Long-term neurotoxicity among childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC Children Leukemia Group studies

Abstract

Survival after childhood acute lymphoblastic leukemia (ALL) has increased over the last 40 years with an overall survival above 90%. Survivors may experience neurological late effects secondary to chemotherapy and radiotherapy. This observational retrospective study evaluated the cumulative incidence of neurological late effects among 890 childhood ALL survivors treated in EORTC CLG trials (58741, 58831/2 and 58881) between 1971 and 1998. Median follow-up was 19 years and interquartile range of the follow-up was 15–22 years. At 20 years from the end of treatment, approximately 66% of patients from the 58741 trial (accrual time: 1971–1978) and approximately 15% from the more recent trials had cognitive disturbance grade 1 or higher. Cumulative incidences at 20 years from treatment end of seizures, stroke and leukoencephalopathy were respectively 45%, 16% and 62% in study 58741, 13%, 2% and 5% in study 58831/2, and 8%, 2% and 3% in study 58881. Patients who were 10–17 years of age at diagnosis had a higher incidence of stroke and leukoencephalopathy as compared to those less than 6 years of age. Noteworthy, all neurological late effects continued to occur beyond 5 years after end of treatment. This retrospective study highlights the frequency of neurological late effects in survivors of childhood ALL. With the increase of the overall survival of ALL patients, the role and potential benefit of longitudinal neurological screening should be evaluated in further studies as these neurological late effects become an important public health challenge. This study is part of the larger EORTC CLG 58 Late Adverse Effects (LAE) study (ClinicalTrials.gov Identifier NCT01298388, date of registration February 16, 2011).

Different Levels of Therapeutic Strategies to Recover the Microbiome to Prevent/Delay Acute Lymphoblastic Leukemia (ALL) or Arrest Its Progression in Children

“…The major ALL complication, which can lead to mortality, is the involvement of the central nervous system (CNS), with the development of typical symptoms, including the loss of balance, headache, fainting, nausea, or, more rarely, swallowing difficulties. The severity of such symptomatology depends on leukemic infiltration in CNS and consequently in its entity or increasing presence in CNS areas [6][7][8]. In addition, ALL appears underestimated due to underdiagnoses since it is asymptomatic 2 of 20 in most cases.…”

Different Levels of Therapeutic Strategies to Recover the Microbiome to Prevent/Delay Acute Lymphoblastic Leukemia (ALL) or Arrest Its Progression in Children

“…The major ALL complication, which can lead to mortality, is the involvement of the central nervous system (CNS), with the development of typical symptoms, including the loss of balance, headache, fainting, nausea or, more rarely, swallowing difficulties. The severity of such symptomatology depends on the leukemic infiltration in CNS, and consequently in its entity or better in the amount of CNS areas involved [6][7][8]. In addition, ALL appears underestimated, because underdiagnosed for being asymptomatic in most cases.…”