title: Early suppressive effects of chemotherapy and cytokine treatment on committed versus primitive haemopoietic progenitors in patient bone marrow.
abstract: These studies investigated the effectiveness of in vivo administration of cytokines in ameliorating potential marrow damage induced by chemotherapy. Breast cancer patients received 5-fluorouracil, leucovorin, doxorubicin and cyclophosphamide (FLAC) followed by either GM-CSF, PIXY321, or no cytokine. Marrow was obtained before and after one or two cycles of FLAC once blood cell counts had recovered. Colony-forming units for granulocytes and macrophages (CFU-GM) were used to indicate the effect of therapy on recovery of committed progenitor cells responsible for early blood cell recovery. The frequency and number of CFU-GM in marrow obtained after FLAC + PIXY321 were significantly lower than in marrow obtained after FLAC+GM-CSF or FLAC without cytokine. CD34+ cell numbers were also reduced after FLAC + PIXY321. CFU-GM production in marrow long-term cultures (LTC) was used to assess the effect of therapy on primitive progenitors. After 5 weeks the number of CFU-GM in LTC of post-therapy marrow from all three treatment arms was < 15% of the number in pre-therapy LTC. Suppressive effects of FLAC on primitive progenitors were observed even when committed progenitors and CD34+ cells had recovered to pre-therapy levels. These results demonstrate that cytokine treatment did not ameliorate suppressive or toxic effects of FLAC on the functional integrity of the marrow.
authors.affiliation: Medicine Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: G N
authors.initials: GN
authors.lastname: Schwartz
authors.forename: F
authors.initials: F
authors.lastname: Hakim
authors.forename: J
authors.initials: J
authors.lastname: Zujewski
authors.forename: J M
authors.initials: JM
authors.lastname: Szabo
authors.forename: R
authors.initials: R
authors.lastname: Cepada
authors.forename: D
authors.initials: D
authors.lastname: Riseberg
authors.forename: M K
authors.initials: MK
authors.lastname: Warren
authors.forename: C L
authors.initials: CL
authors.lastname: Mackall
authors.forename: A
authors.initials: A
authors.lastname: Setzer
authors.forename: M
authors.initials: M
authors.lastname: Noone
authors.forename: K H
authors.initials: KH
authors.lastname: Cowan
authors.forename: J
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: R E
authors.initials: RE
authors.lastname: Gress
mesh_terms: D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D015331:Cohort Studies; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000009:adverse effects; D004317:Doxorubicin / Q000009:adverse effects; D005472:Fluorouracil / Q000009:adverse effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D002955:Leucovorin / Q000009:adverse effects; D008264:Macrophages / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D018952:Antigens, CD34; D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D002955:Leucovorin; D005472:Fluorouracil