Intensive Chemotherapy Is Not Recommended for Patients with AML or High-Risk MDS Aged over 60 Years with Complex Karyotype Anomalies.

Background: Intensive chemotherapy for patients with MDS or AML aged over 60 years still is a matter of debate. Although there are some patients with long-term survival after intensive chemotherapy, it is discussed controversially how to treat old patients with AML or high-risk MDS.

Methods: Between 1991 and 2003, 158 patients with MDS or AML underwent intensive chemotherapy with either Ida-Ara-C or TAD, followed by a second course of Ida-Ara-C or TAD, and followed by 2 years maintenance chemotherapy at our institution. Patients were either followed up until relapse, death or to July, 31.th.2004. Median time of follow up was 14 months.

Results: Median age at diagnosis was 67 years (60–78). There were 92 males and 66 females. In 101 patients, initial karyotype was available. 51 patients had a normal karyotype and in 50 patients an abnormal karyotype could be detected, 26 of whom had a complex karyotype.

94 patients (60%) entered complete remission (CR), 7 patients achieved partial remission (PR), 41 patients failed to respond (26%), and 16 patients succumbed within 4 weeks after the beginning of the induction therapy (10%). Patients with a normal or non-complex karyotype entered CR in 72%, whereas only 34% of patients with complex karyotype achieved CR (p=0.001). 86 (54%) patients received a consolidation therapy with another course of Ida-Ara-C or TAD. 20 patients received at least three courses of maintenance chemotherapy.

Median survival of the entire group was 15 months. At the time of analysis, only 19 patients were still alive. Patients with normal karyotype had a median survival of 19 months, as compared to 5 months in patients with abnormal karyotype (p<0.00005). Patients with a complex karyotype had a median survival of 4 months only (p=0.00005).

Two years after the beginning of the treatment, only 27% of the patients were still alive. A very small group of patients (n=9) achieved long-lasting remission of more than 3 years. 20 patients died in CR due to infectious complications during the consolidation chemotherapy or due to causes not related to the disease. The initial karyotype and entering CR after induction chemotherapy could be identified as the only prognostic parameters for predicting survival within in entire group. In a multivariate analysis, initial karyotype was the only independent predictive parameter.

Conclusions: Intensive chemotherapy is not recommended for patients with AML or high-risk MDS aged over 60 years with complex karyotype anomalies, because of a very poor prognosis, due to low CR rates and early relapses. Alternative treatment strategies, like deacetylating agents or demethylating agents should be performed for those patients.