Anemia is frequent at diagnosis and during the treatment of aggressive lymphoma. In the previous LNH 98-5 study, 72 % of the patients had, at the diagnosis, a hemoglobin level inferior to 13 g/dl. Moreover, during the treatment, 92 % of the patients had a hemoglobin level less than 13 g/dl and 30 % were transfused. The presence of anemia at diagnosis is an indicator of poor prognosis in multivariate analysis. This prognosis impact could probably be explained at cellular level on the tumor. Tumoral hypoxia is increased by the presence of anemia. Due to this hypoxia, the expression of tumor growth factor may be increased: e.a VEGF and the induction of expression of multi drug resistance (MDR1) is observed. This resistance to treatment is also due to the inhibition of genotoxic activity of free radicals induced by ionised radiation and chemotherapy. Experimentally, the negative impact of hypoxia on the efficacy of chemotherapy has been demonstrated in sarcoma cell lines for doxorubicin, vincristine and all most cyclophosphamide. Finally, hypoxia induced over expression of apoptosis resistance genes and induced a growth advantage for apoptosis resistant tumoral lines. Improvement of survival in patients receiving erythropoetin with chemotherapy or radiotherapy was suggested in a study on patients treated with a neoadjuvant radiochemotherapy for head and neck cancer. Erythropoetin could act to protect several normal tissues during chemotherapy and thus could decrease treatment related morbidity. Darbepoetin alfa is a new recombinant protein stimulating erythropoiesis. Thus, the use of darbepoetin alfa, in association with chemotherapy, could increase CR rate, EFS and OS in patients treated for diffuse large B-cell lymphoma.