Megakaryocytopoiesis and granulopoiesis following cyclophosphamide

CTX 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 as well as platelets, blood platelets, megakaryocytes, and CFU-M 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% to 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% to 25% of control values within 24 hr 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 weeks. 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) responded in a similar manner after CTX administration. These results indicate that blood platelet levels are only slightly decreased after a single injection of CTX whereas 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.