Incidence and Clinical Features of Acute Promyelocytic Leukemia In a Population-Based Canadian Cohort

Acute promyelocytic leukemia (APL) is a rare malignancy whose causes and epidemiology are not well known. The incidence of APL in the United States was estimated to be 0.22 cases per 100,000 population, and a higher incidence has been suggested in specific geographic or ethnic sub-groups. However, clinical and epidemiological data on APL arise primarily from clinical trials and single centre experiences rather than population-based data, which may lead to selection bias. We studied a cohort of APL cases in a well defined population using the diagnostic gold standard of polymerase chain reaction (PCR) testing.

The Canadian province of Manitoba, with a population of 1.2 million, has a single referral centre for the definitive diagnosis and clinical care of all acute leukemia patients. Only one laboratory is capable of performing PCR based testing for the PML-RARA fusion gene product. We examined consecutively diagnosed patients with APL based on PCR testing from January 1999 until July 31 2010 in order to determine the incidence, clinical characteristics, and outcomes of patients with APL.

Over the 11.5 year period of observation, 24 patients were diagnosed with APL. Based on the 2006 Canadian census, the annual incidence of APL in Manitoba is thus 0.18/100,000 population. These cases did not appear to be distributed evenly, with an average of 1.1 cases diagnosed annually between 2002 and 2008 compared to six cases diagnosed in the most recent period between 2009 and 2010 (relative to 2002–2008, incident rate ratio (IRR) 2.61, p = 0.075) and ten cases diagnosed between 1999 and 2001 (IRR 2.94, p = 0.023). Symptomatic CNS disease at diagnosis was present in 3 (12.5%) patients. Thirteen patients developed differentiation syndrome during the course of their therapy (54.1%). In all but one patient, ATRA was able to be successfully resumed. Ten patients presented with DIC (41.7%).

In this population-based study, we noted episodic clustering of new cases and a relatively high proportion of CNS disease at diagnosis. While these observations may be due to normal fluctuations in the patterns a rare disease, this could also suggest an underlying environmental trigger. Additional investigation is required to confirm or refute this hypothesis, due to the relatively small numbers in this cohort. The high rate of CNS disease suggests that this finding maybe more common than previously thought. As the pathogenesis of APL remains unclear, these observations deserve additional epidemiological investigation in larger cohorts.

Kumar:Celgene: Membership on an entity's Board of Directors or advisory committees.