Treatment of Anemia in Myelodysplastic Syndromes With Granulocyte Colony-Stimulating Factor Plus Erythropoietin: Results From a Randomized Phase II Study and Long-Term Follow-Up of 71 Patients

Abstract

Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic syndromes (MDS) in approximately 20% of patients. Previous studies have suggested that treatment with the combination of granulocyte colony-stimulating factor (G-CSF) and epo may increase this response rate. In the present phase II study, patients with MDS and anemia were randomized to treatment with G-CSF + epo according to one of two alternatives; arm A starting with G-CSF for 4 weeks followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27 refractory anemia with excess blasts [RAEB]) were included in the study, three were evaluable only for epo as monotherapy and 47 for the combined treatment. The overall response rate to G-CSF + epo was 38%, which is identical to that in our previous study. The response rates for patients with RA, RARS, and RAEB were 20%, 46%, and 37%, respectively. Response rates were identical in the two treatment groups indicating that an initial treatment with G-CSF was not neccessary for a response to the combination. Nine patients in arm B showed a response to the combined treatment, but only three of these responded to epo alone. This suggests a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71 evaluable patients from both the present and the preceding Scandinavian study on G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic transformation during a median follow-up of 43 months was 28%. Twenty patients entered long-term maintenance treatment and showed a median duration of response of 24 months.The international prognostic scoring system (IPSS) was effective to predict survival, leukemic transformation, and to a lesser extent, duration of response, but had no impact on primary response rates.

Erythropoietin treatment of the anaemia of myelofibrosis with myeloid metaplasia: results in 20 patients and review of the literature

“…Multivariate analysis identified serum EPO <125 U/l as the only pretreatment variable associated with a favourable response to rHuEPO. This cut-off was similar to that previously reported by Rodríguez et al (1998), but lower than the serum EPO level (200 U/l) reported as the optimal cut-off for rHuEPO treatment of the anaemia of the myelodysplastic syndromes (Hellström-Lindberg et al, 1998). In addition, lack of transfusion support at the start of treatment was of borderline prognostic significance.…”

Treatment of anaemia in myelodysplastic syndromes with prolonged administration of recombinant human granulocyte colony‐stimulating factor and erythropoietin

“…Hence, despite some difficulties in comparing the results of our study with those of Hellstroem-Lindberg et al (1998) and Negrin et al (1996), our data lend further support to the concept of a growth factor combination treatment for anaemia in MDS patients.…”

“…Using the same response criteria of Negrin et al (1996), we obtained erythroid response rates of 61% (95% CI 41±78) after 12 weeks of cytokine treatment and of 80% (95% CI 59±93) after 36 weeks. If we apply the somewhat stricter criteria of Hellstroem-Lindberg et al (1998) to our data, we find a response rate of 50% (95% CI 31±69) after 12 weeks and 56% (95% CI 35±75) after 36 weeks.…”

“…Our study confirms the reports by other authors that a combination therapy with rhG-CSF and rhEPO is an effective treatment of anaemia associated with myelodysplastic syndromes. Although Negrin et al (1996) achieved a response rate of 48%, Hellstroem-Lindberg et al (1998) observed similar erythroid responses (38%) with slightly stricter response criteria.…”

“…Our treatment schedule differed from that used by Negrin et al (1996) and Hellstroem-Lindberg et al (1998) in an important aspect. We decided to proceed with the combination treatment for a much longer treatment interval than in any of the other studies.…”