Excessive Early Death after Intensive Chemotherapy for Acute Myeloid Leukemia Occurs in Patients over 65 Years with High Co-Morbidity, and in Patients over 50 Years with High Co-Morbidity When Postponed Early Death Is Included

Background Early death (ED) after intensive induction chemotherapy is defined as death by any cause occurring in the first 30 days after start of chemotherapy. ED significantly contributes to poor outcome in elderly acute myeloid leukemia (AML) patients. The presence of co-morbidity, as determined with the hematopoietic stem cell transplantation co-morbidity index (HCT-CI) has been shown to predict ED in patients >60 years, with HCT-CI scores of 0, 1-2 or ≥3 resulting in ED rates of 3%, 11% and 29%, respectively (Giles et al. BJH 2007). This makes the HCT-CI an ideal tool to distinguish elderly AML patients fit for intensive chemotherapy from those that may benefit more from less intensive alternative treatments.

However, the number of studies on HCT-CI and ED risk are limited and have only reported on ED in relation to age as a categorical valuable (age below or over 55-60 years). Data on the usability of the HCT-CI for ED prediction in different age cohorts are not available. Therefore, we performed a retrospective study to assess the value of the HCT-CI in predicting ED in different age cohorts in order to improve treatment decision in AML.

Methods We retrospectively analysed ED risk in relation to HCT-CI in different age cohorts in 260 AML patients treated with intensive chemotherapy at our institution between 2003 and 2015. Median age of the patients was 59 years (range 19-79). All patients received intravenous cytarabine, mostly continuously in a dose of 100-200 mg/m2 per day for 7-10 days, in combination with different anthracyclines.

Results ED occurred in 17 patients (6.5%) after a median of 18 days (range 1-29) from start of chemotherapy. ED was low in patients <=50 years, irrespective of HCT-CI score. Only patients aged >65 years with a HCT-CI >=3 showed an excessive ED rate of 22%. All other patient cohorts showed moderately increased ED rates, never exceeding 10%.

In addition to the 17 patients that died before day 30, another 11 patients without refractory disease died after day 30 before the second chemotherapy cycle. These were mainly patients aged 51-65 years that had been admitted to the Intensive Care, which had postponed their ED. By including postponed ED into ED, ED risk increased to 20% in patients aged 51-65 years with HCT-CI >=3. Mortality in patients with HCT-CI 0-2 remained maximally 10% in all age groups.

Conclusion In our hands, only patients aged over 65 years with high co-morbidity (HCT-CI >=3) have an excessive risk for ED (>20%) when treated with intensive chemotherapy. In this patient group alternative therapies should be considered. Intensive care admission results in postponement of ED after day 30 in a considerable proportion of patients, especially in those aged 51-65 years. By including postponed ED (defined as death in remission after day 30 but before second induction) into ED, all patients aged over 50 years with high co-morbidity (HCT-CI >=3) show excessive risk for ED (>20%) when treated with intensive chemotherapy.