TIMED SEQUENTIAL CHEMOTHERAPY FOR ADVANCED ACUTE MYELOID-LEUKEMIA

Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1-3 , etoposide on days 8-10 and cytarabine on days 1-3 and 8-10, was admi nistered to 240 patients with advanced acute myelogenous leukemia (AML ). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47 % (CI: 38-55%) of refractory patients and 78% (CI: 70-86%) of late fir st relapse patients (p < 0.0001). Thirty percent of patients did not r espond to therapy and 9% died from toxicity. Median duration of neutro penia was 32 days and of thrombocytopenia 29 days. Severe non hematolo gic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell tra nsplantation in 17 and allogeneic transplantation in 20. Median surviv al of patients who were not transplanted was 7 months with 13% (CI: 7- 19%) survival at 5 years. Median disease-free survival (DFS) was 9 mon ths with 13% (CI: 6-20%) DFS at 5 years. Previous refractoriness was t he main factor associated with poor prognosis for achieving CR, DFS an d survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive postr emission therapy. These results confirm initial reports on TSC and sho w that some patients with first relapse off therapy can enjoy prolonge d DFS using chemotherapy only.