No abstract

Since its original description 2 decades ago, posterior reversible encephalopathy syndrome has been reported in children with several predisposing conditions. Epidemiologic data of posterior reversible encephalopathy syndrome in children with hematologic malignancies is still scarce. Herein, we describe the clinical and radiologic features along with the outcome and follow-up of posterior reversible encephalopathy syndrome complicating the treatment of children with hematologic malignancies. Ten patients with a median age of 6.3 years were diagnosed with posterior reversible encephalopathy syndrome. Six of them were undergoing chemotherapy and the remaining 4 were at 37, 52, 78, and 857 days after allogenic hematopoietic stem cell transplant. The median follow-up was 27.6 months. Even though follow-up imaging showed complete resolution of abnormalities in those 10 children, 2 developed secondary epilepsy. Despite accurate diagnosis of posterior reversible encephalopathy syndrome and immediate intervention, neurologic sequelae may still develop. Thus, a close follow-up should be considered in all patients.

The Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant disease caused by TP53 germline mutations. This study aimed to characterize the TP53 mutational spectrum in patients suspected to have LFS in Portugal and to evaluate the influence of the MDM2-SNP309 and TP53-72Arg variants and of telomere length on age of tumor onset. Probands were primarily selected using the classical LFS criteria (two cases) or the more sensitive Chompret Li-Fraumeni-like (LFL) criteria (13 cases), but 12 additional patients that did not comply with those LFS or LFL criteria were included in the analysis based on clinical suspicion (LFS suspects). Nine of the 27 probands (33.3%) presented germline TP53 mutations, two of them occurring de novo and two of them being novel. Three of the nine TP53 mutations were found in families that did not comply with any of the commonly used criteria for TP53 testing, leaving room to recommend the use of less stringent criteria. An association was found between the presence of the TP53-72Arg (but not the MDM2-SNP309) variant and earlier age of onset in TP53 carriers. A negative correlation between telomere length and age of cancer onset was found in patients with germline TP53 mutation, whereas no such correlation was found in controls or in patients with wild-type TP53.

Chromosomal rearrangements affecting the MLL gene are associated with high‐risk pediatric, adult and therapy‐associated acute leukemia. In this study, conventional cytogenetic, fluorescence in situ hybridization, and molecular genetic studies were used to characterize the type and frequency of MLL rearrangements in a consecutive series of 45 Portuguese patients with MLL‐related leukemia treated in a single institution between 1998 and 2011. In the group of patients with acute lymphoblastic leukemia and an identified MLL fusion partner, 47% showed the presence of an MLL–AFF1 fusion, as a result of a t(4;11). In the remaining cases, a MLL–MLLT3 (27%), a MLL–MLLT1 (20%), or MLL–MLLT4 (7%) rearrangement was found. The most frequent rearrangement found in patients with acute myeloid leukemia was the MLL–MLLT3 fusion (42%), followed by MLL–MLLT10 (23%), MLL–MLLT1 (8%), MLL–ELL (8%), MLL–MLLT4 (4%), and MLL–MLLT11 (4%). In three patients, fusions involving MLL and a septin family gene (SEPT2, SEPT6, and SEPT9), were identified. The most frequently identified chromosomal rearrangements were reciprocal translocations, but insertions and deletions, some cryptic, were also observed. In our series, patients with MLL rearrangements were shown to have a poor prognosis, regardless of leukemia subtype. Interestingly, children with 1 year or less showed a statistically significant better overall survival when compared with both older children and adults. The use of a combined strategy in the initial genetic evaluation of acute leukemia patients allowed us to characterize the pattern of MLL rearrangements in our institution, including our previous discovery of two novel MLL fusion partners, the SEPT2 and CT45A2 genes, and a very rare MLL–MLLT4 fusion variant.