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. 1981 May;67(5):1392–1399. doi: 10.1172/JCI110167

Cyclophosphamide treatment expands the circulating hematopoietic stem cell pool in dogs.

R A Abrams, K McCormack, C Bowles, A B Deisseroth
PMCID: PMC370705  PMID: 7229032

Abstract

Increased numbers of circulating granulocyte-monocyte precursor cells (CFUc) have been observed in the peripheral blood of man after antineoplastic chemotherapy. We have developed a canine model to study the biologic significance of this phenomenon for hematopoietic reconstitution following hematopoietically lethal exposure to total body irradiation (TBI). After cyclophosphamide administration, a 16-fold expansion of circulating CFUc numbers was observed during the period of rapid leukocyte recovery that occurred after the chemotherapy-induced leukocyte nadir. We had previously noted this association between leukocyte recovery and CFUc expansion in our human studies. After 900 rad TBI hematopoietic reconstitution was attempted with autologous, cryopreserved collections of peripheral blood mononuclear cells obtained either at times of post-cyclophosphamide CFUc expansion (group A, 14 dogs) or without CFUc expansion (group B, 12 dogs). Asd compared to group B collections, group A collections contained 11-fold more CFUc and were 12.5-fold more potent in fostering hematopoietic recovery after TBI. These results suggest that the expansion of CFUc numbers we observed was accompanied by a similar expansion of more primitive hematopoietic stem cell numbers. We conclude that chemotherapy-induced expansion of circulating CFUc numbers appears to be of substantial import in effecting hematopoietic reconstitution--an observation that may be of significance for further studies of autologous hematopoietic reconstitution in man.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrams R. A., Glaubiger D., Appelbaum F. R., Deisseroth A. B. Result of attempted hematopoietic reconstitution using isologous, peripheral blood mononuclear cells: a case report. Blood. 1980 Sep;56(3):516–520. [PubMed] [Google Scholar]
  2. Abrams R. A., Glaubiger D., Simon R., Lichter A., Deisseroth A. B. Haemopoietic recovery in Ewing's sarcoma after intensive combination therapy and autologous marrow infusion. Lancet. 1980 Aug 23;2(8191):385–389. doi: 10.1016/s0140-6736(80)90439-0. [DOI] [PubMed] [Google Scholar]
  3. Abrams R. A., Johnston-Early A., Kramer C., Minna J. D., Cohen M. H., Deisseroth A. B. Amplification of circulating granulocyte-monocyte stem cell numbers following chemotherapy in patients with extensive small cell carcinoma of the lung. Cancer Res. 1981 Jan;41(1):35–41. [PubMed] [Google Scholar]
  4. Appelbaum F. R., Herzig G. P., Graw R. G., Bull M. I., Bowles C., Gorin N. C., Deisseroth A. B. Study of cell dose and storage time on engraftment of cryopreserved autologous bone marrow in a canine model. Transplantation. 1978 Oct;26(4):245–248. doi: 10.1097/00007890-197810000-00008. [DOI] [PubMed] [Google Scholar]
  5. Barr R. D., Whang-Peng J., Perry S. Hemopoietic stem cells in human peripheral blood. Science. 1975 Oct 17;190(4211):284–285. doi: 10.1126/science.1179209. [DOI] [PubMed] [Google Scholar]
  6. Burgess A. W., Wilson E. M., Metcalf D. Stimulation by human placental conditioned medium of hemopoietic colony formation by human marrow cells. Blood. 1977 Apr;49(4):573–583. [PubMed] [Google Scholar]
