Comorbidity and performance status in acute myeloid leukemia patients: a nation-wide population-based cohort study.

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.

Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial.

This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a transfusion need of 4 units over 8 weeks were included. Aza 75 mg m(-2) d(-1), 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations.