Long Term Follow up of the AML97-Study for Patients with AML Older Than 60 Years: A Study of the East German Hematology and Oncology Study Group (OSHO)

The incidence of acute myeloid leukemia (AML) is age-dependent with the majority of patients (pts) being older than 60 years at diagnosis. Treatment of these pts needs to be well balanced between sufficient efficacy and tolerable toxicity. Here, we report long term follow-up of the OSHO AML97 study. Pts with AML older than 60 years were registered after informed consent and received age-adapted intensive chemotherapy treatment (curative arm; induction therapy with AraC 2 g/m² iv day 1, 3, 5, 7 and mitoxantrone 10 mg/m² iv day 1 to 3 to induce complete remission (CR), followed by 2 consolidation courses with AraC 240 mg/m² iv day 1 to 5 and mitoxantrone 10 mg/m² iv day 1 to 2), low dose chemotherapy (palliative arm; idarubicin 10 mg po day 1 and either thioguanine 40 mg po day 1-5, or AraC 80 mg sc day 1-5 or etoposide 100mg po day 1-5) or supportive therapy (best supportive care including transfusions). A total of 618 pts were enrolled (curative arm n=471, palliative treatment n=115 and supportive therapy n=32 pts). In the curative arm, CR was obtained in 66.8% of pts. Treatment related mortality (TRM) was 11.2% after induction and 4.5% after consolidation I, respectively. Median overall survival for all pts in the curative arm was 12 months, event free survival (EFS) at 12 years was 0.11±0.02%. In multivariate analysis, cytogenetics at diagnosis was the most important prognostic factor for CR (p=0.001). With a median follow up of 10 years (range 0.1 - 11.8) probability of overall survival (OS) at 5 years was 0.48±0.11; 0.13±0.03; 0.10±0.04 and 0.08±0.03 for pts with favorable, normal, other and unfavorable cytogenetics. Median survival for pts treated with palliative chemotherapy was 54 days.

In conclusion treatment of older AML pts with an intense dose of AraC in the induction therapy is feasible and able to induce high rates of CR. Nevertheless, despite the high CR rate in this setting OS and EFS are still low. However, importantly, this does not apply for patients with favorable cytogenetics. This result also confirms the need for cytogenetic analysis to be performed in all pts older than 60 years potentially eligible for intensive induction therapy. The treatment results with palliative chemotherapy are disappointing. These results reported here need to be set in relation with the new therapeutic modalities for AML including epigenetic and molecular therapies.