Patient and Methods: This was a prospective randomized, single-center, open-label, 12-week case-control study of epoetin alfa in pediatric patients with acute lymphoblastic leukemia (ALL) in remission receiving maintenance chemotherapy. Sixty patients were randomly assigned to receive either epoetin alfa (rHuEPO group = 30 cases, 17 males & 13 female), or no epoetin alfa (control group = 30 cases, 16 males & 14 females). Both groups were matched as regard age, sex, baseline Hb concentration, remission state, chemotherapy regimen, numbers and amount of blood transfusion, and leukemia state (both were low and standard risk). The median age was 7 years (range 3 11 y). Epoetin alfa was administered at a dose of 450 IU/kg, once weekly, subcutaneously (sc) for 12 consecutive weeks. Endpoints were changes in hematologic and quality of life (QOL) parameters. Results: Among the 30 patients evaluable for hematologic response, the mean increase in Hb from baseline to time of final evaluation was 2.0ยฑ1.2 g/dl (p < 0.05). An increase in Hb of 2 g/dl, in the absence of blood transfusion, occurred in 70% of patients (21 of 30 patients) who were on the study for 30 days. The overall response rate (Hb increase 2 g/dl or Hb 12 g/dl in the absence of blood transfusion) was 80% (24 of 30 patients). In 30 patients who were evaluable for QOL assessment, epoetin-a therapy was found to significantly (p < 0.05) improve mean Cancer Linear Analog Scale (CLAS) scores for energy level, ability to perform daily activity, and overall QOL from baseline to the time of final evaluation. QW epoetin-a was found to be well tolerated. Conclusion: Treatment with QW epoetin-a was found to increase Hb levels, decrease transfusion requirement, and improve functional status and QOL in anemic patients with ALL in maintenance receiving chemotherapy. The once-weekly schedule is convenient, safe, and may reduce the burden on patients, parents, and their caregivers by reducing the number of visits to the clinic.