Serum erythropoietin levels in patients receiving intensive chemotherapy and radiotherapy

Abstract

To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient. The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits. Epo levels were measured by radioimmunoassay (RIA). For each patient, baseline serum Epo levels were determined at time of admission to the hospital. Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT. Hematocrits (Hcts) were measured daily. All patients had an initial serum creatinine less than or equal to 1.5 mg/dL. Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed. Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased. The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter. While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period. Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy. We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post- BMT. Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted.

The combination of erythropoietin and granulocyte colony‐stimulating factor increases the rate of haemopoietic recovery with clinical benefit after peripheral blood progenitor cell transplantation

“…We did not observe the same phenomenon in our patients following autologous PBPCT. However, this fact is in agreement with previous reports in which the administration of EPO alone or EPO plus GM-CSF after autologous marrow transplantation did not potentiate erythroid recovery (Pene et al, 1993;Locatelli et al, 1994) In this regard, several studies have shown that endogenous EPO production is frequently restricted in recipients of allogeneic marrow transplantation (Ireland et al, 1990;Schapira et al, 1990;Beguin et al, 1991), whereas we and others observed an appropriate EPO production after autologous transplantation or PBPCT (Ireland et al, 1990;Beguin et al, 1991;Bosi et al, 1991;Baiocchi et al, 1993). Hence, the lack of potentiation of the erythroid recovery by EPO plus G-CSF after PBPCT probably reflects the minor role of EPO in promoting erythropoiesis following autologous transplantation, as recently described by Beguin et al (1993), although a reduction of red blood cell transfusion in patients treated with EPO after allogeneic transplantation was observed by Link et al (1994).…”

Serum erythropoietin titers in hematological malignancies and related diseases

“…This may result from the partial disturbance of Epo production in the kidney caused by the administration of cytotoxic drugs in lymphoma and myeloma or kidney dysfunction in myeloma. Schapiru et al [6] also suggested that intensive chemotherapy might result in blunted endogenous Epo response irrespective of the anemia.…”

Plasma erythropoietin concentrations in patients receiving intensive platinum or nonplatinum chemotherapy

“…Renal function was not related to Epo production. The ®nding that cytostatic treatments caused an increase in Epo response not triggered by anaemia or hypoxia has been observed by several authors [6,8,10,11]. Various interpretations have been proposed for the observed serum Epo increase before the decrease in Hb after treatment with cytostatic drugs: (1) cytotoxic therapy causes direct injury to Epo production cells in the kidney in manner that mimics hypoxia; (2) bone marrow inhibition triggers an unknown stimulus for Epo production; recently some authors observed an inverse relationship between erythroid activity and Epo levels after myelosuppressive therapy [12]; (3) a decreased mass of erythroid precursors disrupts the usual Epo degradation pathway, reduced Epo use resulting in prolonged Epo lifespan and concentration [13]; (4) as protein synthesis and protein transcription are necessary for the normal degradation of Epo mRNA, it is also possible that cytotoxic drugs could enhance Epo mRNA stability with a consequent increase in protein synthesis.…”