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. 1973 Dec;52(12):3220–3230. doi: 10.1172/JCI107522

Periodic Hematopoiesis in Human Cyclic Neutropenia

D Guerry IV 1,2, D C Dale 1,2, M Omine 1,2, S Perry 1,2, S M Wolff 1,2
PMCID: PMC302598  PMID: 4750451

Abstract

Human cyclic neutropenia is characterized by severe depression of blood neutrophil levels approximately every 21 days. To investigate the mechanism of cyclic neutropenia four patients were studied with daily complete blood counts, serial bone marrow examinations, marrow reserve testing, serum muramidase determinations, DF22P granulocytokinetic studies, and, in one patient, in vivo [3H]TdR labeling. Periodogram analysis of the serial blood counts in the latter patient and visual inspection of multiple cycles in the others revealed periodic fluctuations in the levels of blood neutrophils, monocytes, lymphocytes, reticulocytes, and platelets. Rhythmic changes in the morphologic and radioisotopic studies as well as the marrow reserve tests and muramidase measurements were consonant with a mechanism of periodic failure of marrow production rather than peripheral destruction. Human cyclic neutropenia is analogous to cyclic neutropenia in the grey collie dog and may be viewed as the consequence of cyclic hematopoiesis.

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Selected References

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

  1. ATHENS J. W., HAAB O. P., RAAB S. O., BOGGS D. R., ASHENBRUCKER H., CARTWRIGHT G. E., WINTROBE M. M. LEUKOKINETIC STUDIES. XI. BLOOD GRANULOCYTE KINETICS IN POLYCYTHEMIA VERA, INFECTION, AND MYELOFIBROSIS. J Clin Invest. 1965 May;44:778–788. doi: 10.1172/JCI105190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. ATHENS J. W., HAAB O. P., RAAB S. O., MAUER A. M., ASHENBRUCKER H., CARTWRIGHT G. E., WINTROBE M. M. Leukokinetic studies. IV. The total blood, circulating and marginal granulocyte pools and the granulocyte turnover rate in normal subjects. J Clin Invest. 1961 Jun;40:989–995. doi: 10.1172/JCI104338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. ATHENS J. W., MAUER A. M., ASHENBRUCKER H., CARTWRIGHT G. E., WINTROBE M. M. Leukokinetic studies. I. A method for labeling leukocytes with diisopropyl-fluorophosphate (DFP32). Blood. 1959 Apr;14(4):303–333. [PubMed] [Google Scholar]
  4. BOGGS D. R., ATHENS J. W., CARTWRIGHT G. E., WINTROBE M. M. LEUKOKINETIC STUDIES. IX. EXPERIMENTAL EVALUATION OF A MODEL OF GRANULOPOIESIS. J Clin Invest. 1965 Apr;44:643–656. doi: 10.1172/JCI105177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BRECHER G., SCHNEIDERMAN M., WILLIAMS G. Z. Evaluation of electronic red blood cell counter. Am J Clin Pathol. 1956 Dec;26(12):1439–1449. doi: 10.1093/ajcp/26.12.1439. [DOI] [PubMed] [Google Scholar]
  6. Bradley T. R., Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966 Jun;44(3):287–299. doi: 10.1038/icb.1966.28. [DOI] [PubMed] [Google Scholar]
  7. Bull B. S., Schneiderman M. A., Brecher G. Platelet counts with the Coulter counter. Am J Clin Pathol. 1965 Dec;44(6):678–688. doi: 10.1093/ajcp/44.6.678. [DOI] [PubMed] [Google Scholar]
  8. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  9. CARTWRIGHT G. E., ATHENS J. W., WINTROBE M. M. THE KINETICS OF GRANULOPOIESIS IN NORMAL MAN. Blood. 1964 Dec;24:780–803. [PubMed] [Google Scholar]
  10. COUTEL Y., MOREL H., THOMET G. [Cyclic neutropenia in a 6-year-old child]. Nouv Rev Fr Hematol. 1963 Jul-Aug;3:482–490. [PubMed] [Google Scholar]
  11. CRONKITE E. P., FLIEDNER T. M. GRANULOCYTOPOIESIS. N Engl J Med. 1964 Jun 25;270:1403–CONCL. doi: 10.1056/NEJM196406252702608. [DOI] [PubMed] [Google Scholar]
  12. Cream J. J. Prednisolone-induced granulocytosis. Br J Haematol. 1968 Sep;15(3):259–267. doi: 10.1111/j.1365-2141.1968.tb01537.x. [DOI] [PubMed] [Google Scholar]
