LONG-TERM SURVIVAL AND DEVELOPMENT OF SECONDARY MALIGNANCIES IN PATIENTS WITH ACUTE MYELOID-LEUKEMIA TREATED WITH ACLARUBICIN OR DAUNORUBICIN PLUS CYTOSINE-ARABINOSIDE FOLLOWED BY INTENSIVE CONSOLIDATION CHEMOTHERAPY IN A DANISH NATIONAL PHASE-III TRIAL

In 1991 we reported the results from a prospective randomised phase 3 trial comparing 7 days continuous infusion of cytosine arabinoside (ar a-C) combined with either daunorubicin (DNR) or aclarubicin (ACR) as d irect i.v. injection for 3 days as induction chemotherapy (CT) for pat ients with de novo acute myeloid leukemia (AML) followed by early inte nsive consolidation CT with two alternating cycles of high-dose ara-C and two cycles of amsacrine plus etoposide, and finally 3 days of daun omycin plus 7 days of ara-C as administered for induction of remission . A total of 174 patients with de novo AML in the age group 17-65 year s were included. The patients have now been followed till death or for at least 7 years, and an evaluation of the longterm survival and the risk of developing secondary neoplasms has been made. The overall surv ival rate 5-years after diagnosis was 23%, and after 10 years 19%. No difference was found between the two treatment regimens in overall sur vival or disease-free survival (DFS). For the subgroup of 99 patients who achieved complete remission after one or two induction courses, 5- and 10-year survival rates were 35% and 31% respectively, with the hi ghest survival rates in the age group 17-39 years (57% at 5 years) as compared with 27% in patients aged 40-60 years (P=0.007). Seven second ary neoplasms were diagnosed simultaneously with or after the diagnosi s of AML indicating a standardized incidence ratio (SIR) of 3.41, (95% CI: 1.60-7.26). In three cases the secondary neoplasms were diagnosed simultaneously with the AML diagnosis and were for that reason comple tely unrelated to the chemotherapy administered for AML, as the psammo matous meningeoma diagnosed after only 8 months. The remaining three n eoplasms which developed subsequently did not significantly exceed the expected number, with a SIR=1.46 (0.47-4.57). Thus, no increased risk of solid tumors causally related to the intensive chemotherapy for de novo AML was observed. However, a generally increased risk of solid t umors In patients diagnosed simultaneously with the AML diagnosis seem s likely. Over 20% of the patients were alive and in complete remissio n 5 years after the AML diagnosis, and they have a high probability of surviving the next 5-year period.