ABSTRACT
INTRODUCTION: The objective of the current study was to determine the survival probabilities of children and adolescents with acute lymphocytic leukemia treated with adapted Berlin-Frankfurt-Münster (BFM) protocols and compare our results with the original BFM reports. METHODS: This retrospective study included 695 patients up to 19 years old treated with adapted BFM protocols between 1997 and 2018 in four hospitals in Rio de Janeiro. The 1997-2007 and 2008-2018 cohorts were analyzed separately. RESULTS: More than half of the patients were stratified into the high-risk BFM classification. Overall and event-free survivals were, in the 1997-2007 period, respectively, 88% and 80% (BFM standard risk group-SRG), 75% and 67% (intermediate risk group-IRG), and 48% and 33% (high-risk group-HRG). The corresponding numbers for the 2008-2018 period were 93% and 84% (SRG), 75% and 63% (IRG), and 64% and 57% (HRG). In the second period, both the OS (HR = 0.71, p = 0.011) and EFS (HR = 0.62, p < 0.001) were higher. Except for the intermediate-risk group, the latter results are comparable to the BFM. CONCLUSION: The BFM protocol adaptations can be safely implemented in developing countries, accounting for local specificities.
Subject(s)
Ataxia Telangiectasia/diagnosis , Burkitt Lymphoma/diagnosis , Proto-Oncogene Proteins c-myc/metabolism , Ataxia Telangiectasia/complications , Ataxia Telangiectasia/genetics , Burkitt Lymphoma/complications , Burkitt Lymphoma/genetics , Child , Chromosomes, Human, Pair 8 , Humans , In Situ Hybridization, Fluorescence , Karyotype , Male , Proto-Oncogene Proteins c-myc/genetics , Translocation, Genetic , TrisomyABSTRACT
Myelodysplastic syndromes (MDS) are myeloid malignancies characterized by ineffective hematopoiesis, dysplasia, peripheral cytopenia and increased risk of progression to acute myeloid leukemia. Refractory cytopenia of childhood (RCC) is the most common subtype of pediatric MDS and has overlapping clinical features with viral infections and autoimmune disorders. Mutations in TET2 gene are found in about 20-25% of adult MDS and are associated with a decrease in 5-hydroxymethylcytosine (5-hmC) content. TET2 deregulation and its malignant potential were reported in adult but not in pediatric MDS. We evaluated the gene expression and the presence of mutations in TET2 gene in 19 patients with RCC. TET2 expression level was correlated with 5-hmC amount in DNA and possible regulatory epigenetic mechanisms. One out of 19 pediatric patients with RCC was a carrier of a TET2 mutation. TET2 expression and 5-hmC levels were decreased in patients when compared to a disease-free group. Lower expression was not associated to the presence of mutation or with the status of promoter methylation, but a significant correlation with microRNA-22 expression was found. These findings suggested that TET2 downregulation and low levels of 5-hmC are inversely related to miR-22 expression. The existence of a regulatory loop between microRNA-22 and TET2 may play a role in MDS pathogenesis.
Subject(s)
Cytosine/analogs & derivatives , DNA-Binding Proteins/biosynthesis , Gene Expression Regulation/genetics , MicroRNAs/genetics , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/metabolism , Proto-Oncogene Proteins/biosynthesis , 5-Methylcytosine/analogs & derivatives , Adolescent , Case-Control Studies , Child , Child, Preschool , Cytosine/biosynthesis , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Dioxygenases , Female , High-Throughput Nucleotide Sequencing , Humans , Infant , Male , Mutation , Polymerase Chain Reaction , Proto-Oncogene Proteins/genetics , TranscriptomeABSTRACT
Infants diagnosed with acute myelogenous leukemia (AML) are likely to have subtypes M4 or M5 characterized by 11q23 abnormalities like a t(9;11)(p22;q23). Detection of all possible types of chromosomal abnormalities, including mixed lineage leukemia (MLL) gene rearrangements at 11q23, is of importance for the identification of biological subgroups, which might differ in drug resistance and/or clinical outcome. Here, we report the clinical, conventional banding and molecular cytogenetics data of a 6-month-old boy with an AML-M5 presenting with a unique cryptic rearrangement involving the MLL gene: a three-way t(9;19;11)(p11.2;p13.1;q23).