Erythropoetin (EPO) and Granulocyte Colony Stimulating Factor (GCS-F) Based Therapy in Patients with Low Risk MDS: A Single Centre Experience from India.

MDS is a group of clonal disorders characterized by ineffective erythropoiesis and peripheral cytopenias. We report our single centre experience of treatment of low risk MDS. A total of 68 patients (M:F 49:19) were treated with either EPO or EPO with G-CSF combination and followed up for a period of 6 years. MDS diagnosis was based on the WHO criteria and patients with MDS-RAEB were excluded. The mean age was 48 years(range:24–72yrs). This treatment was offered as an upfront therapy in view of non feasibility of other modalities of treatment(e.g., non- availability of HLA matched donors, poor clinical status and co-morbid conditions). Patients were randomly divided into 2 Arms. Arm ‘A’ (n = 55) received EPO(10,000 units) once a week and G-CSF(150μg) alternate day for 12 weeks. 13 Patients in Arm ‘B’ received EPO alone in same dose for 12 weeks. If a patient did not show an erythroid response in Arm ‘B’, he / she was shifted to the combination arm. Once adequate erythroid response was achieved, patients were put on lowest effective EPO dose. Patients who interrupted their treatment in between for whatever reasons were excluded (n =10) from study.14 Patients who showed a decline in response were given an escalated dose of EPO (20,000 units per week).

The overall erythroid response rate was 58%. It was partial (100% reduction in red cell transfusion requirement) in 30% of patients and complete (maintaining hemoglobin at >11.5 G/dL without red cell transfusion) in 28%. The median response duration was 28 months (range:6–72 months). Erythroid response was better in the first Arm (65%) vis-à-vis Arm B (33%). Patients, who started therapy before they became transfusion dependent, achieved an earlier response within 8 weeks(range:4–24 weeks). The complete responders also showed a longer duration of response than the partial responders.35% of patients progressed to AML after a median duration of 28 months(range:3–60 months). Eleven patients who stopped therapy (5:AML progression, 6:unrelated causes) were excluded from the analysis. Patients with IPSS Low group showed durable response than the patients with Int-1 group. Though there was no definite survival benefit, the responders became transfusion free or less dependent on transfusion without any adverse effect on the outcome, thereby improving the quality of life.

The erythroid response in our patients was better than in most reported series in the west. However, the progression to AML was 35% in our patients during the 60 months follow-up duration, which is marginally higher than the western series and it is important to be further studied. In conclusion, patients with IPSS low / Int-1 score should be offered EPO+ G-CSF combination therapy to achieve a durable response in contrast to the patients with high risk IPSS patients, in developing countries.