Treatment of Anemia in Myelodysplastic Syndrome (MDS) with Darbepoetin-Alpha (DPO) and Granulocyte Colony Stimulating Factor (G-CSF).

Abstract

MDS is a clonal stem cell disorder characterized by ineffective hematopoiesis and peripheral cytopenias. Anemia is often severe, transfusion dependent and associated with impaired quality of life. Evidence shows that treatment with erythropoietin (EPO) has an overall response rate of 20% and with G-CSF becomes more effective with an erythroid response rate of around 40%. Studies have independently demonstrated a synergistic effect between EPO and G-CSF on the anemia of MDS. DPO, a modified form of EPO with a longer half life has been shown to be effective in correcting anemia in a significant proportion of MDS patients. Synergy between DPO and G-CSF has not been studied. We report the clinical course and changes in the blood counts in a 77 year old male diagnosed with MDS, Refractory Anemia with Excess Blasts Type I (RAEB-I) who received DPO and G-CSF combination treatment. His baseline CBC showed WBC-2.4 ×103/μL, Hb-9.7g/dL, and Plt-106×103/μL. EPO level was 64.4 mU/mL. He was initiated on EPO 20,000 units weekly (QW) which was titrated to 40,000 units QW after one month. His Hb increased to 12 g/dl. For convenience, he was switched from QW EPO injections to DPO 100 μg every two weeks (QOW). This was followed by an initial drop in the Hb to 11g/dL requiring an increase in DPO dose to 200 μg QOW which was followed by stabilization and maintenance of Hb between 10–11 g/dL. After 7 months, Hb dropped to 9 g/dL requiring an increase in DPO to 300 μg QOW. Hb increased to 10 g/dl and remained between 10–10.5 g/dL for 7 months. Hb dropped again to 8.3g/dL. The DPO dose was increased to 300 μg QW, and he was given a course of IV iron for a total of 1 gm. Following transient Hb increase to 9–10g/dL, for few months Hb dropped to 8g/dL and he became transfusion dependent. In addition, he became progressively neutropenic with ANC <500/μL and thrombocytopenic with Plt <50×103/μL. At this point he was initiated on G-CSF 480 μg TIW along with DPO 300 μg QW. One month after the initiation of DPO plus G-CSF his CBC showed WBC 4.0×103/μL, Hb-11.2 g/dL and Plt-92×103/μL. The Plt response was transient and eventually remained stable between 50–60 ×103/μL. He continues to remain transfusion independent after 8 months of combination treatment maintaining Hb between 10–11 g/dL. In addition to having a major erythrocyte and neutrophil response following the initiation of combination treatment of DPO and G-CSF, this patient also had transient Plt response. The course of this patient suggests that the addition of G-CSF to DPO may improve anemia and neutropenia in patients with MDS who do not have a sustained response to DPO alone. In addition it also suggests that in-vivo synergy may exist between DPO and G-CSF for the production of red cells in MDS.