Skip to main content
. Author manuscript; available in PMC: 2014 Aug 7.
Published in final edited form as: Blood Rev. 2013 Jul 27;27(5):243–259. doi: 10.1016/j.blre.2013.07.003

Table 2.

The impact of erythropoiesis-stimulating agents (ESAs) on overall survival in patients with MDS. Listed below are the 3 large positive retrospective analyses and the negative, but underpowered, prospective randomized study that evaluated impact of ESAs on survival in patients with MDS.

Study Number of patients (median age) Patient characteristics and protocol Results Survival
Golshayan AR et al. (Reference [45])
Pooled analysis		 Pooled analysis of 162 studies with 2592 patients (68 year for growth factor [GF] group
Vs.
66 year for non-growth factor (NGF) group)

  • Pathologically-confirmed RA, RARS, <5% BM blasts

    GF: erythropoietin (EPO), G-CSF, GM-CSF, interleukins

    vs.

    NGF group

  • ORR: GF group 39.5% Vs. NGF group 31.4% (P = 0.019 in multivariate analysis)

  • Erythroid responses: GF group 66.8% vs. NGF group 61.4%

  • CR/PR: GF group 9.1% vs. NGF group 25% (P = 0.03)

  • Median response duration: GF group 18 m vs. NGF group: 13 m (P = 0.38)

  • After adjustment for baseline characteristics, the 24-month OS rate in the GF group was 78.5% Compared to 67.8% in the NGF group (P = 0.005)
Park S et al. (Reference [44])
A French Retrospective analysis		 403 (median age 74 years)

  • IPSS: Low (n = 139), INT-1 (n = 164), INT-2 (n = 37), high (n = 6), undetermined (n = 57)

  • FAB: RA (n = 143), RARS (n = 142), RAEB (n = 118)

  • Hb <10 g/dl—100%, > 2 U RBC need in the past 2 months 36%, Serum EPO < 500 mU/mL (93%)

    EPO α or β

    60 000 U SC weekly or darbepoetin

    300 μg with or without filgrastim or lenograstim

  • Erythroid responses (50% by IWG 2006 criteria with median duration 24 months, and 62% by IWG 2000 criteria [40% major, 22% minor] with media duration of 20 months).

  • Predictors of higher response rates: < 10% BM blasts, IPSS low and INT-1, RBC transfusion-independence, serum EPO level < 200 mU/mL only with IWG 2006 criteria, shorter interval between diagnosis and treatment

  • Predictors of longer response duration: major response (IWG 2000 criteria), IPSS low and INT-1, BM blasts <5%, and absence of multilineage dysplasia.

  • Multilineage dysplasia was not associated with lower response rates

  • No difference in response rates between patients treated with rEPO alone or with G-CSF

  • 5-year OS was better in the EPO-treated group compared to untreated MDS cohort (64% vs. 39%, P = 0.001), but OS benefit was restricted to EPO-responders.

  • In multivariate analysis, EPO therapy was independently associated with better OS (HR = 0.43, 95%CI, 0.25–0.72).

  • There was no increased 5-year incidence of leukemic progression with EPO therapy (12.2% in EPO-treated vs. 13.3% in EPO-untreated patients, P = 0.21).
Jadersten M et al. (Reference [46])
A Nordic Retrospective analysis		 121 EPO + G-CSF-treated patients (71 years)
Compared to 237 untreated matched patients (66 years)

  • FAB: RA, RARS, RAEB

  • Hb <10 g/dL or regular transfusion need

    EPO + G-CSF

  • EPO + G-CSF: Erythroid response rate 39%, transfusion independence 29%

  • Median response duration 23 months (range, 3 to 116+ months).

 Multivariate analysis: EPO-G-CSF was associated with better OS (HR 0.61. 95%CI 0.44–0.83; P = 0.002) and decreased risk of non-leukemic death (HR 0.66, 95%CI 0.44–0.99; P = 0.042)

  • The OS benefit was primarily in patients with lower transfusion needs (< 2 RBC Units/month, HR 0.44, 95%CI 0.29–.66; P < 0.001)

  • EPO + G-CSF not associated with leukemic progression even in patients with excess blasts or poor cytogenetics
Greenberg PL et al. (Reference [42])
Prospective randomized phase 3 study (designed to provide an 80% power to detect 46% reduction in HR in the ESA group)		 EPO (n = 53)
vs.
Supportive care (SC) (n = 57)
Median age 73 years

  • FAB: RA, RARS, RAEB-1, Nonproliferative CMML

  • Hb < 9.5 g/dL, 61% with transfusion dependence

    EPO 150–300 U/Kg daily ± G-CSF (1 μg/kg/day) and SC vs. SC alone

 At 4 m: Erythroid response rate (ESA: 36%, SC 9.6%) and transfusion dependence (EPO 29%, SC 51%).
Response to ESA associated with serum EPO level (45% vs. 5% in patients with serum EPO <200 vs. ≥ 200 mU/mL, respectively).

  • Median follow-up of 5.8 years: no significant differences in OS between the EPO vs. SC-treated groups (median, 3.1 vs. 2.6 years) or in leukemic progression (7.5% vs. 10.5% respectively)

  • Erythroid responders had significantly longer OS compared to non-responders (median, 5.5 vs. 2.3 years, P = 0.004)

GF: Growth factor; NGF: Non-growth factor; EPO: Erythropoietin; G-CSF: Granulocyte colony-stimulating factor; GM-CSF: Granulocyte-macrophage colony-stimulating factor; rEPO: Recombinant human erythropoietin; ORR: Overall response rate; CR: Complete remission; PR: Partial remission; PFS: Progression-free survival; IPSS: International Prognostic Scoring System; INT-1: Intermediate-1; INT-2: Intermediate 2; RA: Refractory anemia; RARS: Refractory anemia with ring sideroblasts; RAEB: Refractory anemia with excess blasts; RBC: Red blood cells; Hb: Hemoglobin; SC: Supportive care; CMML: Chronic myelomonocytic leukemia; IWG: International Working Group criteria.