Erythropoietin Deficiency: A Complication of Cisplatin Therapy and Its Treatment with Recombinant Human Erythropoietin

Cisplatin (CDDP) has been implicated in the development of anemia via several mechanisms of action, including shortening of red cell (RBC) survival and direct toxicity of the drug on RBC bone marrow precursors. Recent studies and case reports suggest an association between CDDP and the development of hyporegenerative anemia as a consequence of relative erythropoietin (EPO) deficiency. To study the effects of CDDP on the relationship between serum EPO and hemoglobin (Hb) concentration, we measured levels of EPO in 12 patients (1-21 years of age) who were treated with cumulative doses of CDDP ranging from 300 to 720 mg/m2 for a variety of pediatric malignancies. Post-CDDP glomerular filtration rates (GFR) varied from 29 to 143 ml/min/1.73 m2 for 11 of the 12 patients studied. At the completion of CDDP therapy, an inverse linear relationship between log(10) serum EPO and Hb was noted among those patients who retained at least 40-50% of their pre-CDDP therapy GFR. One patient with chronic renal failure at the completion of CDDP therapy (GFR 25-35 ml/min/1.73 m2) exhibited a chronic transfusion-dependent, hyporegenerative anemia that was due to persistently low levels of EPO. Institution of recombinant human (r-Hu) EPO therapy resulted in an abrupt cessation of this patient's RBC transfusion dependency. Additional studies are needed to further characterize the effects of CDDP on EPO production and secretion and to determine optimal dosing schedules for r-Hu EPO in pediatric patients who receive CDDP and other myelosuppressive chemotherapy.