Outcome of infants with acute lymphoblastic leukemia treated with the Chinese Children's Cancer Group Acute Lymphoblastic Leukemia 2015 study protocol.

Not available.

[Analysis of 41 cases of non-metastatic Ewing's sarcoma in children]. / 儿童非转移性尤文肉瘤41例分析.

OBJECTIVES: To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). METHODS: A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. RESULTS: Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. CONCLUSIONS: A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.

Bone marrow relapse in stage 4 neuroblastoma of children in Shanghai.

OBJECTIVE: To characterize the epidemiological, clinical, and molecular features of bone marrow relapse in high-risk neuroblastoma (HR-NB) and to identify potential prognostic indicators and therapeutic approaches for this specific subset within the Shanghai pediatric oncology landscape. METHODS: A retrospective study was conducted on 256 patients diagnosed with stage 4 neuroblastoma at two major pediatric hospitals in Shanghai, China, between 2008 and 2018. Patient data was collected, including demographic information, treatment regimens, and outcomes. Kaplan-Meier method and log-rank test were used for overall survival (OS) and event-free survival (EFS) analysis. RESULTS: The study revealed that bone marrow relapse affected 50.78% of patients, making it the most frequent relapse site. Patients with bone marrow involvement at diagnosis face an increased risk of subsequent bone marrow relapse. Age over 18 months, multiple metastatic sites, and the absence of autologous stem cell transplantation (ASCT) were identified as significant risk factors for bone marrow relapse. The 3-year OS and EFS rates of patients with bone marrow relapse were 32.5% and 32.5%, respectively. Patients receiving ASCT demonstrated significantly higher survival rates. The lack of ASCT at diagnosis was significantly correlated with lower survival rates, particularly in patients experiencing bone marrow relapse. CONCLUSION: The study provides valuable insights into the challenges posed by bone marrow relapse in the setting of high-risk neuroblastoma. It emphasizes the need for tailored therapeutic approaches to improve outcomes, potentially involving novel targeted agents and immunotherapies. The study underscores the poor prognosis associated with bone marrow relapse in HR-NB and the urgent need for further research to optimize risk stratification and therapeutic strategies, including prospective investigation and the integration of advanced molecular profiling techniques.

Prognostic implications of CD9 in childhood acute lymphoblastic leukemia: insights from a nationwide multicenter study in China.

The outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter. To determine its precise prognostic significance, we analyzed a nationwide, multicenter, uniformly treated cohort of childhood ALL cases, where CD9 status was defined by flow cytometry on diagnostic samples of 3781 subjects. CD9 was expressed in 88.5% of B-ALL and 27.9% of T-ALL cases. It conferred a lower 5-year EFS and a higher CIR in B-ALL but not in T-ALL patients. The prognostic impact of CD9 was most pronounced in the intermediate/high-risk arms and those with minimal residual diseases, particularly at day 19 of remission induction. The adverse impact of CD9 was confined to specific cytogenetics, notably BCR::ABL1+ rather than KMT2A-rearranged leukemia. Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL.

Computed tomography-based radiomics to assess risk stratification in pediatric malignant peripheral neuroblastic tumors.

This study aimed to develop and validate an analysis system based on preoperative computed tomography (CT) to predict the risk stratification in pediatric malignant peripheral neuroblastic tumors (PNTs). A total of 405 patients with malignant PNTs (184 girls and 221 boys; mean age, 33.8 ±â€…29.1 months) were retrospectively evaluated between January 2010 and June 2018. Radiomic features were extracted from manually segmented tumors on preoperative CT images. Spearman's rank correlation coefficient and the least absolute shrinkage and selection operator (LASSO) were used to eliminate redundancy and select features. A risk model was built to stratify low-, intermediate-, and high-risk groups. An image-defined risk factor (IDRFs) model was developed to classify 266 patients with malignant PNTs and one or more IDRFs into high-risk and non-high-risk groups. The performance of the predictive models was evaluated with respect to accuracy (Acc) and receiver operating characteristic (ROC) curve, including the area under the ROC curve (AUC). The risk model demonstrated good discrimination capability, with an area under the curve (AUC) of 0.903 to distinguish high-risk from non-high-risk groups, and 0.747 to classify intermediate- and low-risk groups. In the IDRF-based risk model with the number of IDRFs, the AUC was 0.876 for classifying the high-risk and non-high-risk groups. Radiomic analysis based on preoperative CT images has the potential to stratify the risk of pediatric malignant PNTs. It had outstanding efficiency in distinguishing patients in the high-risk group, and this predictive model of risk stratification could assist in selecting optimal aggressive treatment options.

