Pediatric Hematology and Oncology最新文献

Pediatric acute myeloid leukemia (AML) is a heterogeneous and aggressive hematological malignancy. Despite advances in treatment, the survival rates remain unsatisfactory, emphasizing the need for innovative therapeutic approaches. This narrative review presents a comprehensive overview of the current approach and likely future directions for pediatric AML. The distinct genetic, epigenetic, and molecular features of pediatric AML contribute to its complex pathophysiology and impact on prognosis. Current treatment practices involve a multifaceted approach combining chemotherapy, molecularly targeted therapies, and hematopoietic stem cell transplantation. However, intensive treatment often leads to significant acute and long-term toxicity. Emerging strategies, including precision medicine, immunotherapy, and novel agents, hold promise for improving outcomes and minimizing adverse effects. Ongoing clinical trials are investigating the potential of these innovative approaches to transform pediatric AML care. By highlighting the evolving treatment paradigms and future perspectives, this review underscores the importance of continued research and development in pediatric AML to enhance the survival rates and quality of life of these young patients.

Temporal trends demonstrate improved survival for many types of common pediatric cancer. Studies have not examined improvement in very rare pediatric cancers or compared these improvements to more common cancers. In this cohort study of the Surveillance, Epidemiology, and End Results (SEER) registry, we examined patients from 1975 to 2016 who were 0-19 years of age at the time of diagnosis. Cancers were grouped by decade of diagnosis and 3 cancer frequency groups: Common, Intermediate, and Rare. Trends in mortality across decades and by cancer frequency were compared using Kaplan-Meier curves and adjusted Cox proportional hazards models. A total of 50,222 patients were available for analysis, with the top 10 cancers grouped as Common (67%), 13 cancers grouped with Intermediate (24%), and 37 cancers as Rare (9%). Rare cancers had higher rates of children who were older and Black. 5-year survival increased from 63% to 86% across all cancers from the 1970s to the 2010s. The hazard ratio (HR) for mortality decreased from the reference point of 1 in the 1970s to 0.27 (95% CI: 0.25-0.30) in the 2010s in Common cancers, while the HR only dropped to 0.60 (0.49-0.73) over that same period for rare cancers. Pediatric oncology patients have experienced dramatic improvement in mortality since the 1970s, with mortality falling by nearly 75% in common cancers. Unfortunately, rare pediatric cancers continue to lag behind more common and therefore better studied cancers, highlighting the need for a renewed focus on research efforts for children with these rare diseases.

Radiation therapy targets tumor tissue and requires children to lay still, often necessitating sedation. Historically anesthesiologists provided procedural sedation, but pediatric critical care physicians now regularly administer sedation outside the operating room. Procedural sedation for radiation poses unique challenges. The objective was to evaluate the success and assess complications of repeated sedations for radiation performed by pediatric critical care physicians. We performed a single-center, retrospective case series of children who received procedural sedation for radiation therapy by PICU physicians. The primary outcome was success, defined as completion of radiation treatment. Secondary outcomes included type of medication, dosing, tolerance, and complications requiring intervention. In our sample, 55 patients underwent 1174 sedation instances (mean 19.8 per patient). Patients had a mean age of 4.7 years (SD3.4), and weight of 20.2 kg (SD11.9). All patients had an ASA of 2 or 3. All patients had either a brain tumor or a non-mediastinal solid tumor. The success rate was 99.8%. The mean duration of sedation was 30.7 min (SD12.4). All sedations included propofol as a first agent with a mean bolus 3.3 mg/kg (SD1.4) and drip rate 148.7 mcg/kg/min (SD39.7). 4.4% of sedations required a second agent medication. There was no significant effect of repeated sedation with regards to the medication amount received (p = 0.97). Laryngospasm occurred during 0.2% of sedations. No patients required bag-mask ventilation, intubation, or chest compressions; no patients died during sedation. Pediatric critical care physicians can perform procedural sedation for radiation therapy successfully.

