An assessment of erythroid response to epoetin α as a single agent versus in combination with granulocyte– or granulocyte‐macrophage–colony‐stimulating factor in myelodysplastic syndromes using a meta‐analysis approach

Abstract

BACKGROUND: Epoetin α (EPO) continues to be the initial treatment of choice for most anemic patients with myelodysplastic syndromes (MDS). Over the years, different therapeutic strategies have been adopted to optimize the clinical benefits of EPO in this setting. METHODS: In the current meta‐analysis of published literature, erythroid response (ER) rates with EPO as a single agent versus its combination with granulocyte–colony‐stimulating factor (G‐CSF) or granulocyte‐macrophage–colony‐stimulating factor (GM‐CSF) were compared. RESULTS: The assessment indicated that the ER rates were comparable between the 2 EPO‐based therapeutic strategies. Furthermore, EPO monotherapy at a higher dose of 60,000 to 80,000 U weekly produced significantly higher ER rates (64.5%) compared with the standard oncology dose of 30,000 to 40,000 U weekly either as a single agent (49%; P < .001) or in combination with G‐CSF/GM‐CSF (50.6% P = .007). In addition, when transfusion‐dependent patients were assessed separately, both EPO monotherapy and its combination with G‐CSF/GM‐CSF produced comparable and appreciable levels of transfusion independence (28.8% and 24.8%, respectively). CONCLUSIONS: In the current meta‐analysis, higher doses of EPO demonstrated better ER rates compared with EPO at standard doses alone or in combination with G‐CSF/GM‐CSF. Furthermore, the authors concluded that prospective clinical studies are warranted to evaluate the use of higher doses of EPO in anemic patients with MDS. Cancer 2009. © 2009 American Cancer Society.

Distinct Signal Transduction Abnormalities and Erythropoietin Response in Bone Marrow Hematopoietic Cell Subpopulations of Myelodysplastic Syndrome Patients

“…This enhanced signaling could contribute to the progressive depletion of early hematopoietic cells seen in patients with MDS due to defective self-renewal, differentiation, and quiescence (22). ERK1/2 is only marginally activated in basal conditions in CD34 þ cells, and completely unphosphorylated in (28) and who therefore are predicted to have the highest probability of response to erythropoietin (plus G-CSF) treatment, as confirmed in a recent meta-analysis (29). Within this subset of possibly responsive patients, the cytofluorimetric test described here strongly predicted the clinically nonresponsive patients.…”

Current therapeutic approaches for patients with myelodysplastic syndromes

“…The addition of GCSF (lenigrastim) has improved the response rate to approximately 40%, particularly for patients with ring sideroblasts (Negrin et al, 1996;Hellstrom-Lindberg et al, 1997Casadevall et al, 2004). Although increased erythroid responses have been noted with the addition of GCSF to EPO as well as with increased EPO doses (Greenberg et al, 2009b), a meta-analysis of data using these regimens demonstrated higher responses with the drug combination mainly in patients with relatively lower dose EPO monotherapy (Mundle et al, 2009). Darbepoetin (a longer acting version of EPO) has demonstrated similar and perhaps improved efficacy at doses of 150-300 lg sc every 1-2 weeks (Musto et al, 2005;Stasi et al, 2005;Mannone et al, 2006;Gotlib et al, 2008).…”

Azacitidine for the treatment of lower risk myelodysplastic syndromes

“…For patients with MDS, the IPSS provides an estimated evaluation of life expectancy and transformation to AML that can vary from a few months to several years, according to the level of risk. 1 Among the current therapeutic options available for patients with lower risk MDS, it has been established that erythropoiesis-stimulating agents (ESAs), [6][7][8][9][10][11][12] immunomodulatory drugs like thalidomide and lenalidomide, [13][14][15][16][17][18][19] and immunosuppressive therapies 20,21 can at least partially restore hematopoiesis and induce transfusion independence in selected patients. However, with the possible exception of younger patients who are candidates for allogeneic stem cell transplantation, [21][22][23] transfusions and chelating therapy remain widely used treatment options for a large number patients.…”