Elderly Patients with Acute Myeloid Leukemia Are Not All the Same: Results of the Prospective DSIL AML96 Trial.

The majority of patients with acute myeloid leukemia (AML) are older than 60 years at diagnosis. However, treatment results for these elderly patients are still unsatisfactory. This is thought to be due to a more aggressive disease, preexisting co-morbidities or a decreased tolerance for intensive treatment approaches. As for younger patients there is growing evidence that elderly AML patients may be divided into prognostic subgroups. So far data on prognostic factors in this group of patients are still sketchy. Between February 1996 and March 2005 a total of 827 elderly AML patients with a median age of 67 (61–87) years were treated within the prospective AML96 trial of the German Study Initiative Leukemia (DSIL). 643 patients had de novo and 184 patients secondary disease. All patients were scheduled to receive a double induction therapy with Daunorubicin and Ara-C (DA3+7). The consolidation therapy consisted of one course of m-Amsacrine and intermediate-dose (10g/m²) Ara-C. 265 (32%) patients reached CR criteria after double induction therapy. Forty-two patients (5%) had only a PR, 307(37%) displayed refractory disease, 126(15%) died during induction therapy and 77(10%) received only one course of induction therapy due to severe toxicity. Out of the 265 patients in CR 120 (45%) patients received the consolidation course. The strongest independent prognostic factors for achieving a CR were less than 10% blasts in the day 15 bone marrow, the presence of a NPM mutation or a low-risk karyotype (p<0.0001 each). The 3-year overall (OS) and relapse-free survival (RFS) rates were 18% for all patients and 17% for all patients in CR, respectively. In the multivariate analysis the strongest prognostic factors for survival were age, LDH and cytogenetics (p<0.0001 each). Using these three parameters a prognostic model for survival was established. Patients older than 70 years with intermediate- or high-risk cytogenetics and a high LDH level at diagnosis (n=213) had a 3-year OS of only 9%, whereas patients with low-risk cytogenetics or patients with intermediate-risk cytogenetics, younger than 70 years and a low LDH level (n=237) had a 3-year OS of 32%. All other patients (n=377) had an intermediate 3-year OS of 15% (p<0.0001). In conclusion, elderly AML patients can be stratified into prognostic groups. AML patients older than 70 years with high LDH levels and intermediate- or high-risk cytogenetics at diagnosis do not profit from conventional chemotherapy.