Journal of Pediatric Hematology/Oncology最新文献

Embryonal tumors with multilayered rosettes (ETMR) represent a distinct entity characterized by aggressive behavior. Historical retrospective analyses have documented dire overall survival rates ranging from 0% to 14% at 1 year. However, a contemporary report by Khan and colleagues shows overall survival rates reaching 29% at 2 years and 27% at 4 years. We present the case of an 18-month-old girl diagnosed with ETMR, confirmed by chromosome 19 microRNA cluster amplification following initial presentation with focal seizures. The patient underwent a combination of surgical interventions, high-dose chemotherapy with stem cell rescue, and proton therapy, achieving a disease-free status after completing standard treatment. Subsequently, a 12-month maintenance regimen comprising intrathecal topotecan, oral sodium valproate, and oral cis-retinoic acid was administered. The maintenance therapy was well tolerated, with manageable adverse effects. The patient remains progression-free for 32 months postmaintenance therapy (50 months from initial presentation). This study explores the feasibility and safety profile of maintenance therapy in ETMR. Future studies may explore this approach to determine its efficacy in children with ETMR.

The aim of this study was to identify catheter-related bloodstream infection (CRBSI) episodes, to determine the causative agents and antibiotic susceptibility profiles, demographic characteristics, and clinical outcomes of patients treated in the pediatric bone marrow transplant (BMT) unit between November 2019 and July 2022. Forty patients were included in the study. The median patient age was 7.5 years (range: 1.5 to 19.9 y) and the most common underlying disease was ALL (77.5%). CRBSI was found to be significantly higher in haploidentic donors (P<0.001). When CRBSI was confirmed, 65% of the patients were neutropenic with a median duration of 17.5 days (range: 3 to 150). It was found that the mean time to CVC infection was 22 days (range: 5 to 118). As a result of multivariate logistic analysis (OR: 1.038 [95% CI: 1.007-1.070], P=0.018) of the time of infection of the catheter and mortality, it was determined that the mortality rate increased as the duration of the catheter remained. CRBSI was detected in 41.2% of transplanted patients and the overall mortality rate attributed to this complication was 10%. Among the patients, 22 (55%) were colonized before hematopoietic stem cell transplantation (HSCT), and gram-negative agents (n=15, 68%) mostly accounted for colonization. Gram-negative pathogens (60%) were found to be statistically significantly more common in CRBSI (P<0.01). The most common causative agent was K. pneumoniae (n=13, 32.5%). Of the gram-negative isolates (n=24), 17 (70.8%) were multidrug-resistant organisms (MDRO). A fluoroquinolone (80%) was used for antibiotic prophylaxis. Among patients with CRBSI, 65% had a fluoroquinolone-resistant isolate. We found a high rate of quinolone resistance among CRBSI isolates after the use of fluoroquinolone prophylaxis at our unit.

Childhood acute lymphoblastic leukemia survivors (ALL-S) face an increased risk of abnormal glucose metabolism (AGM). This study aimed to assess glucose metabolism in 141 ALL-S. All underwent an oral glucose tolerance test (OGTT) and were classified into AGM and normal glucose tolerance (NGT) groups. Insulin sensitivity and secretion indices were calculated from plasma glucose and serum insulin derived from the OGTT. Fat mass index (FMI) was derived from body composition analysis. Sixty-seven of 141 (48%) ALL-S had AGM. AGM was demonstrated in 33 of 98 nonobese ALL-S. ALL-S with AGM had a greater waist circumference percentile and FMI SD score than those with NGT. In addition, ALL-S with AGM had lower insulin sensitivity (greater homeostasis model assessment of insulin resistance: 2.3 [1.4, 3.3] vs. 1.0 [0.5, 1.4], P <0.001 and lower whole-body insulin sensitivity index: 3.5 [2.3, 4.1] vs. 7.9 [5.3, 10.9], P <0.001) and lower insulin secretion relative to insulin sensitivity (disposition index: 5.8 [4.2, 10.2] vs. 10.0 [6.1, 14.6], P <0.001) than those with NGT. Therefore, ALL-S could develop AGM regardless of their body mass index status. AGM in ALL-S stemmed from both insulin resistance and impaired insulin secretion.

Atypical teratoid/rhabdoid tumors (AT/RT) are malignant central nervous system (CNS) tumors. Typically, AT/RT is classified as SMARCB1 (INI-1) deficient or as SMARCA4 (BRG1) deficient. In this case, we describe a unique case of AT/RT with a novel SMARCA4 missense variant identified on next-generation sequencing but retained expression of INI-1 and BRG-1 on immunohistochemistry. Diagnosis of the tumor and discovery of the novel SMARCA4 variant was only possible after comprehensive tumor molecular testing tailored for pediatric malignancies. This case highlights the importance of molecular genetic testing as part of a workup in neoplasms concerning for possible AT/RT.

Alectinib, an ALK inhibitor used for ALK+ non-small cell lung cancer and other malignancies, has been associated with anemia and RBC abnormalities, including acanthocytosis. We report the first case of alectinib-induced acanthocytosis and hemolysis causing anemia during treatment for anaplastic large cell lymphoma in an 11-year-old boy. Extensive testing, including next-generation sequencing, and a specific indirect antiglobulin test conducted with alectinib, was performed to document this hemolytic anemia. Dose reduction improved hemoglobin levels, allowing completion of the 2-year treatment, suggesting a dose-dependent mechanism. Blood counts and morphology normalized after discontinuation of alectinib. A comprehensive literature review and discussion of the underlying mechanisms are also provided.

Alterations of PHOX2B function is associated with a wide range of diseases, including congenital central hypoventilation syndrome (CCHS) and neural crest-derived tumors, from low-grade (ganglioneuromas) to malignant forms (neuroblastomas). We report a case bearing a novel nonpolyalanine repeat PHOX2B pathogenic variant presenting both as high-risk neuroblastoma and late-onset CCHS. CCHS was revealed upon severe respiratory decompensation while the patient was administered the anti-GD2 antibody dinutuximab-beta, as part of neuroblastoma treatment. From this experience, we make propositions for the management of patients with high-risk neuroblastoma and a constitutional pathogenic variant of PHOX2B .

In the literature, long-term autoinflammatory disease (AID)-like symptoms are extremely rare in childhood acute leukemia cases. Here, we report a 14-month-old girl with KMT2A::LASP1 -positive acute monocytic leukemia diagnosed after a 7-month course of AID-like symptoms. KMT2A::LASP1 fusion was retrospectively detected in her bone marrow at the initial presentation of AID-like symptoms, suggesting the involvement of leukemia cells in her AID-like symptoms. Immediately after starting chemotherapy, the patient sequentially developed leukemic cell lysis pneumopathy (LCLP), which was successfully overcome by the continuation of chemotherapy under intensive respiratory support, thus suggesting a possible association of her AID-like symptoms with the development of LCLP.