Childhood acute lymphoblastic leukaemia. Late effects in young adult survivors

Abstract

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. The 5-year survival rate has gradually increased from 5% in early 1970s to over 80% today. Until now most patients have been discharged from further follow up after puberty. The general aim of this thesis was to investigate long-term side effects in a homogenous group of young adult survivors of childhood ALL.Thirty-five young adults in the age 20-32 years, who had been treated for ALL before puberty, were investigated. They had all received chemotherapeutic treatment and corticosteroids. Nineteen had received a low dose prophylactic radiotherapy to the central nervous system (18-24 Gy).In spite of little or no effect on final height we found low spontaneous GH secretion during 24-hours in 50% of the cranially irradiated patients. Low serum levels of IGF-I did not identify patients with low GH secretion. One third of the patients were overweight (BMI 25-29.9 kg/m2), but no patient was obese according to WHO criteria (BMI ¡Ý 30 kg/m2). The maximal GH peak correlated to percentage of total body fat, trunk fat and fat free mass. Reduced GH secretion was correlated with unfavourable serum lipid levels. Thirty-seven percent fulfilled one or two criteria for the metabolic syndrome although no patient had the complete syndrome by definition. Bone mineral density (BMD) was slightly reduced in lumbar spine (-0.4 SD). BMD and markers of bone turnover in femoral neck were correlated to physical performance but not to spontaneous GH secretion. Twenty-three patients who all had received anthracyclines in comparably low doses were also investigated with exercise stress echocardiography and compared with 12 healthy controls. The results demonstrated subclinical, left ventricular systolic dysfunction detected at stress, in 50% of the patients. The most marked difference was in ejection fraction at stress; 10 out of 23 patients reduced their ejection fraction at stress compared with at rest; this was not found in any of the controls. Conclusions. In this study with very long follow up in a homogenous cohort of seemingly healthy adult ALL survivors, we found reasons for future follow up. The main findings are risk of GH deficiency in cranially irradiated patients and risk of anthracycline-induced systolic cardiac dysfunction and other metabolic risk factors. Furthermore, we propose that lifestyle education promoting physical activity is encouraged from an early point in time for ALL patients to prevent obesity and impaired bone mineral density.