  7. Debelak-Fehir K. M., Catchatourian R., Epstein R. B. Hemopoietic colony forming units in fresh and cryopreserved peripheral blood cells of canines and man. Exp Hematol. 1975 Apr;3(2):109–116. [PubMed] [Google Scholar]
  8. Deisseroth A., Abrams R. A. The role of autologous stem cell reconstitution in intensive therapy for resistant neoplasms. Cancer Treat Rep. 1979 Mar;63(3):461–471. [PubMed] [Google Scholar]
  9. GOODMAN J. W., HODGSON G. S. Evidence for stem cells in the peripheral blood of mice. Blood. 1962 Jun;19:702–714. [PubMed] [Google Scholar]
  10. Goldman J. M. Modern approaches to the management of chronic granulocytic leukemia. Semin Hematol. 1978 Oct;15(4):420–430. [PubMed] [Google Scholar]
  11. Gorin N. C., Herzig G., Bull M. I., Graw R. G., Jr Long-term preservation of bone marrow and stem cell pool in dogs. Blood. 1978 Feb;51(2):257–265. [PubMed] [Google Scholar]
  12. Hershko C., Gale R. P., Ho W. G., Cline M. J. Cure of aplastic anaemia in paroxysmal nocturnal haemoglobinuria by marrow transfusion from identical twin: Failure of peripheral-leucocyte transfusion to correct marrow aplasia. Lancet. 1979 May 5;1(8123):945–947. doi: 10.1016/s0140-6736(79)91720-3. [DOI] [PubMed] [Google Scholar]
  13. Kovàcs P., Bruch C., Fliedner T. M. Colony formation by canine hemopoietic cells in vitro. Inhibition by polymorphonuclear leukocytes. Acta Haematol. 1976;56(2):107–115. doi: 10.1159/000207926. [DOI] [PubMed] [Google Scholar]
  14. McCredie K. B., Hersh E. M., Freireich E. J. Cells capable of colony formation in the peripheral blood of man. Science. 1971 Jan 22;171(3968):293–294. doi: 10.1126/science.171.3968.293. [DOI] [PubMed] [Google Scholar]
  15. Nothdurft W., Bruch C., Fliedner T. M., Rüber E. Studies on the regeneration of the CFU-C population in blood and bone marrow of lethally irradiated dogs after autologous transfusion of cryopreserved mononuclear blood cells. Scand J Haematol. 1977 Nov;19(5):470–481. doi: 10.1111/j.1600-0609.1977.tb01503.x. [DOI] [PubMed] [Google Scholar]
  16. Pike B. L., Robinson W. A. Human bone marrow colony growth in agar-gel. J Cell Physiol. 1970 Aug;76(1):77–84. doi: 10.1002/jcp.1040760111. [DOI] [PubMed] [Google Scholar]
  17. Quesenberry P., Levitt L. Hematopoietic stem cells (second of three parts). N Engl J Med. 1979 Oct 11;301(15):819–823. doi: 10.1056/NEJM197910113011505. [DOI] [PubMed] [Google Scholar]
  18. Rich K. C., Richman C. M., Mejias E., Daddona P. Immunoreconstitution by peripheral blood leukocytes in adenosine deaminase-deficient severe combined immunodeficiency. J Clin Invest. 1980 Aug;66(2):389–395. doi: 10.1172/JCI109868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Richman C. M., Weiner R. S., Yankee R. A. Increase in circulating stem cells following chemotherapy in man. Blood. 1976 Jun;47(6):1031–1039. [PubMed] [Google Scholar]
  20. Sarpel S. C., Zander A. R., Harvath L., Epstein R. B. The collection, preservation and function of peripheral blood hematopoietic cells in dogs. Exp Hematol. 1979 Feb;7(2):113–120. [PubMed] [Google Scholar]
  21. Spitzer G., Verma D. S., Fisher R., Zander A., Vellekoop L., Litam J., McCredie K. B., Dicke K. A. The myeloid progenitor cell--its value in predicting hematopoietic recovery after autologous bone marrow transplantation. Blood. 1980 Feb;55(2):317–323. [PubMed] [Google Scholar]
  22. Storb R., Graham T. C., Epstein R. B., Sale G. E., Thomas E. D. Demonstration of hemopoietic stem cells in the peripheral blood of baboons by cross circulation. Blood. 1977 Sep;50(3):537–542. [PubMed] [Google Scholar]

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