Cardiomyopathy Following High Dose Melphalan Conditioning Prior to Autologous Peripheral Blood Stem Cell Transplantation for Multiple Myeloma and Primary Amyloidosis

Abstract

High dose melphalan (HDM) is a commonly utilized conditioning regimen prior to autologous peripheral blood stem cell transplantation (PBSCT) for multiple myeloma and primary amyloidosis. Although cardiotoxicity from this regimen has not been described, there are multiple anecdotal cases of transient cardiomyopathy following HDM in the Mayo Clinic transplant experience. Thus, we reviewed our experience to determine the frequency of cardiomyopathy in this setting. From our database of all patients undergoing autologous PBSCT for myeloma or amyloidosis from 1989-2009, we identified those with echocardiograms performed before and within 4 months of PBSCT, and reviewed these for evidence of cardiomyopathy, defined as a decrease in left ventricular ejection fraction (LVEF) of ≥ 10% to a value of ≤ 50%. Charts of patients meeting these criteria were reviewed to determine conditioning regimen, pre-existing cardiac risk factors and other potential causes of cardiomyopathy to determine the association between the cardiomyopathy and HDM. Of 1476 patients (1050 myeloma; 426 amyloidosis) who received HDM as a component of conditioning prior to PBSCT, 407 had echocardiography before and within 4 months after PBSCT, and 40 (2.7%) met criteria for cardiomyopathy. When accounting for other risk factors, HDM was felt to be a probable cause of cardiomyopathy in 16 patients, a possible cause in 18, and an unlikely cause in 6. Cardiomyopathy was noted more frequently in patients undergoing PBSCT for amyloidosis (23/426, 5.4%) than myeloma (17/1050, 1.6%). All 23 patients with amyloidosis received HDM alone as conditioning (dose range 140-200 mg/m2). Fifteen of the 17 myeloma patients received HDM alone as conditioning (dose range 140-200 mg/m2), with two patients receiving HDM in concert with total body irradiation and ibritumomab, respectively. The mean pre-PBSCT LVEF in this cohort was 59% (range 42-70%), which decreased to a mean of 38% (range 15-50%) following PBSCT. Diagnosis of cardiomyopathy was made within 30 days of PBSCT in 65% (26/40) of patients. Follow up echocardiography was performed in 26 patients, with 15 showing improvement in LVEF to ≥ 50%. To our knowledge, this is the first series to report cardiomyopathy following HDM conditioning. Further work should focus on identifying pre-transplant variables which may predispose patients to cardiotoxicity following conditioning with HDM.