Interferon stimulated immune profile changes in a humanized mouse model of HBV infection.

The underlying mechanism of chronic hepatitis B virus (HBV) functional cure by interferon (IFN), especially in patients with low HBsAg and/or young ages, is still unresolved due to the lack of surrogate models. Here, we generate a type I interferon receptor humanized mouse (huIFNAR mouse) through a CRISPR/Cas9-based knock-in strategy. Then, we demonstrate that human IFN stimulates gene expression profiles in huIFNAR peripheral blood mononuclear cells (PBMCs) are similar to those in human PBMCs, supporting the representativeness of this mouse model for functionally analyzing human IFN in vivo. Next, we reveal the tissue-specific gene expression atlas across multiple organs in response to human IFN treatment; this pattern has not been reported in healthy humans in vivo. Finally, by using the AAV-HBV model, we test the antiviral effects of human interferon. Fifteen weeks of human PEG-IFNα2 treatment significantly reduces HBsAg and HBeAg and even achieves HBsAg seroconversion. We observe that activation of intrahepatic monocytes and effector memory CD8 T cells by human interferon may be critical for HBsAg suppression. Our huIFNAR mouse can authentically respond to human interferon stimulation, providing a platform to study interferon function in vivo. PEG-IFNα2 treatment successfully suppresses intrahepatic HBV replication and achieves HBsAg seroconversion.

Effect of the tyrosine kinase inhibitors on the growth in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: a case-control study.

Background: First-generation ABL-targeted tyrosine kinase inhibitor (TKI) imatinib is known to retard growth in children but it is not known if the second-generation ABL-targeted TKI dasatinib has the same effect. We aimed to determine the impact of the first- or second-generation TKI on the growth of children treated for Philadelphia chromosome-positive (Ph+) childhood acute lymphoblastic leukemia (ALL). Methods: We evaluated the longitudinal growth changes in 140 children with Ph+ ALL treated with imatinib or dasatinib in additional to intensive cytotoxic chemotherapy and 280 matched controls treated with the same intensity of cytotoxic chemotherapy without TKI on Chinese Children's Cancer Group ALL-2015 protocol between 2015 and 2019. We retrospectively reviewed the height data obtained during routine clinic visits at 4 time points: at diagnosis, the end of therapy, 1 year and 2 years off therapy. Height z Scores were derived with the aid of WHO Anthro version 3.2.2 and WHO AnthroPlus version 1.0.4, global growth monitoring tool. Findings: This study consisted only patients who have completed all treatment in continuous complete remission without major events, including 33 patients randomized to receive imatinib, 43 randomized to receive dasatinib, and 64 assigned to receive dasatinib. Similar degree of loss of height z scores from diagnosis to the end of therapy was observed for the 33 imatinib- and the 107 dasatinib-treated patients (median △ = -0.84 vs. -0.88, P = 0.41). Adjusting for height z score at diagnosis, puberty status, and sex, there was no significant difference in the longitudinal mean height z scores between patients treated with imatinib and those with dasatinib (0.08, 95% CI, -0.22 to 0.38, P = 0.60). The degree of loss of height z scores from diagnosis to end of therapy was significantly greater in the 140 TKI-treated patients than the 280 controls (median △ = -0.88 vs. -0.18, P < 0.001). The longitudinal mean height z scores in the TKI-treated patients were significantly lower than those of the controls (-0.84, 95% CI, -0.98 to -0.69; P < 0.001). Interpretation: These data suggest that dasatinib and imatinib have the similar adverse impact on the growth of children with Ph+ ALL. Funding: This study was supported by the National Natural Science Foundation of China (grant 81670136 [JCai and JT]), the fourth round of Three-Year Public Health Action Plan (2015-2017; GWIV-25 [SS]), Shanghai Health Commission Clinical Research Project (202140161 [JCai]), the US National Cancer institute (CA21765 [C-H Pui]), and the American Lebanese Syrian Associated Charities (CC, JJY, and C-HP). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health.

Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia.

