Fludarabine, cytarabine, and granulocyte-colony stimulating factor for the treatment of high risk myelodysplastic syndromes

BACKGROUND. The prognosis of patients with high risk myelodysplastic syndromes (MDS) (i.e., refractory anemia with excess of blasts [RAEB] and refractory anemia with excess of blasts in transformation [RAEB-t]) usually is poor. The combination of fludarabine, cytarabine, and granulocyte-colony stimulating factor (G-CSF) (FLAG regimen) has been reported to be effective in patients with these diseases. METHODS, Forty-two patients (32 with RAEB-t and 10 with RAEB) were treated with the FLAG regimen. The median age was 61 years (range, 27-74 years). Forty patients were diagnosed with primary MDS and 2 patients had treatment-related MDS. Induction therapy was comprised of the FLAG regimen, whereas consolidation therapy included idarubicin and cytarabine. Patients with a compatible donor and who were age < 50 years were scheduled to undergo an allogeneic bone marrow transplantation (BMT), whereas for those patients without a donor and who were age < 60 years autologous BMT with peripheral blood stem cells mobilized by the consolidation regimen plus G-CSF was planned. RESULTS. Complete remission (CR) was achieved in 31 of 42 patients (74%; 95% confidence interval, 60-87%). Death during induction therapy occurred in 4 patients (9%) whereas 7 patients (17%) were resistant to the FLAG regimen. Toxicity from the consolidation regimen was negligible. All patients age < 50 years and achieving CR were eligible for allogeneic BMT procedures, with early recurrence being the only reason for exclusion. The median overall survival and disease free survival were 13 months and 18 months, respectively. Patients with favorable cytogenetics had a significantly better outcome compared with those patients with an adverse karyotype. CONCLUSIONS, The FLAG regimen is effective in patients with high risk MDS as well as in patients age > 60 years. The toxicity of the regimen is low and the majority of patients are eligible to undergo allogeneic BMT procedures after induction/consolidation therapy. [See editorial on pages 1893-9, this issue.] Cancer 1999;86:2006-13. (C) 1999 American Cancer Society.