Abstract

Trisomy 8 (+8) occurs in about 8–13% of patients with acute myeloid leukemia (AML). However, so far the prognostic impact of this recurrent aberration is unclear. Additional prognostic factors and different consolidation therapies may influence prognosis in this disease entity.

Therefore, the German AML Intergroup analyzed 198 adult patients (median age 49 (17–60) years; 172 de novo and 26 secondary AML) with trisomy 8 treated between 1993 and 2002 in eight prospective German AML treatment trials. Patients with t(8;21), inv(16) or abn11q23 and an additional +8 were not included in the study. Clinical, diagnostic and laboratory data were reviewed for consistency and completeness before analysis by a central coordination center.

Ninety-two (46%) patients had +8 as a sole aberration, 39 (20%) had one additional secondary aberration and 67 (34%) had +8 within complex karyotypes with at least three independent abnormalities. Trisomy 8 was frequently accompanied by other trisomies (53/198), especially by +21 (16/198) or +22 (13/198).

Complete remission rate after two induction therapies was 62% for all patients. An additional +21 (odds ratio 0.17; 95% CI 0.05–0.57) and a secondary AML (odds ratio 0.38; 95% CI 0.16–0.90) were negative prognostic factors for treatment response. Only 25% of patients with an additional +21 reached CR criteria.

Disease free survival (DFS) was 18% and overall survival (OS) 19% after 5 years for all patients, respectively. Patients with +8 as a sole aberration had a 5-year OS of 20%, with one additional secondary aberration of 32% and with a complex karyotype of only 8% (p=0.005). All but one patient with an additional +21 died within the first two years (p<0.001).

Multivariate analysis revealed age (difference 10 years hazard ratio (HR) 1.30; p<0.001), an additional +21 (HR 2.32; p=0.004), a complex karyotype (HR 1.58; p=0.02) and logarithm of white blood cell count (WBC) (HR 1.41; p=0.01) as prognostic factors for overall survival and age (difference of 10 years HR 1.22; p=0.01) and a complex karyotype (HR 1.63; p=0.04) for disease free survival in all patients. Post remission therapy (i.e. high-dose Ara-C vs. autologous transplantation vs. conventional allogeneic transplantation) did not enter in the multivariate models. Looking on the group of patients with +8 as sole aberration only extramedullary disease (HR 2.05; p=0.02) influenced survival.

In conclusion, the data of this large cohort of patients indicate that AML with trisomy 8 is a heterogeneous entity. Neither allogeneic nor autologous transplantation proved superiority compared to high-dose cytarabine based consolidation therapy. For the majority of patients alternative therapeutic approaches are needed to achieve durable remissions in the future.

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