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Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia: Experience of a single center using BFM protocols

To the Editor: We read with interest the study by Stavroula Anastasopoulou on 1,378 children with acute lymphoblastic leukemia (ALL), treated with NOPHO ALL2008 protocol; the authors diagnosed them with posterior reversible encephalopathy syndrome (PRES) in 52 cases (3.7%). They found that older age, T cell type, central nervous system (CNS) leukemia, and high-risk treatment are risk factors for PRES. Seven patients had epilepsy, seven patients had neurologic problems, and in total 27% had sequela.1 We retrospectively evaluated the charts of 312 patients (1 month–18 years) with ALL treated via the Berlin-Frankfurt-Münster (BFM) protocol between 1995 and 2015. We included 304 patients in our analyses; 74.8% had common B-ALL and 17.7% had T-cell ALL. At the time of diagnosis, 25 (8.3%) had CNS involvement and 23 (7.7%) patients had traumatic lumbar punctures. According to the protocol, 22.7% were in the standard risk group, 59.95% were at medium risk, and 17.4% were in the highrisk group. Cranial radiotherapy was applied to 61.2%. Recurrences were detected in 39 (12.8%) cases. Two patients had CNS recurrences in the first 10 years. Two patients (0.6%) had isolated cranial nerve involvement at the time of diagnosis, and 1 (0.3%) had mass and optic nerve involvement due to ALL involvement. Thirteen patients (4.3%) had reversible posterior leukoencephalopathy (Table 1). The mortality rate of all of the patients was 17.1% (52/304), the 5year event-free survival was 79.9 ± 4.7%, and overall survival was 83.2± 4.1%. PRES is a complication in childhood cancer treatment, mostly leukemia.2–4 Most commonly, parietal and occipital lobes are affected.4,5 Clinical and radiological findings in patients with PRES are usually temporary. However, the neurological damage of PRES may not entirely be reversible in patients with cancer. Treatment includes anticonvulsants, antihypertensives, rehabilitation, and avoidance of triggering agents. Chemotherapy can be safely continued after the resolution of symptoms.5 In retrospective studies, the PRES incidence in children with leukemiawas1.6–3.95%.6 Banerjee et al foundPRES incidence of 4.5% (29/643) in 643 patients treated with Scandinavian protocols.6 We diagnosed 13 (4.3%) patients as PRES, of whom 11 cases were over 6 years old, and only twowere<5 years old. Similar to Kim et al's study,7 PRES occurred during the induction phase of the treatment protocol in 10 of our patients. Most cases were in the medium risk group. PRES recurred in two (15.4%) of our cases. This rate was in accordance with a 10-56% recurrence risk in the literature.8 de Laat et al reported that six of their 56 patients (12%) had persistent neurological sequela, and one died due to status epilepticus.5 Only one of our patients (7.7%) had epilepsy as a sequela. We did not lose any patient after we had diagnosed him or her as PRES. Herein, we emphasize that PRES is a common neurological complication in pediatric ALL treatment, and the patients should be followed carefully for recurrence and sequela. Our experience with BFM protocols was similar to the NOPHO ALL2008 protocol results.