Originally published as JCO Early Release 10.1200/JCO.2007.15.4906 on June 16 2008

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Erythropoietin and Granulocyte-Colony Stimulating Factor Treatment Associated With Improved Survival in Myelodysplastic Syndrome

Martin Jädersten, Luca Malcovati, Ingunn Dybedal, Matteo Giovanni Della Porta, Rosangela Invernizzi, Scott M. Montgomery, Cristiana Pascutto, Anna Porwit, Mario Cazzola, Eva Hellström-Lindberg

From the Karolinska Institutet, Department of Medicine, Division of Hematology, Clinical Epidemiology Unit, and Department of Pathology, Karolinska University Hospital, Stockholm, Sweden; Department of Hematology, and Department of Medicine, University of Pavia and Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; and the Department of Hematology, Rikshospitalet Hospital, Oslo, Norway

Corresponding author: Martin Jädersten, MD, Hematology Center M54, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden; e-mail: martin.jadersten{at}ki.se

Purpose To assess the effect of erythropoietin (EPO) plus granulocyte-colony stimulating factor (G-CSF) treatment on survival and leukemic transformation in myelodysplastic syndrome (MDS).

Patients and Methods We compared the long-term outcome of patients with MDS treated with EPO plus G-CSF (n = 121) with untreated patients (n = 237) with MDS using multivariate Cox regression with delayed entry, for the first time adjusting for all major prognostic variables (WHO classification, karyotype, cytopenias, level of transfusion-need, age, and sex).

Results The erythroid response rate to EPO plus G-CSF was 39%, and the median response duration 23 months (range, 3 to 116+). In the multivariate analysis, treatment was associated with improved overall survival (hazard ratio, 0.61; 95% CI, 0.44 to 0.83; P = .002). Interestingly, this positive association was primarily observed in patients requiring fewer than 2 units of RBCs per month. Treatment was not linked to the rate of acute myeloid leukemia in any defined subgroup, including patients with an increase of marrow blasts or an unfavorable karyotype.

Conclusion The inherent risk of leukemic evolution in MDS makes the current investigation highly relevant, in light of the recent reports of potential negative effects of EPO treatment on outcome in patients with cancer. We conclude that treatment of anemia in MDS with EPO plus G-CSF may have a positive impact on outcome in patients with no or low transfusion need, while not affecting the risk of leukemic transformation.

published online ahead of print at www.jco.org on June 16, 2008.

Supported by grants from Associazione Italiana per la Ricerca sul Cancro, Milan; Fondazione Cariplo, Milan; Fondazione Ferrata Storti, Pavia; and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy (M.C.), Cancer Society in Stockholm (A.P.), and Swedish Cancer Society 3689-B06-12XCC, 4912-B07-04PDF, Cancer Society Stockholm 051143 (E.H.-L.).

M.J. and L.M. contributed equally to this article.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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