Rationale: Myelodysplastic syndrome (MDS) is characterized by peripheral blood cytopenia, a major cause of morbidity and mortality. Two current treatments that may ameliorate cytopenia in MDS are azacitidine (aza) and hematopoietic growth factors. When used alone in MDS, erythropoietin (epo) and G-CSF are reported to increase the hemoglobin level and the neutrophil count, respectively. Additionally, epo and G-CSF may work synergistically to improve anemia and neutropenia. This study examined whether the combination of growth factors and aza would be more effective than aza alone for the treatment of MDS.

Methods: We identified 86 MDS patients treated at our institution who received an average of 10.8 cycles of aza. Forty-nine (49) of these patients also received either epo, G-CSF or both during the course of their aza treatment, while 37 did not receive hematopoietic growth factors. These 2 groups did not differ significantly either in number of cycles of aza received (p=0.34) or FAB MDS subtype (p=0.50). Hematological responses were tabulated by International Working Group criteria and compared using chi-square statistics.

Results: Patients treated with aza alone had a 51% (19/37) overall hematological response rate (OHR). Patients who received aza + epo (A + E) had a 50% (6/12) OHR and when compared to aza alone (A), was not statistically different (p=0.9). Patients who received aza + G-CSF +/− epo (A + G +/− E) had an 84% (31/37) OHR versus 51% (25/49) in patients who did not receive G-CSF (A +/− E) (p=0.003). When the group A + G +/− E was compared to A +/− E there was a statistically significant difference in favor of A + G +/− E in erythroid (77% vs. 37%; p=0.001) and platelet (72% vs. 47%; p=0.04) response, but no difference in neutrophil response (71% vs. 67%; p=0.9).

Conclusion: In patients with MDS treated with aza the addition of G-CSF improved OHR, erythroid and platelet response. Surprisingly, neutrophil response was not improved. The biological basis for these observations suggests an effect upon erythroid and megakaryocytic lineages. We postulate that G-CSF may have an anti-apoptotic effect as has been previously demonstrated when used in combination with epo.

Disclosures: Our Division of Hematology/Oncology has received research funding from Pharmion Corporation to complete an extensive review of a large group of patients treated with azacitidine at our institution.; James M. Rossetti and Richard K. Shadduck are on the Speakers Bureau of Pharmion Corporation and have received honoraria for speaking engagements.

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