Congestive Heart Failure (CHF) During Induction In ACUTE Promyelocytic Leukemia (APL) Patients

APL is a highly curable malignancy with cure rates of greater than 90% in most co-operative group trials. Population-based studies show that the survival is only about 65-70% with up to 30% early deaths. The most common reasons of early deaths are bleeding, differentiation syndrome (DS) and infection. Differentiation syndrome is very peculiar to this disease and potentially fatal unless recognized early. The wide variety of clinical presentations associated with DS might lead to delay in diagnosis in some patients which may lead to poorer outcomes. European Leukemia Net recommendations suggest that congestive heart failure (CHF) is one of the presenting features of DS and most of the reports on cardiac abnormalities focus on pericardial effusion. Cardiac stunning is only briefly reported in the literature. Cardiac stunning might be a result of cytokine storm attributable to tumor lysis in addition to being part of the DS. Here we report the incidence of CHF in patients undergoing induction for APL.

We performed a retrospective chart review on patients diagnosed with APL who received induction between December 1, 2004 and July 31, 2013 at Georgia Regents University and also patients who were referred to us from surrounding treatment centers with whom we co-manage these patients. Baseline and follow up ejection fractions (EF) were recorded by echocardiogram or nuclear medicine scan. We evaluated patients who had a drop in EF during the induction period.

41 consecutive patients with APL with normal ejection fraction at diagnosis were evaluated. 1 patient refused treatment and was excluded. 38/40 patients received idarubicin and ATRA remission induction and 2 patients received Arsenic and ATRA. There were seven deaths during induction phase of treatment In the surviving patients, 10 patients had a repeat ECHO during the first 30 days of induction phase for suspected cardiomyopathy. 5 patients (15.1% of surviving patients) demonstrated a decrease in EF and all five were in the anthracycline group. The age range of patients with drop in EF was 30-75 years. Absolute drop in EF was between 10- 35%. Only one patient had mild elevation in troponins while others had no elevation. 3 out of the 5 patients had significant DS. Of the surviving patients, 4 out of 5 patients recovered their EF completely with one patient recovering partially to 45-50% (from 20-25%).

Anthracyclines, along with ATRA, are still the mainstay of treatment for this curable malignancy. Although the incidence of cardiac abnormalities is described with repeated courses of anthracyclines, a single dose of anthracyclines can also play a role in cardiac injury. The highly inflammatory state present during the early treatment of APL might also play a role in cardiac injury resulting in higher number of patients with decreased EFs. DS clinical presentation most commonly involves dyspnea and edema, which are also symptoms of heart failure. Prompt cardiac evaluation should be undertaken to rule out congestive heart failure as an early start to therapy will lead to improved outcomes.

Awan:Lymphoma Research Foundation: Research Funding; Spectrum Pharmaceuticals Inc.: Speakers Bureau. Jillella:Lymphoma Leukemia society: Research Funding. Kota:Teva: Speakers Bureau; Ariad: Advisory board, Advisory board Other.