Posterior Reversible Encephalopathy Syndrome: Risk Factors and Impact on the Outcome in Children With Acute Lymphoblastic Leukemia Treated With Nordic Protocols

Abstract

Posterior reversible encephalopathy syndrome (PRES) in children with acute lymphoblastic leukemia has been increasingly recognized as a clinicoradiological entity. Our aim was to describe the incidence of PRES in pediatric patients with ALL, identify its risk factors, and examine its prognostic importance. For this research, we conducted a systematic, retrospective review of the patient records in a population-based series of children with acute lymphoblastic leukemia (n=643) treated in Finland from 1992 to 2008. Of the patients with ALL, 4.5% (n=29) developed radiologically confirmed PRES, of which 28 cases occurred during induction. Hypertension (P=0.006; odds ratio [OR], 4.10, confidence interval [CI], 1.50-11.25), constipation (P=0.001; OR, 5.60; CI, 2.02-15.52), and >14 days of alkalinization (P=0.017; OR, 3.27; CI, 1.23-8.68) were significant independent risk factors for PRES. One-third of the patients developed epilepsy. Relapses occurred significantly more often in those patients with PRES (P=0.001), which was associated with worse overall survival (P=0.040; 5-year survival=75.9% [60.3%-91.4%] vs. 88.4% [85.8%-90.9%]). Using NOPHO-ALL 92/2000 protocols, PRES is a significant early complication of therapy in ALL, and was associated with a poorer prognosis and significant neurological morbidity.

Analysis of Risk Factors Associated With Poor Outcome in Posterior Reversible Encephalopathy Syndrome After Treatment in Children: Systematic Review and Meta-Analysis

“…Additionally, the two new findings suggested that CNS involvement/leukemia was related to a significantly higher risk of PRES as compared with no CNS involvement/ leukemia. Tcell leukemia had a higher risk of PRES in pediatric hematologic disease after conducting chemotherapy (2,20). The study on the risk factors of the incidence between PRES related to T-cell leukemia and CNS leukemia/involvement in our analysis showed that the risk of PRES in children with T-cell leukemia significantly increases.…”

“…Although numerous studies have investigated PRES continuously, the specific risk factors of developing PRES in children remain unclear, since PRES occurs before or during acute neurological symptoms, such as seizures, mental impairment, visual disturbance, headache, vomiting, and other risk factors associated with progressing long-term neurological disorder or death. Of the six studies included (2,8,18,20,25,27), we found that data on sex (male), age group ≥10 years (or 10.0-20.0 years), acute GVHD, hypertension, immunodeficiency, sickle cell disease, T-cell leukemia, CNS leukemia/involvement are associated with poor outcomes or prognoses of patients with PRES and is a limitation on children. In this meta-analysis, a significantly higher incidence of risk was found in female children than in male children in the oncologic age groups of PRES.…”

“…In children, the lower limit of CBF autoregulation is 40 mmHg, but in adults, its average is about 50-60 mmHg; as a result, hypertension is more common in pediatric PRES (43). A series of currently published studies, that ranged from 2015 to 2020, investigating PRES-hypertension in pediatric oncology or hematology diseases suggested that ∼67-100% of PRES patients had hypertension after undergoing HSCT or chemotherapy (2,15,16,18,20,22,24,25,(44)(45)(46). The result of our analysis suggested that hypertension can promote the occurrence of PRES in children.…”

“…Despite several recent studies in which the impact of various risk factors on PRES were investigated, the consensus and position statement on these factors on the prognosis of PRES in childhood cancer have still been based on expert opinion and not empirical evidence (2,8,16,(18)(19)(20)(21)(22)(23)(24)(25)(26). Therefore, we believe that our studies are warranted by a more focused review of the literature.…”

“…After the full-text articles of the remaining 11 studies were reviewed, five studies were excluded (the reasons for exclusion are detailed in Figure 1), and eventually, six reports (because of the lack of full-text article, one editorial was included) were included in this meta-analysis. A total of six studies (2,8,18,20,25,27) were selected for meta-analysis, and due to the lack of full-text articles, one of them was included as an editor study (27). All the reviews were observational cohort studies.…”