In adults, there is a link between socioeconomic status (SES) and cancer prognosis, notably due to increased time to diagnosis (TTD) in deprived population leading to the dissemination of the disease. In children, such an association has not been clearly reported. The objective of our study was to assess the impact of SES on TTD of childhood cancer and its potential consequences on cancer prognosis. We carried out a multicenter retrospective study based on the LOGAFTER multi centric database. We studied SES at the individual level (parental professions, family structure) and the ecological level (EDI score, travel time by car). We assessed the factors potentially associated with an increased TTD with a Cox regression model, and we illustrated TTD by categories by using Kaplan-Meier curves. 854 children were included. The median time to diagnosis was 28 days [12;64]. TTD differed significantly according to the type of tumor. An usual care pathway did not impact TTD. However, an initial management by professionals not usually involved in the specific childhood cancer context increased TTD. None of the SES ecological variables were strictly associated with an impact on TTD, and a trend was noted for single-parent families (increased TTD, p = 0.057). In our cohort, TTD did not impact on the vital and relapse status. In this study, the impact of SES on TTD in children on both the individual and ecological levels was not clear. However, we noted some keys at the individual scale that require further investigation to explain potential associations.

In prospective Japanese studies of pediatric renal tumors, 5-year event-free survival and overall survival (OS) for patients with nephroblastoma ranges from 75-90% and 89-97%, respectively. However, treatments strategies for recurrent nephroblastoma in Japanese patients remain unclear. This retrospective study aimed to inform the development of treatment strategies by analyzing the long-term results and side effects of salvage therapies for recurrent nephroblastoma in Japan. A questionnaire survey involving 41 institutions (74 patients) collected clinical data on recurrent cases reported to the Renal Tumor Committee of the Japan Children's Cancer Group. Survey forms from 54 cases were evaluated. Median time to recurrence was 9.5 months among 51 patients without underlying disorders. Recurrence occurred at lung-only in 18 patients and at other sites in 33. The 5-year OS for all 51 patients was 70.6%, with recurrent disease causing death in 15 patients and one patient dying from treatment-related complications. Patients with lung-only recurrence had higher 5-year OS rates than those with other-site recurrence. Initial chemotherapy intensity also affected prognosis, with lower intensity associated with higher 5-year OS. In 17 survivors with lung-only recurrence, the most frequent treatment approach combined chemotherapy, surgery and radiotherapy. Conventional chemotherapy included platinum-containing regimens and/or Regimen I-based treatment containing cyclophosphamide and etoposide. Salvage therapies showed remarkable effectiveness for patients with lung-only recurrence or low intensity of the initial chemotherapy, highlighting the need to standardize prospective studies for post-recurrence treatment and identify risks of late complications for long-term survivors.

Application of evidenced-based practices is often lacking in medical education. Increased recognition that methods of knowledge delivery based in relevant learning theories are more effective has led to improved ability to meet the needs of adult learners. We designed a study to assess approaches to education for Pediatric Hematology/Oncology (PHO) trainees and identify opportunities for incorporation of evidence-based practices. A national survey was shared with program directors (PDs) of PHO programs to investigate current trends in education design. Respondents were contacted via email, the survey was distributed by REDCap, and data were collected from April-July 2023. Quantitative data were analyzed descriptively and free-text responses using directed content analysis. Of the 77 eligible participants, 46 completed the survey (59.74% response rate), representing various geographic regions and class sizes. Respondents reported a wide range of familiarity with adult learning theory (range 1-5, median 3) and self-regulated learning (range 1-5, median 2). While programs employed active learning strategies to varying degrees, the lecture format was the most used method of education delivery. PDs recognized the need for development in several domains, including incorporation of educational frameworks, support for structure and content of didactics, and implementation of feedback related to education sessions. Differences in approaches were described, revealing a wide range of familiarity with and application of specific educational theories, as well as inconsistent efforts to consider principles of adult learning theory and self-regulated learning. These data demonstrate opportunities for targeted education and curriculum development.

Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is a costimulatory receptor exhibiting a potent inhibitory signal on antigen-activated immune responses. A soluble form, sCTLA-4, has been identified and was found to be increased in several autoimmune diseases. We aimed to evaluate serum levels of sCTLA-4 in different immune cytopenias, and to determine its possible relation to the disease activity. We measured serum levels of sCTLA-4 in 47 patients with immune cytopenias and compared them to 47 age- and sex-matched healthy controls. sCTLA-4 levels were significantly higher in patients with immune cytopenias compared to healthy controls (p < 0.001), however, levels were comparable between different groups of immune cytopenias (p = 0.084). Serum sCTLA-4 inversely correlated with age at diagnosis and hemoglobin level (p = 0.048, and p = 0.039 respectively), while it directly correlated with disease duration (p = 0.023) as well as markers of hemolysis including reticulocyte count, serum LDH and indirect bilirubin (p = 0.025; p = 0.019; p = 0.004 respectively). In the AIHA group, serum sCTLA-4 levels were significantly lower in patients in remission compared to patients with active disease (p = 0.026). Children with immune cytopenia exhibit significantly higher levels of circulating sCTLA-4 which correlated with disease activity, yet the prognostic significance and its use to tailor treatment regimen require additional studies.

This study investigates the correlation between circulating tumor cells (CTCs) in peripheral blood and the clinical characteristics and prognosis of advanced pediatric neuroblastoma (NB). We conducted a retrospective analysis of 144 children with advanced NB who underwent comprehensive treatment. Detailed clinical data were collected, and CTCs were detected using a negative enrichment method combined with immunofluorescence technology. Prognostic evaluation criteria and cutoff values for CTCs were established using ROC curve analysis. Univariate and Cox multivariate regression analyses identified independent risk factors impacting prognosis. Patients were categorized into high and low-expression groups based on optimal cutoff values determined with X-tile software. The high expression group had a significantly higher incidence of disease progression (p < 0.001), maximum tumor diameter ≥10 cm (p = 0.004), undifferentiated subtype (p = 0.034), and stage IV disease (p = 0.007) compared to the low expression group. CTCs were notably higher in patients with progression compared to those with mitigation (p < 0.001), in those with maximum tumor diameter ≥10 cm compared to <10 cm (p < 0.001), and in stage IV compared to stage III patients (p = 0.036). The AUC values for maximum tumor diameter, degree of differentiation, and tumor stage were 0.703, 0.669, 0.574, and 0.598, respectively. The detection of CTCs provides significant insights into the clinical characteristics and prognosis of advanced pediatric NB, highlighting its potential as a prognostic tool.

Measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an independent risk factor for relapse in patients with acute lymphoblastic leukemia (ALL). This study aimed to assess the efficacy, safety, and immune reconstitution of chimeric antigen receptor T-cell (CAR-T) therapy in patients with molecular relapse after allo-HSCT. Eleven patients with molecular relapse of B-cell-ALL who underwent CAR-T therapy after allo-HSCT were enrolled. The rate of MRD negativity after a month of CAR-T infusion was 81.8%. Patients who bridged to second-HSCT after CAR-T therapy (n = 3) showed a trend of higher 3-year leukemia-free survival and 3-year overall survival than those who did not (n = 8; 100% vs. 75.0%; 95% CI, 45.0-104.9%; p = 0.370). No treatment-related mortalities were observed. Among patients who did not bridge to second-HSCT and remained in complete remission until the last follow-up (n = 6), five of them had not recovered normal immunoglobulin concentrations with a median follow-up of 43 months. CAR-T therapy may be a safe and effective treatment strategy to improve survival after allo-HSCT; however, the problem of prolonged hypogammaglobulinemia in patients who do not bridge to second-HSCT is worth noting.