Therapeutic outcome in prognostic subgroups of de-novo acute myeloid leukemia (AML) and the role of the age factor. A study in 1834 patients of 16 to 84 years

Abstract

6552 Background: While 2/3 of pts with AML are 60 yrs of age or older their outcome is constantly inferior to that in younger pts. This difference is poorly understood and not explained by different incidences in prognostic factors. Though favorable karyotypes were less frequent (7% vs 23%) and unfavorable karyotypes more frequent (20% vs 10%) in older pts (Blood 2001;98:1312), MLL duplication was unfrequent overall (<5%) (Leukemia 2000;14:796), morphologic dysplasia did not prove as an independent factor (JCO 2003;21:256), and MDR1 did not predict for long- term outcome (Blood 1999;94:1086). No age relation was shown for FLT3, EVI1 or BAALC expression. Methods: We evaluated 1834 pts with de-novo AML including 750 pts of 60+ yrs and 1084 younger pts both concurrently treated in two consecutive trials. Chemotherapy was TAD-HAM (HAM, high-dose araC/ mitox) or HAM-HAM for induction, TAD for consolidation and reduced TAD for maintenance (JCO 2003;21:4496) randomly compared with intensified consolidation. Results: 72% of younger and 60% of older pts went into complete remission (p<0.001). By multivariate analysis we identified favorable and unfavorable karyotype, age, LDH and day 16 marrow blasts as independent factors predicting OAS, remission duration and RFS, while the treatment modifications did not reach significance. Favorable karyotypes were less frequent in the older pts (7% vs 14%) and unfavorable karyotypes more frequent (24% vs 20%) than in younger pts (p<0.001), being the only differences to the advantage of the younger group. The probability of ongoing remission at 4 years in the two age groups and the various prognostic subgroups are listed below. Similar differences as in remission duration were found in overall and relapse-free survival. Conclusions: Older age AML is a particular disease of unfavorable biology equally affecting the outcome across all prognostic subgroups defined so far. No significant financial relationships to disclose.