For around half of the pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients, the molecular mechanism of relapse remains unclear. To fill this gap in knowledge, here we characterize the chromatin accessibility landscape in pediatric relapsed B-ALL. We observe rewired accessible chromatin regions (ACRs) associated with transcription dysregulation in leukemia cells as compared with normal B-cell progenitors. We show that over a quarter of the ACRs in B-ALL are in quiescent regions with high heterogeneity among B-ALLs. We identify subtype-specific and allele-imbalanced chromatin accessibility by integrating multi-omics data. By characterizing the differential ACRs between diagnosis and relapse in B-ALL, we identify alterations in chromatin accessibility during drug treatment. Further analysis of ACRs associated with relapse free survival leads to the identification of a subgroup of B-ALL which show early relapse. These data provide an advanced and integrative portrait of the importance of chromatin accessibility alterations in tumorigenesis and drug responses.

Causes of death and treatment-related mortality in newly diagnosed childhood acute lymphoblastic leukemia treatment with Chinese Children's Cancer Group study ALL-2015.

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).

Safety and efficacy of co-administration of CD19 and CD22 CAR-T cells in children with B-ALL relapse after CD19 CAR-T therapy.

BACKGROUND: CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed or refractory pediatric B-lineage acute lymphoblastic leukemia (B-ALL). However, poor results are obtained when the same product is reused in patients who relapse after CAR-T. Therefore, there is a need to explore the safety and efficacy of co-administration of CD19- and CD22-targeted CAR-T as a salvage second CAR-T therapy (CART2) in B-ALL patients who relapse after their first CD19 CAR-T treatment (CART1). METHODS: In this study, we recruited five patients who relapsed after CD19-targeted CAR-T. CD19- and CD22-CAR lentivirus-transfected T cells were cultured separately and mixed before infusion in an approximate ratio of 1:1. The total dose range of CD19 and CD22 CAR-T was 4.3 × 106-1.5 × 107/kg. Throughout the trial, we evaluated the patients' clinical responses, side effects, and the expansion and persistence of CAR-T cells. RESULTS: After CART2, all five patients had minimal residual disease (MRD)-negative complete remission (CR). The 6- and 12-month overall survival (OS) rates were 100%. The median follow-up time was 26.3 months. Three of the five patients bridged to consolidated allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CART2 and remained in MRD-negative CR at the cut-off time. In patient No. 3 (pt03), CAR-T cells were still detected in the peripheral blood (PB) at 347 days post-CART2. Cytokine release syndrome (CRS) only occurred with a grade of ≤ 2, and no patients experienced symptoms of neurologic toxicity during CART2. CONCLUSIONS: Mixed infusion of CD19- and CD22-targeted CAR-T cells is a safe and effective regimen for children with B-ALL who relapse after prior CD19-targeted CAR-T therapy. Salvage CART2 provides an opportunity for bridging to transplantation and long-term survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000032211. Retrospectively registered: April 23, 2020.

Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG-ALL-2015: A multicenter study.

BACKGROUND: Contemporary risk-directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome. METHODS: The authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL-2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate-risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation. RESULTS: The overall 5-year event-free survival was 84.4% (95% confidence interval [CI], 80.6-88.3) and 5-year overall survival 88.9% (95% CI, 85.5-92.4). Independent factors associated with lower 5-year event-free survival were male sex (80.4%, [95% CI, 74.8-86.4] vs. 88.9%, [95% CI, 84.1-93.9] in female, p = .03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2-87.4] vs. 87.1%, [95% CI, 83.4-90.9] in patients with negative MRD, p < .001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5-year event-free survival (33.3% [95% CI, 11.6-96.1] vs. 83.0% [95% CI, 77.5-88.9] in the other 192 male patients, p < .001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2-14.5], p < .001). CONCLUSIONS: These data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL.

Venous thromboembolism in children with acute lymphoblastic leukemia in China: a report from the Chinese Children's Cancer Group-ALL-2015.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.

High titers of neutralizing antibodies in the blood fail to eliminate SARS-CoV-2 viral RNA in the upper respiratory tract.

Retest-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA, as a unique phenomenon among discharged individuals, has been demonstrated to be safe in the community. Still, the underlying mechanism of viral lingering is less investigated. In this study, first, we find that the frequency of viral RNA-positive retesting differs among variants. Higher ratios of viral RNA-positive retest were more frequently observed among Delta (61.41%, 514 of 837 cases) and Omicron (39.53%, 119 of 301 cases) infections than among ancestral viral infection (7.27%, 21 of 289 cases). Second, the tissues where viral RNA reoccurred were altered. Delta RNA reoccurred mainly in the upper respiratory tract (90%), but ancestral virus RNA reoccurred mainly in the gastrointestinal tract (71%). Third, vaccination did not reduce the frequency of viral RNA-positive retests, despite high concentrations of viral-specific antibodies in the blood. Finally, 37 of 55 (67.27%) Delta-infected patients receiving neutralizing antibody therapy become viral RNA retest positive when high concentrations of neutralizing antibodies still patrol in the blood. Altogether, our findings suggest that the presentence of high titers of neutralizing antibodies in the blood is incompetent in clearing residual viral RNA in the upper respiratory tract.

Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial.

PURPOSE: We determined the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory disease or high-risk hematologic or isolated extramedullary relapse of B-acute lymphoblastic leukemia. PATIENTS AND METHODS: This phase II trial enrolled 225 evaluable patients age ≤ 20 years between September 17, 2019, and December 31, 2021. We first conducted a safety run-in stage to determine the recommended dose. After interim analysis of the first 30 patients treated (27 at the recommended dose) showing that the treatment was safe and effective, the study enrolled additional patients according to the study design. RESULTS: Complete remission was achieved in 99.0% of the 194 patients with refractory leukemia or hematologic relapse, all negative for minimal residual disease. Their overall 12-month event-free survival (EFS) was 73.5% (95% CI, 67.3 to 80.3). Relapse occurred in 43 patients (24 with CD19+/CD22+ relapse, 16 CD19-/CD22+, one CD19-/CD22-, and two unknown). Consolidative transplantation and persistent B-cell aplasia at 6 months were associated with favorable outcomes. The 12-month EFS was 85.0% (95% CI, 77.2 to 93.6) for the 78 patients treated with transplantation and 69.2% (95% CI, 60.8 to 78.8) for the 116 nontransplanted patients (P = .03, time-dependent covariate Cox model). All 25 patients with persistent B-cell aplasia at 6 months remained in remission at 12 months. The 12-month EFS for the 20 patients with isolated testicular relapse was 95.0% (95% CI, 85.9 to 100), and for the 10 patients with isolated CNS relapse, it was 68.6% (95% CI, 44.5 to 100). Cytokine release syndrome developed in 198 (88.0%) patients, and CAR T-cell neurotoxicity in 47 (20.9%), resulting in three deaths. CONCLUSION: CD19-/CD22-CAR T-cell therapy achieved relatively durable remission in children with relapsed or refractory B-acute lymphoblastic leukemia, including those with isolated or combined extramedullary relapse.[Media: see text].

Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity.

PURPOSE: Neuroblastoma arises from developmental block of embryonic neural crest cells and is one of the most common and deadly pediatric tumors. However, the mechanism underlying this block is still unclear. Here, we show that targeting Rho guanine nucleotide exchange factor 12 (ARHGEF12, also named LARG) promotes MYCN degradation and neuroblastoma differentiation, leading to reduced neuroblastoma malignancy. METHODS: The neuroblastoma TARGET dataset was downloaded to assess ARHGEF12 expression. Cell differentiation, proliferation, colony formation and cell migration analyses were performed to investigate the effects of ARHGEF12 knockdown on neuroblastoma cells. Western blotting and immunohistochemistry were employed to determine protein expression. Animal xenograft models were used to investigate antitumor effects after ARHGEF12 knockdown or treatment with the ARHGEF12 inhibitor Y16 in vivo. RESULTS: We found that the expression level of ARHGEF12 was higher in neuroblastoma than in better-differentiated ganglioneuroblastoma. Knockdown of ARHGEF12 promoted neuroblastoma differentiation, decreased stemness-related gene expression, and increased differentiation-related gene expression. ARHGEF12 knockdown reduced tumor growth, and the resulting tumors showed bigger tumor cells compared to those in control neuroblastoma xenografts. In addition, it was found that ARHGEF12 knockdown promoted MYCN ubiquitination and degradation in MYCN-amplified tumors through RhoA/ROCK/GSK3ß signaling. Targeting ARHGEF12 with the small molecular inhibitor Y16 induced cell differentiation and attenuated neuroblastoma tumorigenicity. CONCLUSION: Our findings provide new insight into the mechanism by which ARHGEF12 regulates neuroblastoma tumorigenicity and suggest a translatable therapeutic approach by targeting ARHGEF12 with a small molecular inhibitor.

Association between body mass index at diagnosis and outcomes in Chinese children with newly diagnosed acute lymphoblastic leukemia.

