Population-based disparities in survival among patients with core-binding factor acute myeloid leukemia: A SEER database analysis

Abstract

We performed a retrospective population-based study using the SEER database to assess survival trends in CBF-AML between 2000 and 2010. Median OS increased from 16 months in 2000–2002 to 25 months in 2006–2008 (P = 0.002). The 3-year OS rate for patients with inv(16) was 57.3%, but in t(8;21) was only 35.5%. Patients aged 75–84 had worse survival than patients aged 15–44 (HR 5.61, P = 0.0002). Black race was associated with higher mortality (HR 1.50, P = 0.03). Compared to clinical trial outcomes, CBF-AML survival is poorer in the general population, particularly among African Americans and the elderly, and in t(8;21) compared to inv(16) AML.

Introduction

Acute myeloid leukemia (AML) with a translocation between chromosomes 8 and 21 (t(8;21)) or a pericentric inversion of chromosome 16 (inv(16)/t(16;16)) is associated with alterations in the core binding factors RUNX1 (also known as CBFA2 or AML1) and CBFB [1], [2], [3], [4]. Patients harboring these alterations carry a more favorable prognosis when given intensive chemotherapy regimens[5], [6], [7], [8], and excluding acute promyelocytic leukemia, have the best long term survival reported among AML subtypes. Although the group of patients with core-binding factor AML (CBF-AML) is relatively small – only approximately 7–12% of patients with AML carry the t(8;21) or inv(16) abnormality [5], [9] – their identification is critical as it significantly impacts their subsequent management and prognosis. Nonetheless, despite a favorable prognosis associated with CBF-AML overall, certain small subgroups continue to have poorer outcomes [10], [11], [12], [13], [14], [15].

Multicenter cooperative group trials report 5-year overall survival (OS) rates approximating 45–66% among patients with CBF-AML [14], [15], [16], [17]; much less is known about an unselected patient population treated outside of a clinical trial in the current era. The Surveillance, Epidemiology, and End Results (SEER) database is a population-based database maintained by the National Cancer Institute (NCI); it captures 28% of the US population based on the 2010 US Census. Several previous analyses have used SEER data to assess population-level trends in cancer survival and incidence among patients with acute myeloid leukemia in the United States, but none to date have looked specifically at CBF-AML [18], [19], [20], [21]. It is not currently known whether the favorable outcomes seen in clinical trials for CBF-AML are achieved at the population level.

This analysis presents outcomes of the largest cohort of unselected patients with CBF-AML reported to date. We assessed survival trends at the population level in order to determine their uniformity with data from previous clinical trials, and to identify specific subgroups with relatively poor outcomes among all patients with CBF-AML.