Early suppressive effects of chemotherapy and cytokine treatment on committed versus primitive haemopoietic progenitors in patient bone marrow

G. N. Schwartz, F. Hakim, J. Zujewski, J. M. Szabo, R. Cepada, D. Riseberg, M. K. Warren, C. L. Mackall, A. Setzer, M. Noone, K. H. Cowan, J. O'shaughnessy, R. E. Gress

Research output: Contribution to journalArticle

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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 CPU-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.

Original languageEnglish (US)
Pages (from-to)537-547
Number of pages11
JournalBritish Journal of Haematology
Volume92
Issue number3
DOIs
StatePublished - Jan 1 1996

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Leucovorin
Fluorouracil
Doxorubicin
Cyclophosphamide
Bone Marrow
Cytokines
Drug Therapy
Granulocyte-Macrophage Progenitor Cells
Therapeutics
Granulocyte-Macrophage Colony-Stimulating Factor
Stem Cells
Blood Cell Count
Poisons
Blood Cells
Cell Count
Breast Neoplasms

Keywords

  • Bone marrow long-term cultures
  • CD34 cells
  • Colony-forming units for granulocytes and macrophages
  • GM-CSF
  • PIXY321

ASJC Scopus subject areas

  • Hematology

Cite this

Early suppressive effects of chemotherapy and cytokine treatment on committed versus primitive haemopoietic progenitors in patient bone marrow. / Schwartz, G. N.; Hakim, F.; Zujewski, J.; Szabo, J. M.; Cepada, R.; Riseberg, D.; Warren, M. K.; Mackall, C. L.; Setzer, A.; Noone, M.; Cowan, K. H.; O'shaughnessy, J.; Gress, R. E.

In: British Journal of Haematology, Vol. 92, No. 3, 01.01.1996, p. 537-547.

Research output: Contribution to journalArticle

Schwartz, GN, Hakim, F, Zujewski, J, Szabo, JM, Cepada, R, Riseberg, D, Warren, MK, Mackall, CL, Setzer, A, Noone, M, Cowan, KH, O'shaughnessy, J & Gress, RE 1996, 'Early suppressive effects of chemotherapy and cytokine treatment on committed versus primitive haemopoietic progenitors in patient bone marrow', British Journal of Haematology, vol. 92, no. 3, pp. 537-547. https://doi.org/10.1046/j.1365-2141.1996.00387.x
Schwartz, G. N. ; Hakim, F. ; Zujewski, J. ; Szabo, J. M. ; Cepada, R. ; Riseberg, D. ; Warren, M. K. ; Mackall, C. L. ; Setzer, A. ; Noone, M. ; Cowan, K. H. ; O'shaughnessy, J. ; Gress, R. E. / Early suppressive effects of chemotherapy and cytokine treatment on committed versus primitive haemopoietic progenitors in patient bone marrow. In: British Journal of Haematology. 1996 ; Vol. 92, No. 3. pp. 537-547.
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AU - Cepada, R.

AU - Riseberg, D.

AU - Warren, M. K.

AU - Mackall, C. L.

AU - Setzer, A.

AU - Noone, M.

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