Ana Luiza de Melo Rodrigues

Acute myeloid leukemia (AML) during pregnancy is rare and requires urgent maternal treatment while fetal toxicity and prematurity must also be considered. We report a 17-year-old adolescent diagnosed with AML at 21 weeks and 6 days of gestation, based on first-trimester ultrasonographic dating, after presenting with severe pancytopenia, pneumonia, COVID-19, and septic shock. Bone marrow evaluation showed 73.3% blasts, with an immature myeloid immunophenotype; conventional cytogenetics showed 46,XX[20]. Available molecular testing was negative for CBFB::MYH11, FLT3-ITD, and NPM1, but broader molecular profiling was not available. Based on the studies available, the leukemia was most consistent with AML defined by differentiation under WHO 2022 and AML, not otherwise specified under ICC 2022, while acknowledging that incomplete molecular testing precluded definitive exclusion of genetically defined AML entities. After multidisciplinary counseling, the patient chose to continue the pregnancy. Because of recent septic shock, ongoing pregnancy, and concern for toxicity from intensive induction, treatment was initiated with the low-dose MAG regimen used in the Brazilian pediatric GELMAI protocol (mitoxantrone, low-dose cytarabine, and G-CSF). After MAG I, bone marrow evaluation showed no morphologic evidence of residual leukemia and no measurable leukemic population by multiparameter flow cytometry at the reported assay sensitivity; subsequent peripheral blood count recovery was documented, consistent with complete remission (CR). Cesarean delivery was required at 28 weeks and 5 days of gestation because of fetal growth restriction. The patient subsequently completed protocol-directed therapy and remained without evidence of relapse at last follow-up. The child survived very preterm birth and, at follow-up in April 2026, had growth parameters near the 50th percentile, age-appropriate neurodevelopment, a normal complete blood count, and a normal echocardiogram. This case illustrates a carefully selected, non-standard low-dose bridge strategy when immediate intensive induction was considered particularly hazardous; it does not establish generalizable efficacy or long-term fetal safety.

The TP53 R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 cohort with 4165 R337H carriers living in Paraná state (PR) subregions. The effectiveness of a second surveillance for R337H probands selected from 42,438 tested newborns in PR (2016 cohort) was tested to detect early stage I tumor among educated families without periodical exams. Estimation of R337H frequencies and ACT incidence in Santa Catarina state (SC) used data from 50,115 tested newborns without surveillance, ACT cases from a SC hospital, and a public cancer registry. R337H carrier frequencies in the population were 0.245% (SC) and 0.306% (PR), and 87% and 95% in ACTs, respectively. The ACT incidence was calculated as ~6.4/million children younger than 10 years per year in PR (95% CI: 5.28; 7.65) and 4.15/million in SC (CI 95%: 2.95; 5.67). The ACT penetrance in PR for probands followed from birth to 12 years was 3.9%. R337H carriers living in an agricultural subregion (C1) had a lower risk of developing pediatric ACT than those living in industrial and large urban subregion (relative risk = 2.4). One small ACT (21g) without recurrence (1/112) was detected by the parents in the 2016 cohort. ACT incidence follows R337H frequency in each population, but remarkably environmental factors modify these rates.

Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8⁺) cytotoxic T lymphocytes (CD8⁺-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8⁺-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8⁺-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8⁺ T cell recognition may provide insights for future pre-clinical studies.