Cardiac Toxicity and Non-Relapse Mortality in Patients with Low Left Ventricular Ejection Fraction Undergoing Stem Cell Transplantation.

Abstract

BACKGROUND: Both autologous and allogeneic stem cell transplantation (SCT) are potentially curative treatment options for patients with hematologic malignancies. Due to a high risk of regimen-related toxicity, only patients with satisfactory organ-system function are considered eligible for this treatment. A low left ventricular ejection fraction (LVEF) of ≤ 45% is considered to be a major risk factor for post-transplant cardiac toxicity and non-relapse mortality (NRM). However, many patients with advanced hematologic malignancies and low LVEF can potentially benefit from this therapy. To address this issue, we studied the incidence of cardiac toxicity and NRM in 89 patients with low LVEF undergoing SCT. METHODS: We performed a retrospective analysis on 89 patients with impaired cardiac function, who underwent an autologous (33 patients) or allogeneic (56 patients) SCT between January 2000 and February 2006 at our institution. Pre-transplant evaluation included bidimensional echocardiogram and an electrocardiogram. Cardiac toxicity was defined as congestive heart failure (CHF), atrial/ventricular arrhythmia or acute myocardial ischemia. In the allogeneic group, 22 patients received a myeloablative (16 busulfan-based, 6 TBI-based), while 34 patients received a fludarabine-based reduced-intensity preparative regimen. Twenty-three patients (41%) received allo SCT from an unrelated donor. The majority of patients in the autologous group received BEAM (with rituximab or IL-2) based regimen (24 patients) and 6 patients received high dose melphalan. RESULTS: 57% of the allogeneic transplants were for acute leukemia. 76% of autologous transplant recipients had Hodgkin’s or non-Hodgkin’s lymphoma. Baseline LVEF, within 30 days prior to SCT, ranged from 20 to 45%. After a minimum of 6-month follow up, cardiac toxicity was seen in 6 patients in the auto SCT group and 6 patients in the allo SCT group (13%). In 9 of the 12 patients toxicity occurred within 60 days of SCT. Major causes of cardiac toxicity were CHF in 6 patients (7%) and atrial fibrillation in 5 patients (6%). Two patients had both CHF and AF. There were no documented episodes of acute myocardial ischemia. Median time to develop a cardiac event was 23 days from SCT (range, 9–200 days). Cumulative incidence of NRM at 100 days was 15% (95% CI 9–24). Only 1 death was directly attributable to a cardiac cause. These results are comparable to SCT performed in patients with normal LVEF. On univariate analysis age > 60 years at the time of SCT and history of smoking were significant predictors for development of cardiac toxicity after SCT. Prior history of smoking remained significant on multivariate analysis (HR 5.7, 95% CI 1.2–29, P=0.03). LVEF, type of transplant or the underlying disease did not emerge as significant predictors of post-transplant cardiac toxicity or NRM. Median survival was worse in patients who developed cardiac complications after SCT (median survival 108 days versus 889 days respectively). CONCLUSIONS: Both allogeneic and autologous SCT are feasible in patients with hematologic malignancies and low LVEF. A prospective study with stratification for cardiac risk factors is warranted in patients with low LVEF.