Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients

The clinical significance of complex chromosome aberrations for adults with acute myeloid leukaemia (AML) was assessed in 920 patients with de novo AM L who were karyotyped and treated within the German AML Cooperative Group ( AMLCG) trials. Complex chromosome aberrations were defined as three or more numerical and/or structural chromosome aberrations excluding translocation s t(8;21)(q22;q22), t(15;17)(q22;q11-q12) and inv(16)(p13q22). Complex chro mosome anomalies were detected in 10% of all cases with a significantly hig her incidence in patients greater than or equal to 60 years of age (17.8% v s. 7.8%, P < 0.0001). Clinical follow-up data were available for 90 patient s. Forty-five patients were < 60 years of age and were randomly assigned to double induction therapy with either TAD-TAD [thioguanine, daunorubicin, c ytosine arabinoside (AraC)] or TAD-HAM (high-dose AraC, mitoxantrone). Twen ty-one patients achieved complete remission (CR) (47%), 20 patients (44%) w ere non-responders and 9% of patients died during aplasia (early death). Th e median overall survival (OS) was 7 months and the OS rate at 3 years was 12%. Patients receiving TAD-HAM showed a significantly higher CR rate than patients receiving TAD-TAD (56% vs. 23%, P = 0.04). Median event-free survi val was less than 1 month in the TAD-TAD group and 2 months in the TAD-HAM group, respectively (P = 0.04), with a median OS of 4.5 months vs. 7.6 mont hs (P = 0.13) and an OS after 3 years of 7.6% vs. 19.6%. Forty-five patient s were greater than or equal to 60 years of age: 28 of these patient were t reated for induction using one or two TAD courses and 17 cases received TAD -HAM with an age-adjusted reduction of the AraC dose. The CR rate was 44%, 38% were non-responders and 18% experienced early death. The median OS was 8 months and the OS rate at 3 years was 6%. In conclusion, complex chromoso me aberrations in de novo AML predicted a dismal outcome, even when patient s were treated with intensive chemotherapy. Patients under the age of 60 ye ars with complex aberrant karyotypes may benefit from HAM treatment during induction. However, long-term survival rates are low and alternative treatm ent strategies for remission induction and consolidation are urgently neede d.