Pre‐anthracycline echocardiogram rarely changes treatment strategy in acute myeloid leukemia
Authors: John Ogden, Jennifer Yui, Walid Ali, Mythri Mudireddy, Aref Al‐Kali, Mrinal Patnaik, Naseema Gangat, Michelle Elliott, William Hogan, Christopher Hook, Alexandra Wolanskyj‐Spinner, Animesh Pardanani, Hector Villarraga, Mark Litzow, Ayalew Tefferi, Kebede Begna
Journal: American Journal of Hematology (2018)

The current standard treatment of acute myeloid leukemia (AML) includes anthracyclines and cytarabine. Increasing doses of anthracyclines are known to cause cardiotoxicity especially with individuals who have risk factors or previous exposure to chemotherapy and/or radiation.1 Higher doses of anthracycline (>550 mg/m2 of adriamycin or >450 mg/m2 of daunorubicin) are associated with an unacceptable heart failure rate of more than 30%.2 Echocardiogram is invariably done at baseline in all patients with acute myeloid leukemia, in particular prior to anthracycline exposure. The objective of this study is to assess the frequency with which pre-induction cardiac function evaluation leads to a change in therapeutic plan with avoidance of anthracycline use. After Mayo Clinic IRB approval, patients with an echocardiogram and a diagnosis of AML were identified from the AML database. Echocardiogram (echo) is the commonest method of evaluating pre-induction cardiac function. All available echo results within 30 days of the diagnosis of AML were collected regardless of the eventual type of induction chemotherapy received. The echo results included left ventricular ejection fraction (LVEF) and any reported diastolic dysfunction. Abnormal results considered included low LVEF (less than 50%) and diastolic dysfunction. The type of therapy given was meticulously collected in those who were identified to have abnormal echo result so as to identify change in treatment decision. Six hundred sixty-seven patients with a diagnosis of AML and an echo shortly after diagnosis were identified (Figure 1). Twenty-nine (4%) patients were found to have a LVEF below 50%. The median (range) age was 68 (18–82) years, 23 (79%) were males. Of these 29 patients, 20 of them were not being considered for anthracycline-based therapy, and their echo were done for alternate reasons stemming from other comorbidities such as congestive heart failure or coronary artery disease. Of the remaining 9 patients, in 4 cases abnormal echo (<50% LVEF) result did not change the planned anthracycline-containing chemotherapy regimen. These included: a 24 years old with LVEF of 48% who received 3 + 7 (anthracycline and cytarabine); a 65 years old with LVEF of 46% planned to receive 3 + 7, but received one day of daunorubicin because of hyperbilirubinemia; an 18 years old with LVEF of 48% in the setting of systemic inflammatory response syndrome (SIRS) and his LVEF improved to 61 after the SIRS was addressed and received 3 + 7; and the fourth one a 75 years old with secondary AML with LVEF of 45%-50%; who died prior to receiving a planned 3 + 7 regimen due to pulmonary complications. All patients with AML and echo. Only 5 (0.7% =5/667) patients had their treatment changed to alternative therapy due to concern for cardiotoxicity. These included: (1) a 57-year old who presented with blastic crisis with spontaneous tumor lysis and acute renal failure who was found to have LVEF of 31% and was treated with cytarabine only; (2) a 72-year old with secondary AML from myelofibrosis found to have LVEF of 39% and treated with cladribine; (3) a 71-years old with chronic myeloid leukemia (CML) and blastic crisis who was found to have a LVEF of about 39% but was found to be not a candidate for 3 + 7 due to other reasons; (4) an 82-year old with secondary AML whose echo showed 30%-35% LVEF and treated with azacytidine because of co-morbidity; and (5) a 70-year old with secondary AML and LVEF of 48% treated with cytarabine and etoposide. All those with LFEF less than 50% were either older (≥70 years old), or presented in blastic crisis. In the remaining 20 patients with low LVEF, the echo was done for other reasons not related to decisions with regard to chemotherapy choice. With aggressive treatment of acute leukemia, it is generally recommended to measure pre-induction left ventricular function with echo or multigated acquisition (MUGA) scan especially when there is a consideration to give anthracycline combination chemotherapy. The NCCN guideline is not stringent and recommends evaluation of myocardial function in those with symptoms of cardiac dysfunction or those who are exposed to cardiotoxic drugs or radiation exposure to the thorax.3 Thus far no clear predictive factors have been found that may help to identify individuals with higher risk of anthracycline-induced cardiotoxicity other than the usual risk factors like previous use of anthracycline and radiotherapy. Modification of anthracycline administration such as prolonged infusions, encapsulation, or combining with dexrazoxane (modulator of doxorubicin toxicity) or using different anthracycline have shown marginal benefit and are rarely used in acute leukemia or fail to decrease the long-term complication of anthracycline cardiotoxicity.4 The main approach has been to limit the dose to less than the maximum dose. In this study, we have identified only 5/667 (0.7%) patients where anthracycline is avoided as a result of concern for cardiotoxicity because of low LVEF. Those cases are older individuals or presented with blastic crisis. The notion that all patients need to have pre-anthracycline cardiac evaluation has been challenged in the management of various solid tumors including breast cancer.5 Similar findings and recommendation not to order pre-anthracycline echocardiogram were suggested in patients with non-Hodgins lymphoma.6 In conclusion, pre-induction echocardiograms evaluation rarely avoids anthracycline exposure in AML. Its use may be limited to those with advanced age, multiple comorbidities, and those presenting in blast crisis. This may save healthcare dollars without affecting the quality of care. Nothing to report.