Lithium Attenuation of Chemotherapy-Induced Granulocytopenia: Statistical and Clinical Significance?

  • F. Anthony Greco
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 127)


Does lithium significantly attenuate the degree and/or duration of chemotherapy-induced granulocytopenia? Several studies have addressed this question (Tisman, 1974; Greco, et al., 1976; Greco and Brereton, 1977; Stein et al., 1977; Catane et al., 1977; Lyman et al., 1978), and all have reported that the mean granulocyte nadir is significantly higher, or the mean or median duration of granulocytopenia is significantly shorter, following chemotherapy plus lithium (P values ranging between 0.01 and 0.05). There is not a single “negative” study reported. When these data are considered with the fact that lithium increases granulocyte production (Rothstein et al., 1978), one can easily conclude that the statistically significant attenuation of chemotherapy-induced granulocytopenia by lithium is a real effect. Further clarification of this significant effect requires detailed inspection of these data. It was obvious during our initial studies of lithium in patients receiving chemotherapy (Greco et al., 1976; Greco and Brereton, 1977) that the ability of lithium to limit the nadir of granulocytopenia was at best marginal except in a few patients. We were also uncertain, as were Stein and co-workers (Stein et al., 1977) if our “statistically significant” observations were biologically important. Therefore, I have again looked at the study of Stein and co-workers and carefully reviewed our own data (Greco and Brereton, 1977) in an attempt to gain a better appreciation of the observed “lithium effect.” At this writing, these two studies are the only detailed reports available. Both these studies report significant (P ≤ 0.05) lithium attenuation of granulocytopenia induced by chemotherapy.


Chemotherapy Cycle Bronchogenic Carcinoma Granulocyte Count Detailed Inspection Preliminary Clinical Trial 


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  1. Beyer, W.H., 1968, Non-Parametric Statistics, in: “Handbook of Tables for Probability and Statistics,” 2nd edition, p. 399, Chemical Rubber Company, Cleveland.Google Scholar
  2. Catane, R., Kaufman, J., Mittleman, A., Murphy, G.P., 1977, Attenuation myelosuppression with lithium, N. Eng. J. Med. 297:452.CrossRefGoogle Scholar
  3. Greco, F.A., Brereton, H.D., Pomeroy, T., 1976, Lithium carbonate attenuation of neutropenia, Pro. Amer. Soc, of Clin. Oncol. 17:250.Google Scholar
  4. Greco, F.A., Brereton, H.D., 1977, Effect of lithium carbonate on the neutropenia caused by chemotherapy: A preliminary clinical trial, Oncology 34: 153.PubMedCrossRefGoogle Scholar
  5. Lyman, G.H., Williams, C.C., Preston, D., 1978, A prospective randomized study of the effect of lithium carbonate on the granulocytopenia and incidence of infection associated with intensive chemotherapy and radiation therapy for undifferentiated small cell bronchogenic carcinoma. Blood 52:228, (Supplement 1).Google Scholar
  6. Rothstein, G., Clarkson, D., Larsen, W., Grosser, B.I., Athens, J.W., 1978, Effect of lithium on neutrophil mass and production, N. Eng. J. Med. 298:178.CrossRefGoogle Scholar
  7. Stein, R.S., Beaman, C., Ali, M.Y., Hansen, R., Jenkins, D.D., Jume’an, H.G., 1977, Lithium carbonate attenuation of chemotherapy-induced neutropenia, N. Eng. J. Med. 297:430.CrossRefGoogle Scholar
  8. Tisman, G., 1978, Lithium carbonate protection against drug-induced leukopenia in lymphosarcoma patients, IRCS 2:1509.Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • F. Anthony Greco
    • 1
  1. 1.Division of Oncology, Department of MedicineVanderbilt University Medical CenterNashvilleUSA

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