Cisplatin-associated anemia: an erythropoietin deficiency syndrome.

Abstract

Cisplatin-based therapy results in a cumulative anemia that is disproportionate to the effects on other blood cells. The severity of this treatment-induced anemia and the resultant transfusion requirement in cancer patients correlate with cisplatin-induced renal tubular dysfunction. Observed/expected serum erythropoietin (EPO) ratios decline with progressive cisplatin therapy and are proportionate to the degree of renal dysfunction. Recovery from anemia and of observed/expected serum EPO ratios in patients occurs after cessation of cisplatin therapy, along with restoration of renal tubular function. Creatinine clearance, however, remains permanently depressed. Cisplatin-treated rats develop progressive renal dysfunction and anemia that persists for many weeks, without effects on white blood cell counts. The anemia is also associated with a lack of expected EPO and reticulocyte response. With EPO administration, cisplatin-treated rats exhibit a greater reticulocyte response and hematocrit increment then non-cisplatin-treated rats given EPO, indicating minimal erythroid precursor cell damage from cisplatin. These results indicate the primary etiology of cisplatin-associated anemia is a transient, but persisting EPO deficiency state resulting from cisplatin-induced renal tubular damage, which can be prevented or treated by hormone (EPO) replacement. (J. Clin. Invest. 1995. 95:1650-1659

Kinetics of haematopoietic recovery after dose‐intensive chemo/radiotherapy in mice: optimized erythroid support with darbepoetin alpha

“…The onset and degree of reticulocyte recovery and subsequent Hb recovery was incrementally delayed across the cycles of treatment. The model, therefore, appeared to reflect the acute impact of CRT, accumulated marrow damage across multiple cycles and a possible blunting of endogenous erythropoietin production (Wood et al, 1995). This pattern was also seen with the white blood cell (WBC) counts and platelet counts.…”

Platinum drugs in the treatment of non-small-cell lung cancer

“…Anemia can also occur during treatment with cisplatin. This can be due to several mechanisms, including depletion of intrinsic erythropoietin production (caused by peritubular renal cell depletion), reduced bone marrow stem cell activity and the absence of the stem cell reaction of administered erythropoietin (Dufour et al, 1990;Canpolat et al, 1994;Wood and Hrushesky, 1995).…”

The effects of iron deficiency on estradiol-induced suppression of erythropoietin induction in rats: implications of pregnancy-related anemia

“…1 Renal Epo production is up-regulated by anemia, hypoxia, transition metals such as cobalt (Co) or nickel, and iron chelators. 2 Plasma Epo levels, reflecting the amount of renal production, are useful in clinical diagnosis of renal diseaserelated anemia, including renal tubular dysfunction [3][4][5] as well as chronic renal failure, 6,7 in which plasma Epo levels are not elevated in response to the anemia. Chronic diseases without renal injury, such as malignancy or inflammation, can also produce anemia due to the functional suppression of Epo induction in the kidney.…”