Late effects in survivors of childhood acute lymphoblastic leukemia in the context of selected gene polymorphisms

BACKGROUND: It has been shown that approximately half of survivors of childhood acute lymphoblastic leukemia (ALL) have symptomatic late effects (LE) that may be severe or life-threatening. The aim of our study was to assess the health status of childhood ALL survivors after over 10 years of follow-up and to assess its relationships with gene polymorphisms, numbers and types of LEs, as well as with intensity of chemotherapy and cranial radiotherapy (CRT). METHODS: We conducted a telephone survey in 125 ALL survivors (median time from completion of treatment was 12 years) and compared the results with those obtained in our previous study. Most of the patients were followed-up by local providers. RESULTS: The prevalence of LEs of approximately 50% was similar in both study groups. More than one LE was found in almost 25% of patients. Endocrine LEs were less frequent than in our previous study (44% vs 22%), probably due to underdiagnosis. The prevalence of hepatitis B/C decreased from 30%/50 to 18% (counted together), and prevalence of neurologic LEs decreased from 18 to 6%. The increase in the rate of second malignancies was not significant (2% vs. 3%). Sixty four percent of patients continued their education at the time of the study. Approximately 51% of ALL survivors who have completed their education by the time of the study had no permanent employment, including 4 mothers of infants and 3 persons qualified for a disability living allowance. These employment problems may have been due to cognitive impairment. The offspring of the ALL survivors included 11 children, all of them healthy. Further analysis showed higher prevalence of hepatitis in patients treated with CRT (p = 0.0001). Genetic studies revealed higher prevalence of hepatitis in patients homozygous for the rs9939609A variant of the FTO gene compared with other patients (p = 0.03). Moreover, wild-type rs1137101 polymorphism (Q223R) of the and leptin receptor gene was more frequent in patients with psychological LEs (p = 0.03). CONCLUSIONS: The prevalence of LEs in ALL survivors is of key importance. The transition of childhood ALL survivors from pediatric to adult care should be urgently improved to maintain continued follow-up provide high-quality care. TRIAL REGISTRATION: Bioethics Committee of the Jagiellonian University approved the study protocol. Registration number: KBET/113/B/2006.