Journal of Pediatric Hematology/Oncology最新文献

Dengue infection should be considered in the differential diagnosis of febrile neutropenia in endemic areas, even in the absence of warning signs. A retrospective audit was done on medical records of patients (age 14 y or younger) who were diagnosed with dengue fever from April 1, 2023 to March 31, 2024 in a tertiary care cancer center. Patients fulfilling the WHO 2009 criteria of dengue fever and confirmation with detection of either IgM or NS1 were included. Data regarding symptomatology, clinical course, laboratory values, and outcome were analyzed. Twenty-three patients were diagnosed with dengue. Primary malignancy was mainly B-ALL (n=16; 69%). Thirteen patients (56.6%) had criteria fulfilling dengue without warning signs, 5 (21.7%) had dengue with warning signs, and 5 (21.7%) had severe dengue. All patients were treated as inpatients with intravenous fluids and supportive care. Five patients (21.7%) with shock required IVF at 10 mL/kg/h. Two patients (8%) had blood culture positivity and were managed based on the susceptibility pattern. Median delay in chemotherapy was 6 days. The mean duration of hospital stay was 7 days. Three patients (13%) had features of HLH. One patient succumbed to multiorgan failure (with HLH and MDR Klebsiella sepsis).

Background: Timely diagnosis is considered critical in pediatric oncology to optimize treatment outcomes, as delays may impact tumor extension and prognosis. We aimed to assess whether the time to diagnosis and treatment initiation for pediatric patients with rhabdomyosarcoma (RMS) improved over time in Italy and whether longer delays were associated with tumor extension and prognosis.

Methods: We analyzed 749 pediatric patients diagnosed with RMS between 1996 and 2016. Diagnostic interval (DI) was defined as the number of days from symptom onset to diagnosis, while treatment interval (TI) was defined as the time from symptom onset to treatment initiation. DI was correlated with tumor characteristics at diagnosis, and TI was analyzed in relation to survival, using Kaplan-Meier analysis.

Results: The median DI was 32 days, showing a decreasing trend from 39.5 days in 1996 to 2000 to 30 days in 2011 to 2016. A longer DI was associated with age, unfavorable histology, and metastatic disease in univariate analysis, but these were not confirmed in multivariate analysis. The median TI was 48 days. Five-year event-free survival (EFS) and overall survival (OS) were 59.7% and 69.3%. In multivariate analysis, prognosis was negatively associated with age at diagnosis, unfavorable site, nodal involvement, and metastatic disease. TI was not associated with survival.

Conclusions: In our national cohort, the time from symptom onset to diagnosis showed a trend toward shortening in recent years. While a timely diagnosis can provide clarity on the child's condition and potentially reduce parental anxiety, it does not substantially impact tumor characteristics or patient outcomes.

Spindle cell/sclerosing rhabdomyosarcoma (ssRMS) with FUS-TFCP2 translocation is a rare, aggressive RMS subtype often involving facial and pelvic bones and showing poor response to standard therapy. The FUS-TFCP2 fusion drives ALK gene activation and overexpression, suggesting ALK as a therapeutic target, though clinical use of ALK inhibitors remains limited in this context. We report a case of mandibular ssRMS with FUS-TFCP2 fusion treated with the third-generation ALK inhibitor Lorlatinib, resulting in a marked clinical response. We also review the potential utility of ALK-targeted therapies in managing FUS-TFCP2 fusion-positive ssRMS and support further exploration of ALK inhibition in this subset.

Hepatocellular carcinoma (HCC) is a rare malignancy in children, typically requiring chemotherapy, surgical resection, and/or transplant for treatment. Whether HCC arises as a novel tumor (de novo) or in the setting of chronic liver disease determines treatment strategy. We describe a case of a pediatric patient with unresectable HCC due to macrovascular invasion and tumor thrombus of the portal vein who received transarterial radioembolization (TARE) and underwent successful orthotopic liver transplantation outside of Milan criteria.

Hereditary hemochromatosis (HH) is an iron storage disorder characterized by increased iron absorption leading to elevated erythrocyte parameters, including red blood cell (RBC) count. It is the most common genetic disorder in Caucasians and is prevalent in populations with beta-thalassemia. In this study, we retrospectively analyzed the hematological data of 31 pediatric patients with molecularly confirmed HH who were mostly initially suspected of having beta-thalassemia trait (B-TT) due to erythrocytosis. In addition to erythrocytosis, we observed higher-than-expected hemoglobin (Hb) levels for age in these patients. Regardless of low MCV and normal RDW, elevated Hb levels in all patients distinguished them from B-TT cases. Their iron status was normal. These findings suggest that in patients with erythrocytosis and elevated Hb levels, despite other erythrocyte parameters suggestive of B-TT, the possibility of HH should be considered. Since iron overload has not yet developed in pediatric cases, understanding erythrocyte changes is essential for both differential diagnosis and thalassemia eradication.

