Erythropoietin plus granulocyte colony-stimulating factor is better than erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes: results from a randomized single-centre study

Abstract

Haemopoietic growth factors (HGF), i.e. erythropoietin [recombinant human erythropoietin (rHEPO)] or granulocyte colony stimulating factor (G-CSF), alone or in combination, have largely been used to treat anemia in myelodysplastic syndromes (MDS), but whether combined rHEPO and G-CSF is really superior to rHEPO alone is still under debate. In particular, randomized studies comparing front-line rHEPO vs rHEPO+G-CSF are still lacking. The aim of this study was to compare the effects of "standard" doses of rHEPO with the combination of rHEPO and G-CSF in the treatment of anemic patients with low-risk MDS in a prospective randomized trial. Anemic patients with low-risk MDS were randomly assigned to receive either rHEPO (10,000 IU s.c. three times a week) or the same dosage of rHEPO+G-CSF (300 mug s.c. twice a week) for a minimum of 8 weeks. Patients who were unresponsive to rHEPO were offered the combination therapy for another 8 weeks, whereas non-responders to rHEPO+G-CSF were considered "off study". Responders continued the treatment indefinitely. Both haematological response and changes in quality-of-life (QoL) scores (Functional Assessment of Cancer Therapy-Anemia) were recorded and evaluated. Thirty consecutive patients [10 refractory anemia (RA), 5 RA with ringed sideroblasts, 7 refractory cytopenia with multilineage dysplasia, 5 RA with less than 10% blasts and 3 5q-syndrome] were enrolled in the study. All of them (15 in the rHEPO arm and 15 in the rHEPO+G-CSF arm) were valuable after the first 8 weeks of treatment. Erythroid response was observed in 6/15 (40%) patients in the rHEPO arm and in 11/15 (73.3%) patients in the rHEPO+G-CSF arm. In 4/9 (44.4%) patients who were unresponsive to rHEPO, the addition of G-CSF induced erythroid response at 16 weeks. No relevant adverse effects were recorded for either treatment in any of the study patients. Erythroid response to HGF was associated with a relevant improvement in QoL. Twenty responders continued the treatment. Afterwards, 8/20 (40%) discontinued therapy because of the following: losing response (2), progression to high-risk MDS (3) and death due to other causes (3). The remaining 12 are still responding and continuing treatment, with a median follow-up of 28 months. Progression to acute leukemia was cumulatively observed in 4/30 (13.3%) patients (2 in each arm). Although our data were obtained from a relatively small cohort of patients, they indicate that the rHEPO+G-CSF treatment is more effective than rHEPO alone for correcting anemia in low-risk MDS patients and for making a relevant improvement in their QoL.

Is there a role for all-trans retinoic acid in combination with recombinant erythropoetin in myelodysplastic syndromes? A report on 59 cases

“…28 In patients resistant to an ESA alone, its combination with G-CSF or GM-CSF also yields 20-40% erythroid responses. 6,[29][30][31][32][33] However, ESA-G-CSF combinations give disappointing results in patients with high endogenous EPO levels, 7 similar to what we observed with the epoetin-b-ATRA combination.…”

Development and validation of QOL-E© instrument for the assessment of health-related quality of life in myelodysplastic syndromes

“…Several studies have reported a positive correlation between Hb levels and HRQoL [9,19,20,[24][25][26][27][28][29][30][31], although this correlation is not consistent [6]. The current data reinforce the notion of a relationship between Hb levels and QOL-E© as specific patient-reported outcome in MDS patients.…”

Clinicopathological Features of Nigerians With Myelodysplastic Syndromes

“…However, because of the cost, only 1 of our patients who could afford some doses of rhEpo had the growth factor, which was however not found to be effective. Studies have however shown that best results are obtained when rhEpo is combined with G-CSF (14). Although only one patient presented with marked leucopenia, and three with significant neutropenia (Tables 1 and 2), more than 50% of them presented with features of infection at presentation.…”