  13. Dale D. C., Alling D. W., Wolff S. M. Application of time series analysis to serial blood neutrophil counts in normal individuals and patients receiving cyclophosphamide. Br J Haematol. 1973 Jan;24(1):57–644. doi: 10.1111/j.1365-2141.1973.tb05727.x. [DOI] [PubMed] [Google Scholar]
  14. Dale D. C., Alling D. W., Wolff S. M. Cyclic hematopoiesis: the mechanism of cyclic neutropenia in grey collie dogs. J Clin Invest. 1972 Aug;51(8):2197–2204. doi: 10.1172/JCI107027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dale D. C., Brown C. H., Carbone P., Wolff S. M. Cyclic urinary leukopoietic activity in gray collie dogs. Science. 1971 Jul 9;173(3992):152–153. doi: 10.1126/science.173.3992.152. [DOI] [PubMed] [Google Scholar]
  16. Dale D. C., Ward S. B., Kimball H. R., Wolff S. M. Studies of neutrophil production and turnover in grey collie dogs with cyclic neutropenia. J Clin Invest. 1972 Aug;51(8):2190–2196. doi: 10.1172/JCI107026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dale D. C., Wolff S. M. Studies of the neutropenia of acute malaria. Blood. 1973 Feb;41(2):197–206. [PubMed] [Google Scholar]
  18. Deinard A. S., Page A. R. An improved method for performing neutrophil survival studies. Blood. 1970 Jul;36(1):98–110. [PubMed] [Google Scholar]
  19. Fink M. E., Finch S. C. Serum muramidase and granulocyte turnover. Proc Soc Exp Biol Med. 1968 Feb;127(2):365–367. doi: 10.3181/00379727-127-32692. [DOI] [PubMed] [Google Scholar]
  20. Geelhoed G. W., Kane M. A., Dale D. C., Wells S. A. Colon ulceration and perforation in cyclic neutropenia. J Pediatr Surg. 1973 Jun;8(3):379–382. doi: 10.1016/0022-3468(73)90105-x. [DOI] [PubMed] [Google Scholar]
  21. Kimball H. R., Vogel J. M., Perry S., Wolff S. M. Quantitative aspects of pyrogenic and hematologic responses to etiocholanolone in man. J Lab Clin Med. 1967 Mar;69(3):415–427. [PubMed] [Google Scholar]
  22. LITWACK G. Photometric determination of lysozyme activity. Proc Soc Exp Biol Med. 1955 Jul;89(3):401–403. doi: 10.3181/00379727-89-21824. [DOI] [PubMed] [Google Scholar]
  23. Lund J. E., Padgett G. A., Ott R. L. Cyclic neutropenia in grey collie dogs. Blood. 1967 Apr;29(4):452–461. [PubMed] [Google Scholar]
  24. MECHANIC R. C., FREI E., 3rd, LANDY M., SMITH W. W. Quantitative studies of human leukocytic and febrile response to single and repeated doses of purified bacterial endotoxin. J Clin Invest. 1962 Jan;41:162–172. doi: 10.1172/JCI104459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Maloney M. A., Patt H. M. Granulocyte transit from bone marrow to blood. Blood. 1968 Feb;31(2):195–201. [PubMed] [Google Scholar]
  26. Morley A. Periodic diseases, physiological rhythms and feedback control--a hypothesis. Australas Ann Med. 1970 Aug;19(3):244–249. doi: 10.1111/imj.1970.19.3.244. [DOI] [PubMed] [Google Scholar]
  27. PAGE A. R., GOOD R. A. Studies on cyclic neutropenia; a clinical and experimental investigation. AMA J Dis Child. 1957 Dec;94(6):623–661. doi: 10.1001/archpedi.1957.04030070035006. [DOI] [PubMed] [Google Scholar]
  28. Perry S., Moxley J. H., 3rd, Weiss G. H., Zelen M. Studies of leukocyte kinetics by liquid scintillation counting in normal individuals and in patients with chronic myelocytic leukemia. J Clin Invest. 1966 Sep;45(9):1388–1399. doi: 10.1172/JCI105447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. RICHAR W. J., BREAKELL E. S. Evaluation of an electronic particle counter for the counting of white blood cells. Am J Clin Pathol. 1959 May;31(5):384–393. doi: 10.1093/ajcp/31.5.384. [DOI] [PubMed] [Google Scholar]
  30. Senn J. S., McCulloch E. A., Till J. E. Comparison of colony-forming ability of normal and leukaemic human marrow in cell culture. Lancet. 1967 Sep 16;2(7516):597–598. doi: 10.1016/s0140-6736(67)90742-8. [DOI] [PubMed] [Google Scholar]
  31. VIDEBAEK A. Cyclic neutropenia: report on three cases. Acta Med Scand. 1962 Dec;172:715–721. doi: 10.1111/j.0954-6820.1962.tb07213.x. [DOI] [PubMed] [Google Scholar]

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