Purpose: Given trade-offs between whole-body MRI(WBMRI) techniques' attributes for cancer predisposition syndromes (CPS) surveillance, we determined the strength of preferences of adolescents with no cancer history (group 1) and their parents (group 2) (proxies) for different WBMRI surveillance approaches in CPS.

Methods: A proxy cohort of adolescents without cancer history (group 1) and their parents (group 2) completed a discrete choice experiment (DCE) survey on hypothetical situations of cancer surveillance imaging as if they or their children had a CPS. Five attributes (diagnostic accuracy; examination length; radiation exposure; intravenous access discomfort; and contrast extravasation risk) and 3 WBMRI techniques (inversion recovery [IR]; diffusion-weighted [DW]+IR; positron-emission tomography [PET]-MRI) were assessed in association with respondents' age, sex, education level, and prior MRI history.

Results: There were 86 of 342 (25.1%) participants; N=71 (83%) females; 21 (24%) adolescents 12 years or older and 18 years or younger, and 65 (76%) parents. Diagnostic accuracy was ranked highest for importance for groups 1 (47.6%) and 2 (55.3%). Group 1 ranked examination length and risk of radiation exposure as second (23.8%) and third (19.0%) preferred attributes, respectively; group 2 ranked these attributes reversely (15.3% and 18.4%). Group 1 ranked intravenous access discomfort and radionuclide extravasation risk as the fourth preferred attribute, 4.8% each, while they were ranked fourth (7.7%) and fifth (3.7%) for group 2. No agreement was reached for aggregated responses (kappa coefficient=0 or McNemar test P >0.05), or any predictors(multinomial logistic regression) between groups 1 and 2.

Conclusion: Although both adolescents and parents agreed on diagnostic accuracy as the most important attribute in CPS imaging surveillance, other preferences were discordant, opening up discussions about whom the clinical decision-making process should align with.

Background: The KMT2A rearrangements is primarily caused by balanced translocations, with only a very small fraction resulting from deletions or inversions within the long arm of chromosome 11.

Observations: We present a rare case of KMT2A::NRIP3 fusion-positive B-ALL identified through whole transcriptome sequencing (WTS) resulting from pericentric inversion of chromosome 11. Whole-genome sequencing (WGS) analysis revealed that the breakpoints of the KMT2A::NRIP3 fusion were located deep within intron 8 of KMT2A and intron 1 of NRIP3 , accompanied by a pathogenic hotspot mutation (p.Pro74Leu) in the MYC gene. In addition, we found that NRIP3 may negatively regulate Cyclin D1 ( CCND1 ) in acute myeloid leukemia (AML) but not in B-ALL patients.

Conclusions: The rare KMT2A::NRIP3 fusion gene can be observed not only in pediatric AML patients, but also in B-ALL patients.

Unsupervised machine learning shows significant promise for evaluating multicolor flow cytometry, particularly in advancing minimal residual disease (MRD) analysis. We implemented t-distributed stochastic neighbor embedding (t-SNE)-assisted MRD analysis in a challenging case of Philadelphia chromosome-positive acute lymphoblastic leukemia. This approach enabled us to identify MRD on an unbiased basis with a sensitivity comparable to that of genetic analysis while simultaneously reducing the workload. t-SNE is a valuable tool for the detection and verification of MRD, with its effectiveness significantly enhanced through the integration of optimized antibody panels, data preprocessing, and rigorous back-gating verification.

Risk-stratified management with reduced-treatment intensity for standard-risk (SR) patients is an effective strategy. With treatment-related mortality (TRM) continuing to be a major concern in low-middle-income countries, it is vital to limit treatment for patients with favorable disease. We report analysis of 410 consecutive ALL patients from our center treated employing a risk-stratified, response-adapted algorithm. At a median of 8 years from diagnosis, 5-year OS and EFS for the entire cohort and SR group are 84.1%, 81.9%, 91.6%, and 88.5%, respectively. The induction TRM was 1.7% (none in the SR group) reaffirming its efficacy in our setting with relatively limited resources.