The hallmark of Myelodysplastic Syndrome (MDS) is ineffective production of myeloid blood cells and a risk of transformation to acute myelogenous leukemia (AML). Anemia requiring blood transfusion is present in 90% of patients. Therapy with erythropoietin (EPO) alone or with granulocyte-colony stimulating factor (G-CSF) is currently the standard of care for anemia in low risk MDS. Recent reports have raised concerns over whether treatment with these hematopoietic growth factors negatively affects outcomes in cancer patients; increasing relapses and decreasing overall survival in several types of cancers. In contrast to these findings, a recent study by Park et al suggests a positive impact of growth factors on survival in MDS without affecting the rate of progression to AML, but the multivariate analysis used in the study did not adjust for all currently used prognostic factors.(1)

In this study, Jädersten and colleagues sought to confirm these findings with a cohort analysis using a multivariate regression that does adjust for all major prognostic variables; WHO classification, karyotype, cytopenias, level of transfusion need, age and sex. The EPO plus G-CSF treatment cohort (n = 121) included all patients from 3 Nordic trials. All patients had refractory anemia with ringed sideroblasts or excess blasts in combination with hemoglobin less than 10 g/dL or regular transfusion need. The control cohort (n= 237) was selected from an Italian cohort of untreated patients based on the same criteria as the EPO plus G-CSF group. Both cohorts were enrolled during the same time period (1990-1999) in Western Europe with detailed recording of prognostic factors. The EPO plus G-CSF patients were significantly older and more frequently transfused than untreated patients, which would imply a worse prognosis in this group than the untreated group.

EPO plus G-CSF treatment was associated with longer survival mainly in patients with low transfusion needs, defined as fewer than 2 units of red blood cells per month. This result correlates with the observation that patients in this subgroup had a better response to EPO plus G-CSF treatment than the more heavily transfused. No association with survival was seen in this more heavily transfused group. There was no association between treatment and the risk of AML progression in any group.

The authors conclude that treatment of anemia in MDS with EPO and G-CSF may have a positive impact on survival in patients with low or no transfusion need, while not affecting the risk of leukemic transformation. They opine that these findings are highly relevant in light of recent reports of potential negative effects of EPO treatment on outcome in cancer patients. Jädersten and colleagues feel that therapy with EPO and G-CSF should remain the standard of care for anemia in low risk MDS.

Jädersten M, Malcovati L, Dybedal I, Della Porta MG, Invernizzi R, Montgomery SM, Pascutto C, Porwit A, Cazzola M, Hellström-Lindberg E. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol. 2008 Jul 20;26(21):3607-13.

NAAC Expert Commentary:
This report offers some reassurance in these days of heightened anxiety regarding the use of growth factors and cancer progression. In this case, patients with MDS were treated with both G-CSF and EPO without apparent acceleration of disease or more frequent transformation to acute leukemia. The latter is of particular importance because although most MDS patients do not progress to overt leukemia, a fair percentage do. Even though there are hypothetical reasons that growth factors such as these may be considered risky interventions, this analysis supports what clinicians have observed: that EPO and G-CSF can be used safely in MDS patients.

The data on improved survival is interesting, but must be interpreted with caution. These were two distinct cohorts from two different European countries; one on clinical trial (G-CSF + EPO) and the other receiving ‘supportive care’ off protocol. Although the authors make every effort to match control (untreated patient) with their protocol-registered patients, definitive conclusions regarding survival benefit from treatment are best drawn from randomized, prospective studies. Clearly these randomized, prospective studies need to be conducted in order to determine if the survival advantage suggested by this retrospective cohort comparison could actually be confirmed in a controlled clinical trial setting.

References

1. Park S, Grabar S, Kelaidi C, Beyne-Rauzy O, Picard F, Bardet V, Coiteux V, Leroux G, Lepelley P, Daniel MT, Cheze S, Mahé B, Ferrant A, Ravoet C, Escoffre-Barbe M, Adès L, Vey N, Aljassem L, Stamatoullas A, Mannone L, Dombret H, Bourgeois K, Greenberg P, Fenaux P, Dreyfus F; GFM group (Groupe Francophone des Myélodysplasies). Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood. 2008 Jan 15;111(2):574-82.

Last Updated: November 7, 2008