MEGAKARYOCYTOPOIESIS AND GRANULOPOIESIS FOLLOWING CYCLOPHOSPHAMIDE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 100  (5) , 682-694
Abstract
CTX [cyclophosphamide; an antineoplastic drug] is a marrow-suppressant drug that has been reported to have a sparing effect on blood platelets. To investigate whether CTX spares platelet precursor cells and platelets, blood platelets, megakaryocytes and CFU-M [megakaryocyte progenitor cells] were studied in mice after the injection of CTX. The soft gel in vitro culture system was utilized to assay for CFU-M in marrow and spleen. CTX produced only a mild thrombocytopenia to 88-95% of control values. This was followed by a modest but significant thrombocytosis of 120% of controls on day 10. Despite the slight effect on blood platelets, striking changes were observed in megakaryocytes and CFU-M. Megakaryocytes and CFU-M were decreased to 10-25% of control values within 24 h of CTX administration. This was followed by a recovery of spleen megakaryocytes and CFU-M to normal within 6 days, followed by a 24-fold increase above control values in spleen megakaryocytes and a 29-fold increase in spleen CFU-M. In contrast, recovery of megakaryocytes and CFU-M in the marrow was delayed for 2 wk. An increase in marrow CFU-M above control values was not observed, although megakaryocytes increased to 150% of control. Granulocytes and their progenitor cells (CFU-GM [granulocyte-macrophage progenitor cells]) responded in a similar manner after CTX administration. Blood platelet levels are apparently only slightly decreased after a single injection of CTX; CFU-M and megakaryocytes are markedly decreased. The recovery and increased production of megakaryocytes and CFU-M in the face of a near-normal platelet level suggests that factors other than the platelet level are responsible for production of CFU-M and megakaryocytes.

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