Race Influences the Response to Conventional Induction Chemotherapy in Asian Patients with Acute Myeloid Leukemia

Background

Though there has been significant improvement in the outcome of adult patients with acute myeloid leukemia (AML), much of this has been attributed to advance in supportive care. Response to therapy has been a key predictor of clinical outcome in patients with newly diagnosed AML. Published studies have identified prognostic factors in predicting treatment response for AML induction therapy but data is lacking in Asian population.

 

Objectives

To evaluate the response rates of conventional induction chemotherapy in patients with AML in a tertiary care hospital and to identify prognostic factors associated with primary resistant AML.  

 

Methods

This retrospective study included newly diagnosed AML patients who received conventional induction chemotherapy at Singapore General Hospital between January 1999 and June 2013.  Primary outcome of the study was to determine the response rates to treatment. Secondary outcomes included duration of CR, relapse rate, overall survival (OS), and pre-treatment prognostic factors associated with primary resistant AML. Primary resistant AML was defined as failure to achieve CR within two cycles of induction chemotherapy.

 

Results

A total of 391 patients, with a median age of 49 years (range 13 – 79), were included. The most common induction chemotherapy used was IA 3+7 (idarubicin 12mg/m²/day for 3 days and cytarabine 100mg/m²/day for 7 days), received by 98.7% of patients during first induction and 70% of patients during re-induction. Overall CR rate was 80.1%, with 62.7% and 15.6% of patients attaining CR after one and two cycles of induction chemotherapy respectively. In addition, relapse rates were similar in patients who achieved CR after one and two cycles of induction chemotherapy (42.4% vs. 40.9%, p=0.94). Of note, among patients requiring re-induction, there was no significant difference in the CR rates between the use of IA 3+7 and non-IA 3+7 regimen (p=0.45). About 10% (n=39) of patients had primary resistant AML, of which seven of them achieved CR with salvage chemotherapy and six relapsed later.

Multivariate analysis identified Malay race (OR: 18.6, 95% CI 3.3 – 105.4) and patients with adverse risks (OR: 17.2, 95% CI 3.1 – 97.3), defined by the European Leukemia Net (ELN) risk classification, as predictors for primary resistant AML. However, Malay race was not found to have a higher incidence of adverse risks compared to non-Malay (p=0.98).

Conclusion

The most significant finding from this study was that Malay race is associated with primary treatment resistance to conventional induction chemotherapy. Further studies may be warranted to identify other contributing factors and optimize induction treatment for this subgroup of patients.