Single institution experience of posterior reversible encephalopathy syndrome (PRES) associated with high risk pediatric ALL induction therapy: Is there a role of pharmaco-ethnicity.

Abstract

e22005 Background: PRES, a rare complication of childhood leukemia treatment occurs in up to 5% patients in small series and < 1% of patients on the current COG high risk leukemia protocol. Hypertension, chemotherapy and cortical spreading depression have been implicated in the pathophysiology. It is important to recognize the characteristic radiologic findings, manage appropriately and reintroduce chemotherapy since delays can be unfavorable for high risk ALL patients. Pharmaco-ethnicity may determine variation in drug responsiveness and neurotoxicity in children with ALL. Ethnic Differences in occurrence of PRES in pediatric ALL have not been reported. Methods: 12 children (1-20 yrs) diagnosed with ALL between 2011-2016 were retrospectively reviewed for the occurrence of PRES, demographics, chemo-therapy received, clinical features, radiology and management. All literature on PRES in pediatric leukemia on Pubmed was reviewed. Results: 5/12 (42%) children (avg 8.5 yrs) developed PRES during days 10-29 of induction. 80% of the patients that developed and 45% of those that did not develop PRES were Hispanic. All the patients that developed and 3/7 that did not develop PRES were high risk ALL. All patients received vincristine, 4/5 daunorubicin and intrathecal methotrexate and 1/5 peg asparaginase in the 1 week before the event. MRI findings confirmed the diagnosis of PRES in all patients. All patients were in remission based on MRD and spinal fluid cytology. 3/5 patients had clinical and electroencephalographic seizures and hypertension at the time of the event. All patients had complete neurologic recovery. Conclusions: Hispanic ethnicity, high risk ALL and exposure to vincristine ,daunomycin and intrathecal methotrexate during induction were associated with PRES in our cohort . Ethnicity emerged as a new association possibly contributing to the increased incidence of PRES in our cohort compared to historical cohorts. Larger studies to understand the importance of pharmcoethnicity in PRES will help in individualization of chemotherapy with the goal of improving the tolerability and effectiveness of chemotherapy.