Acute myeloid leukemia (AML) may present with vascular phenomena, commonly manifested in the pulmonary and neurologic systems, and often attributed to leukostasis, thrombotic abnormalities as with acute promyelocytic leukemia (APL), and anemia. Myocardial infarction (MI) may be the initial presentation of these vascular changes, preceding a diagnosis of AML. We reviewed the incidence of MI in the setting of a new AML diagnosis, associated risk factors, and impact on overall survival (OS).
All patients diagnosed with AML at Cleveland Clinic between 2001 and 2012 who were also diagnosed with MI (either a ST-elevation MI or a non-ST-elevation MI with compatible cardiac biomarkers) at the time of AML diagnosis (median same day, range from 2 days before to 93 days after MI diagnosis) were identified (cases). We performed a case-control analysis in which MI patients were randomly matched 3:1 to non-MI patients based on gender, age at diagnosis (±5 years), year of diagnosis (±3 years), and if available, cytogenetics and etiology. Overall survival (OS) was the primary endpoint; also compared were MI risk factors (previous MI, hypertension, hyperlipidemia, and diabetes); complete blood count (CBC) characteristics (white count, hemoglobin, and platelets); and AML type (APL and non-APL). Statistical analyses included Fisher's exact, chi-square, and Wilcoxon rank sum test (patient characteristics and MI risk factors); and the logrank test and frailty models (OS).
Out of 774 AML patients, 12 (1.6%) presented with a MI: 54% were male and the median age at diagnosis was 61 years (range 19–94); 19% had one of more risk factors for MI (heart disease, hypertension, hyperlipidemia, and diabetes); 52% were non-smokers, 25% were former smokers, and 23% currently smoked. Most (71%) were newly-diagnosed, 24% had prior myelodysplastic or myeloproliferative neoplasms, 6% was therapy-related, and 6% had APL. Most (83%) received standard cytarabine-based induction therapy, and 67% achieved a complete remission. Median follow-up for patients still alive was 19.3 months. Of the patients presenting with MI, 11 of 12 have died with a median OS of 7.9 months, compared with a median OS of 13.1 months in the entire non-MI cohort (95% CI 11.0–15.1, p=.02). MI remained associated with worse OS in multivariable analyses (HR 1.71, 0.91–3.22, p=.09). In case-control analyses, controls had a median OS of 14.0 months compared to 7.9 months for MI cases (95% CI 8.7–26.6, p=.04 adjusting for the matching and number of comorbidities present, Figure). Factors associated with MI included previous MI (p=.01) and > 2 comorbidities (p=.02). Other MI risk factors, CBC characteristics, and APL compared to non-APL did not differ significantly between the two groups.
In conclusion, AML patients presenting with MI have a worse OS than non-MI AML patients. Preceding comorbidities place patients at greater risk for MI than leukemia-related factors.
Advani:Novartis: Research Funding. Maciejewski:Novartis: Research Funding. Sekeres:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
Asterisk with author names denotes non-ASH members.