Effect of cis‐diamminedichloroplatinum on erythropoietin production and hematopoietic progenitor cells

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Abstract
Studies were conducted to determine whether the progressive development of anemia associated with the antineoplastic drug cis‐diamminedichloroplatinum (cDDP) was the consequence of decreased erythropoietin (Epo) production due to cDDP‐induced nephrotoxicity or selective inhibition of erythroid progenitor cells. Five days after a single intraperitoneal injection of cDDP, hypoxia‐induced Epo production was not decreased in mice and was increased significantly in rats in spite of severe multifocal tubular necrosis. In both species, colony‐forming units‐granulocyte macrophage (CFU‐gm) and colony‐forming units‐erythroid (CFU‐e) were reduced significantly, with a greater decrease in CFU‐e. Studies of an anemic patient receiving cDDP also showed elevated Epo and decreased CFU‐gm and CFU‐e. In vitro exposure of mouse and human bone marrow to cDDP casued a dose‐dependent inhibition of CFU‐gm and CFU‐e in both species, with human CFU‐e showing greatest sensitivity. The results indicate that the primary hematologic toxicity of cDDP is directed at the hematopoietic stem cell compartment.