreatment at a time when stem cells were susceptible to damage by cytotoxic therapy. Such inadequate hematologic engraftment after myeloablative therapy might be avoided by either shortening the time that growth factor support is administered, lengthening the interval between cycles, or attempting to repetitively harvest additional stem cells either from the marrow or peripheral blood. Therefore, intensification of chemotherapy with growth factor support must be used with caution if stem cells are to be used to support myeloablative therapy.
authors.affiliation: Division of Hematologic Malignancies and Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Freedman
authors.forename: D
authors.initials: D
authors.lastname: Neuberg
authors.forename: P
authors.initials: P
authors.lastname: Mauch
authors.forename: J
authors.initials: J
authors.lastname: Gribben
authors.forename: R
authors.initials: R
authors.lastname: Soiffer
authors.forename: K
authors.initials: K
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Robertson
authors.forename: D C
authors.initials: DC
authors.lastname: Fisher
authors.forename: R
authors.initials: R
authors.lastname: Schlossman
authors.forename: M
authors.initials: M
authors.lastname: Kroon
authors.forename: C
authors.initials: C
authors.lastname: Rhuda
authors.forename: C
authors.initials: C
authors.lastname: Kuhlman
authors.forename: J
authors.initials: J
authors.lastname: Ritz
authors.forename: L
authors.initials: L
authors.lastname: Nadler
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008224:Lymphoma, Follicular / Q000097:blood / Q000628:therapy*; D008297:Male; D011241:Prednisone / Q000008:administration & dosage; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone