RESUMEN
This retrospective correlation study investigated the putative link between methylene tetrahydrofolate reductase (MTHFR) A1298C mutations and chemotherapy-related brain function changes in adult childhood-leukemia survivors. To this end, we determined the relationship between the particular MTHFR1298 genotype (AA, AC or CC) of 31 adult childhood-leukemia survivors, and (1) their CSF Tau and phosphorylated Tau (pTau) levels at the time of treatment, (2) their adult performance intelligence quotient (PIQ), and (3) their regional brain connectivity using diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (rsfMRI). We confirmed that neuropathology markers Tau and pTau significantly increased in CSF of children after intrathecal methotrexate administration. Highest concentrations of these toxicity markers were found during the induction phase of the therapy. Moreover, CSF concentrations of Tau and pTau during treatment were influenced by the children's particular MTHFR1298 genotype. CSF Tau (but not pTau) levels significantly dropped after folinic acid supplementation. At adult age (on average 13.1 years since the end of their treatment), their particular MTHFR1298 genotype (AA, AC or CC) influenced the changes in PIQ and cortical connectivity that we found to be related to their childhood exposure to chemotherapeutics. In summary, we suggest that homozygous MTHFR1298CC individuals are more vulnerable to the adult sequelae of antifolate chemotherapy.
Asunto(s)
Cognición/efectos de los fármacos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Encéfalo/patología , Supervivientes de Cáncer , Niño , Preescolar , Imagen de Difusión por Resonancia Magnética/métodos , Progresión de la Enfermedad , Quimioterapia/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Femenino , Antagonistas del Ácido Fólico/uso terapéutico , Genotipo , Humanos , Pruebas de Inteligencia , Imagen por Resonancia Magnética/métodos , Masculino , Metotrexato/uso terapéutico , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , Polimorfismo de Nucleótido Simple/genética , Descanso/fisiología , Estudios Retrospectivos , Adulto Joven , Proteínas tau/análisis , Proteínas tau/líquido cefalorraquídeoRESUMEN
PURPOSE: Adolescent and young adult cancer (AYAC) survivors show an elevated risk of distress. Targeted psychosocial interventions for this distinct population are needed. This study examined the potential efficacy of a mindfulness-based intervention (MBI) to alleviate emotional distress and improve quality of life (QoL) in AYAC survivors. METHODS: Participants were 16 AYAC survivors, aged 14-24, who had completed acute medical treatment. A two-baseline (8 and 1 week before the intervention), post- (1 week after the intervention) and 3 months follow-up within-subjects design was used. Each participant completed two baseline assessments, followed by an 8-week MBI. The primary outcome variables were emotional distress and QoL. Secondary outcomes were cognitive vulnerability factors and mindfulness skills. RESULTS: Multilevel modeling showed (1) a significant reduction in emotional distress and improvement in QoL at 3 months of follow-up, (2) a significant reduction in negative attitudes toward self (i.e., a cognitive vulnerability factor), and (3) a significant improvement in mindfulness skills. CONCLUSION: MBI is a promising approach that is used to treat emotional distress and to improve QoL in AYAC survivors. Further research using randomized controlled trials is needed to generalize these findings. Trial registration information: www.trialregister.nl ; NTR4358.