Decreased induction morbidity and mortality following modification to induction therapy in infants with acute lymphoblastic leukemia enrolled on AALL0631: a report from the Children's Oncology Group.

BACKGROUND: Infants with acute lymphoblastic leukemia (ALL) have a poor prognosis. Intensification of therapy has resulted in fewer relapses but increased early deaths, resulting in failure to improve survival. PROCEDURE: AALL0631 is a Phase 3 study for infants (<366 days of age) with newly diagnosed ALL. Induction initially (Cohort 1) consisted of 3 weeks of therapy based on COG P9407. Due to excessive early mortality, induction was amended to a less intensive 5 weeks of therapy based on Interfant-99. Additionally, enhanced supportive care guidelines were incorporated with hospitalization during induction until evidence of marrow recovery and recommendations for prevention/treatment of infections (Cohort 2). RESULTS: Induction mortality was significantly lower for patients in Cohort 2 (2/123, 1.6%) versus Cohort 1 (4/26, 15.4%; P = 0.009). All induction deaths were infection related except one due to progressive disease (Cohort 2). Sterile site infections were lower for patients in Cohort 2 (24/123, 19.5%) versus Cohort 1 (15/26, 57.7%; P = 0.0002), with a significantly lower rate of Gram positive infections during induction for patients in Cohort 2, P = 0.0002. No clinically significant differences in grades 3-5 non-infectious toxicities were observed between the two cohorts. Higher complete response rates were observed at end induction intensification for Cohort 2 (week 9, 94/100, 94%) versus Cohort 1 (week 7, 17/25, 68%; P = 0.0.0012). CONCLUSION: De-intensification of induction therapy and enhanced supportive care guidelines significantly decreased induction mortality and sterile site infections, without decreasing complete remission rates.

Severely blunted early heart rate response during treadmill exercise is associated with above average exercise capacity.

INTRODUCTION: Chronotropic response with exercise is evaluated by peak heart rate (HR) achieved. Since most of the exercise-related chronotropic response occurs early after exercise is initiated, we investigated whether the HR achieved with a standard dose of exercise (Bruce stage 2) is associated with exercise capacity. We hypothesized that those with a blunted or disproportionate HR response at this exercise dose would have reduced exercise capacity compared to those with a typical HR response. MATERIAL AND METHODS: We reviewed 3,084 consecutive normal maximal treadmill stress echocardiographic reports acquired from individual adults over a 1.5-year period. We examined for association between stage 2 Bruce HR with age and sex-adjusted exercise capacity. RESULTS: After adjustment for age and sex, Bruce stage 2 HR was inversely associated (ß = -0.08, p < 0.01) with exercise duration. Thus for every additional 10 beats per minute achieved in stage 2, exercise duration was generally shortened by about 45 s. Most of the subjects (92%) who had a stage 2 Bruce HR response below the 10th percentile had above average or average exercise capacity for their age and sex. CONCLUSIONS: Lower Bruce stage 2 HR was associated with increased exercise capacity. Severely blunted HR response was associated with above average exercise capacity. Caution should therefore be exercised in attributing exercise intolerance to a blunted HR response when making a diagnosis of chronotropic incompetence.

Alemtuzumab induced ST-segment elevation and acute myocardial dysfunction.

Cardiac toxicity as a side effect of chemotherapeutic agents has been well reported in the literature. Cardiac toxicity secondary to alemtuzumab has been reported, presenting as congestive heart failure and arrhythmias. Here we report a case of acute myocardial dysfunction after administration of a test dose of alemtuzumab. Our patient was a 66-year-old man with a history of small lymphocytic lymphoma/chronic lymphocytic lymphoma who received a test dose of alemtuzumab. Twenty minutes post administration, the patient developed nausea, vomiting, rigors, and tachycardia. Electrocardiography (ECG) showed acute ST-segment elevations in contiguous leads V2-V6, I, and AVL with no associated chest pain. Bedside echocardiogram showed akinesis of the anterior septum, apex, distal anterior wall, and decreased left ventricular ejection fraction. Cardiac catheterization showed non-critical occlusive disease and no intervention was undertaken. Post-catheterization ECG revealed resolution of ST segment elevations, TWI in V4-V6, and prolongation of corrected QT. Repeat echocardiogram 10 days after the event demonstrated no improvement in wall motion or ejection fraction. We discuss the possible mechanisms causing ST-elevations and acute myocardial dysfunction after treatment with alemtuzumab. .