Assessment of endocrinologic and cardiologic late effects among survivors of childhood leukemia

Objectives: Survival rates for childhood acute leukemia have significantly improved and late effects of therapy have been described in leukemia survivors. Growth failure, obesity, cardiac toxicity, hypertension, dyslipidemia, insulin resistance, thyroid gland disorders such as hypothyroidism, pubertal disorders, infertility, osteopenia/osteoporosis, avascular necrosis of the bone, neurocognitive dysfunctions and second neoplasms are reported as late effects. Childhood leukemia survivors should be followed up for long term late effects. The objective of this study is to identify the endocrinologic and cardiologic late effects of acute leukemia patients.Materials and Methods: Patients treated for leukemia with BFM protocols in Dokuz Eylül University Department of Pediatric Hematology after at least five years of diagnosis were included in the study. Demographic features, endocrinologic late effecs (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders such as hypothyroidism, osteopenia/osteoporosis, pubertal disorders) and cardiologic late effects (cardiac toxicity, hypertension) were evaluated cross sectionally in these patients. The study group was evaluated with anthropometric measurements, body mass index, laboratory testing of fasting glucose, insulin, serum lipids and thyroid functions. Pubertal stage was determined by using the Tanner criteria. Bone mineral densities were measured by DEXA (dual-energy X-ray absorptiometry). Blood pressures were noted. Evaluation of cardiac systolic and diastolic functions were performed using standard M-mode echocardiyography and tissue doppler imaging. Statistical data were evaluated by SPSS 15.0 software. Chi-square and Mann-Whitney U tests were used. P<0.05 was selected as the value reflecting the statistical significance.Results: Of 43 acute leukemia survivors with a median age of 15 (range; 7-30 years), 23 (54%) were females and 20 (46%) were males. Five (12%) of the patients had acute myeloid leukemia and 38 (88%) of them had acute lymphoblastic leukemia. They had been off therapy for an average of eight years (range; 5-17 years, SD 3.4 years). At least one adverse event occured in 25 (58%) of the 43 survivors, with 10 of them (23%) having multiple problems. Six (14%) of the survivors were obese and 10 (23%) of them were overweight. Subjects who were overweigth or obese at the time of diagnosis and at the end of therapy were more likely to be obese at last follow-up. Obesity was more frequently determined in patients who were younger than six years of age at the the time of diagnosis. Insulin resistance was observed in nine (21%) subjects. Insulin resistance was more frequently seen in subjects who are overweight or obese and who have family history of type 2 DM. Hyperlipidemia was detected in eight (19%) of the 43 survivors. Premature telarche was detected in one (2%) subject. None of the patients had short stature. Hypothyroidism was observed in one (2%) survivor. Two (5%) survivors had osteopenia. Avascular necrosis of femur head occurred in two (5%) survivors and one of them had arthroplasty. Cardiovascular abnormalities occurred in one (2%) of the subjects with hypertension and cardiac diastolic dysfunction. No statistically significant difference was determined for the distribution of late effects between subjects who received cranial radiotherapy or not.Conclusion: In our study at least one adverse event occured in most of the cases. Obesity was more frequently seen in patients who were overweight or obese before therapy and who were younger than six years of age at the time of diagnosis. Patients who were overweigtht or obese and who had a family history were more likely to have insulin resistance. The lower frequency of other endocrinologic late effects might be related to the low dose of cranial radiotherapy (? 18 Gy). It is determined that cardiotoxic effects may occur in a few cases. Acute leukemia survivors should be followed up for the endocrinologic and cardiologic late effects with concerning sex and age at diagnosis, contents of the therapy such as antracycline dose, radiotherapy dose and radiotherapy region.