Our results support that de novo AML, sAML, and tAML are biologically and prognostically distinct subtypes of AML. Patients with non-MDS-sAML have dismal outcomes, independent of age and cytogenetics. Previous myeloid disorder, age, and cytogenetics are crucial determinants of outcomes and should be integrated in treatment recommendations for these patients.

As the world population ages, the comorbidity burden in acute myeloid leukemia (AML) patients increases. Evidence on how to integrate comorbidity measures into clinical decision-making is sparse. We determined the prognostic impact of comorbidity and World Health Organization Performance Status (PS) on achievement of complete remission and mortality in all Danish AML patients treated between 2000 and 2012 overall and stratified by age. Comorbidity was measured using a modified version of the Charlson Comorbidity Index, with separate adjustment for pre-leukemic conditions. Of 2792 patients, 1467 (52.5%) were allocated to intensive therapy. Of these patients, 76% did not have any comorbidities, 19% had one comorbid disease and 6% had two or more comorbidities. Low complete remission rates were associated with poor PS but not with comorbidity. Surprisingly, among all intensive therapy patients, presence of comorbidity was not associated with an increased short-term mortality (adjusted 90 day mortality rate (MR)=1.06 (95% confidence interval (CI)=0.76-1.48)) and, if any, only a slight increase in long-term mortality (91 day-3 year adjusted MR=1.18 (95%CI=0.97-1.44). Poor PS was strongly associated with an increased short- and long-term mortality (adjusted 90 day MR, PS⩾2=3.43 (95%CI=2.30-5.13); adjusted 91 day-3 year MR=1.35 (95%CI=1.06-1.74)). We propose that more patients with comorbidity may benefit from intensive chemotherapy.

In a Danish bi-regional registry-based study, we conducted an analysis of the incidence and clinical importance of secondary acute myeloid leukaemia (AML). In a total of 630 cases of AML, we found 157 (25%) cases of secondary AML. The secondary leukaemia arose from MDS (myelodysplastic syndrome) in 77 cases (49%), CMPD (chronic myeloproliferative disorder) in 43 cases (27%) and was therapy-related AML (t-AML) in 37 cases (24%). Median age at diagnosis of AML was 69 yr in secondary cases when compared to 66 yr in de novo cases (P = 0.006). In univariate analyses, secondary AML was associated with an inferior complete remission (CR) rate (P = 0.008) and poorer overall survival (OS, P = 0.003) whereas in complete remitters, disease-free survival (DFS) of secondary cases was equal to that of de novo cases. Interestingly, in all further analyses of CR-rates, OS and DFS, when correcting for the influence of age, cytogenetic abnormalities, performance status and leucocyte count (WBC), presence of secondary AML completely lost prognostic significance. We conclude that the presence of secondary AML does not per se convey an unfavourable prognosis and that patients with secondary AML should be offered the chance of benefiting from treatment according to current frontline AML protocols.