Role of Erythropoietin in the Late Anemia of Patients with Chronic Myeloid Leukemia Treated Frontline with Imatinib

Background Late occurrence of moderate/severe anemia in patients with Chronic Myeloid Leukemia (CML) during long-lasting treatment with imatinib has been reported in a sizeable rate and seems to be more common in elderly patients. Treatment of such complication is subjective and the possible role of erythropoietin (EPO) still unclear.

Methods To highlight this issue, we revised retrospectively 37 CML patients treated at 10 Institutions in Italy with frontline imatinib for at least 24 months and in stable complete cytogenetic response (CCyR) who developed a late chronic anemia and were treated with EPO. Late chronic anemia was defined as the presence of persistent (> 3 months) and otherwise unexplained (creatinine level < 2 mg/dl, normal iron balance, bilirubin level < 2 mg/dl, folate and Vitamin B12 in the normal range) Hb levels < 11 g/dl which occurred > 6 months from imatinib start. The main clinical features of the patients at diagnosis were as follows: male/female 21/16 (56.8%/43.2%), median age 69.4 years [interquartile range (IQR) 62.7 - 74.8], median Hb 12.2 g/dl (IQR 10.9 - 13.5), median WBC 50.3 x 10⁹/l (IQR 28.7 - 87.2), median PLTS 384 x 10⁹/l (IQR 277 - 645). According to Sokal risk classification, available in 35 patients, 7 (20.0%) were low risk, 24 (68.6%) intermediate risk and 4 (11.4%) high risk.

Results Median time from imatinib start to EPO treatment was 44.2 months (IQR 21.6 - 100.2). At baseline of EPO treatment, all patients were in stable CCyR and 31/37 (83.7%) were also in stable MR 3.0. Median Hb value at baseline was 9.9 g/dl (IQR 9.2 - 10.2): four out 37 patients (10.8%) needed packed red cell transfusions before the starting of EPO treatment. Endogenous EPO level at baseline was available in 22 patients, with a median value of 21.5 mU/ml (IQR 13.6 - 35.7). Alpha-EPO (40,000 UI weekly) was employed in 31 cases, beta-EPO (30,000 UI weekly) in 4 cases and darbopoietin (150 mcg/weekly) in 2 patients. On the whole, 29 patients (78.3%) achieved an erythroid response, defined as a stable (> 3 months) increment > 1.5 g/dl of Hb levels, and 8 patients (21.7%) were resistant to treatment: median HB values at different time-points during EPO treatment are reported in the figure 1. Among responding patients, 3 had a relapse of anemia after 8, 24 and 96 months from EPO start, respectively, and stopped EPO, 4 died while in response from CML unrelated causes, 2 stopped EPO while in response: the remaining 20 responding patients are still alive in response and still in treatment with EPO. No EPO-related toxicity was observed. 5-year overall survival from EPO treatment of the entire cohort was 81.0% (95%CI 65.7 - 96.3).

Conclusions Results with EPO in the treatment of late chronic anemia which occurs during long-lasting imatinib treatment are encouraging, with a high rate of response and an excellent safety profile: however, larger prospective studies are warranted to define more precisely the role (when to start EPO?, at what dosage?, for how long?) of such an approach in the treatment of this common late complication of prolonged imatinib therapy.

View largeDownload slide

View largeDownload slide

Close modal