Intensification of Induction by High-Dose AraC and Outcome in Older Patients with De-Novo Acute Myeloid Leukemia (AML) and Subsets.

As recently reported modifications, dose or duration of treatment had no impact on outcome of AML in older patients (Burnett et al. Blood 106: 162a, 2005). We therefore evaluated 764 patients 60 years of age or older and their various prognostic subgroups in the 1992 and 1999 mulitcenter randomized trials by the German AMLCG where patients received uniform postremission consolidation by one course of TAD (standard dose thioguanine, araC, daunorubicin) and maintenance by monthly 5 day courses of reduced TAD. For maximum homogeneity this analysis was restricted to de-novo AML and to patients with known karyotype. Before treatment started, patients were assigned to induction treatment by either TAD followed by HAM (HAM, high-dose araC 1g/m2x6 / mitoxantrone 10mg/m2x3), or to induction by two courses of HAM. The second induction course (HAM) was given to only patients with 5% or more residual bone marrow blasts. Therapy administered to the two randomized groups differed by a factor 2 in their araC dose. Despite this difference in treatment intensity patients in the two arms show similar response rate, overall survival (OS), ongoing CR, and relapse-free survival (see table). The same similarity in outcome as for de-novo AML overall is true for established prognostic subgroups as listed below. Conclusion: Intensification of induction therapy by high-dose araC has no effect on outcome in older age de-novo AML. Since potential influences other than the randomized treatment were minimized, present results do not support a risk adapted intensification strategy. | | TAD-HAM | HAM-HAM | P | TAD-HAM | HAM-HAM | P | |:---------------------- | ------- | ------- | --- | ------- | ------- | --- | | | OS 4y % | OS 4y % | | CR 4y % | CR 4y % | | | Total | 18 | 13 | .28 | 22 | 22 | .53 | | Favorable Karyotype | 17 | 16 | .48 | 41 | 33 | .82 | | Intermediate Karyotype | 24 | 18 | .31 | 24 | 26 | .38 | | Unfavorable Karyotype | 4 | - | .81 | - | - | .37 | | LDH ≤ 700U/L | 21 | 13 | .86 | 23 | 24 | .47 | | LDH > 700U/L | 12 | 10 | .07 | - | 16 | .27 | | WBC ≤ 20x103/ccm | 21 | 11 | .91 | 22 | 21 | .81 | | WBC > 20x103/ccm | 15 | 16 | .08 | 22 | 26 | .19 | | Day 16 Blasts < 10% | 26 | 16 | .87 | 23 | 22 | .81 | | Day 16 Blasts ≥ 10% | 14 | 8 | .28 | 18 | 19 | .26 |