Short-term cardiac toxicity of autologous hematopoietic stem cell transplant for multiple myeloma

Th e last two decades have seen tremendous progress in the treatment of multiple myeloma, including the use of high-dose melphalan (HDM) with autologous hematopoietic stem cell transplant (auto-HCT) and the availability of various novel agents [1]. Th e incidence of cardiotoxicity after HDM is not known, even though there have been case reports of cardiac arrhythmias with HDM [2,3]. In this study, we evaluated the incidence of cardiac adverse events (AEs) in 325 patients within 30 days of undergoing auto-HCT using HDM at M. D. Anderson Cancer Center for multiple myeloma between January 2006 and December 2009. We excluded 78 patients with concurrent immunoglobulin light chain amyloidosis (AL). In the group who experienced cardiac AEs, melphalan doses of 200 mg/m 2 (19 patients) and 180 mg/m 2 (one patient) were used. Similarly, melphalan doses of 200 mg/m 2 (215 patients), 180 mg/m 2 (six patients), 160 mg/m 2 (one patient) and 140 mg/m 2 (two patients) were used in the group without cardiac AEs. In two patients without cardiac AEs the melphalan dose was missing. All patients received granulocyte colony stimulating factor (G-CSF), 5 μ g/kg/ day from day 1 until the absolute neutrophil count (ANC) was 0.5 109/L for 2 consecutive days, as per departmental guidelines. Supportive care measures, including blood product transfusion and electrolyte and weight management were done as per institutional guidelines. Cardiac toxicity was defi ned as any cardiac AE reported from the day of administration of melphalan to day 30 after auto-HCT. Th ese cardiac AEs included congestive heart failure (CHF), arrhythmias, ischemic chest pain and sudden cardiac death. CHF was defi ned as any structural or functional cardiac disorder that impaired the ability of the ventricles to fi ll or eject blood, with associated symptoms of fatigue, dyspnea and fl uid retention. Sudden cardiac death was defi ned as cessation of cardiac activity leading to unresponsiveness and demise of the patient. Ischemic chest pain was defi ned as typical substernal chest pain that was precipitated by exertion, radiating to the jaw and the inner aspect of the arms or shoulders, and relieved by nitroglycerin. Prior cardiac history was defi ned as a history of coronary artery disease, arrhythmias, valvular heart disease or cardiac light-chain amyloidosis before auto-HCT. Th e primary endpoint of the study was to evaluate the incidence of cardiac AEs after HDM and auto-HCT. We also evaluated the variables that could aff ect cardiac AEs. Th ese variables included a prior history of hypertension, diabetes, tobacco smoking, prior chemotherapy, interval between diagnosis and auto-HCT, cardiac biomarkers (troponin and brain natriuretic peptide [BNP]) and echocardiogram. Cardiac biomarkers are routinely collected as a part of pre-transplant evaluation.