PURPOSE: Studies of the association between body mass index (BMI) at diagnosis and treatment outcome in children with acute lymphoblastic leukemia (ALL) have yielded inconsistent results. Hence, we conducted a retrospective study in a large cohort of Chinese children with ALL treated with contemporary protocols. PATIENTS AND METHODS: A total of 1437 children (62.1% male; median age at diagnosis 5.7 years, range: 2.3-16.3 years) were enrolled in two consecutive clinical trials at the Shanghai Children's Medical Center. The rates of overall survival, event-free survival, relapse, treatment-related mortality, and adverse events were compared among patients who were underweight (BMI < 5th percentile), at a healthy weight (5th to 85th percentile), overweight (>85th to <95th percentile), and obese (≥95th percentile). RESULTS: At diagnosis, 91 (6.3%) patients were underweight, 1070 (74.5%) were at a healthy weight, 91 (6.3%) were overweight, and 185 (12.9%) were obese. No significant association was found between weight status and 5-year overall survival, event-free survival, or relapse in the overall cohort. When analyzed as a continuous variable, a higher BMI Z-score was associated with treatment-related mortality (hazard ratio 1.33 (95% confidence interval [CI], 1.05-1.68%), p = 0.02). The treatment-related mortality rate was higher in the overweight (5.5%, 95% CI 0.8-10.2%) and obese (3.2%, 95% CI 0.6-5.8%) groups compared with the underweight (0.0%) and healthy-weight groups (1.9%, 95% CI 1.1-2.7%; p = 0.04). Multivariable analysis showed that children who were overweight had a higher risk of treatment-related mortality (hazard ratio 3.8, 95% CI 1.3-11.4). CONCLUSION: While body weight status was not associated with event-free survival or overall survival, overweight patients were at higher risk of treatment-related mortality.

Psychosocial outcomes in Chinese survivors of pediatric cancers or bone marrow failure disorders: A single-center study.

BACKGROUND/OBJECTIVES: Most of the studies on functional outcomes in pediatric survivors of cancers and bone marrow failure disorders have been conducted in North American, European, and Oceanian populations, with few studies having been performed in China. The objective of this study was to evaluate psychosocial outcomes in a cohort of Chinese pediatric survivors diagnosed with cancer or conditions requiring hematopoietic stem cell transplantation (HSCT), and to identify clinical and behavioral factors associated with adverse psychosocial outcomes. METHODS: This was a cross-sectional survey study. We recruited pediatric survivors of cancer or inherited disorder requiring HSCT at ≤18 years old and were ≥6 months post-treatment. Parents completed the St. Jude Children's Research Hospital After Completion of Therapy questionnaire to report their child's emotional functioning, social functioning, attention/concentration and behavior. Multivariable general linear modeling was used to identify clinical, treatment and behavioral factors associated with psychosocial outcomes, adjusting for sex, age and cancer diagnoses. RESULTS: Ninety-five pediatric survivors were recruited (62.1% male; mean [standard deviation] age 9.7 [3.4] years; 4.1 [2.6] years post-diagnosis). They were diagnosed with bone marrow failure disorders (23.2%), hematological malignancies (45.3%) or solid tumors (23.2%). Compared with survivors with no current health problems, those with more than one current health problem performed worse in emotional functioning (Estimate = 2.42, SE = 0.88, P = 0.008) and social functioning (Estimate = 2.90, SE = 1.64, P = 0.03). Higher pain interference was significantly associated with worse emotional functioning (Estimate = 0.19, SE = 0.08, P = 0.03) and attention functioning (Estimate = 0.26, SE = 0.11, P = 0.03). Compared with survivors who reported less sleep problems, those who had more sleep problems demonstrated poorer emotional functioning (Estimate = 0.30, SE = 0.08, P = 0.001). Survivors who had a longer duration of screen usage per day reported more impairment on attention and behavior functioning than those who had a shorter duration of screen usage per day (both P<0.5). CONCLUSION: Survivors who were diagnosed at a younger age or had unaddressed/untreated health problems may require additional psychological evaluation. The implementation of psychosocial assessments during routine long-term follow-up care may help to identify high-risk patients during the early phase of survivorship. Rehabilitation interventions should address modifiable behavioral factors (e.g. sleep habits, screen time and chronic pain).

A prospective multicenter study on varicella-zoster virus infection in children with acute lymphoblastic leukemia.

Background and methods: The study evaluated prognostic factors associated with varicella-zoster virus (VZV) infection and mortality in children with acute lymphoblastic leukemia (ALL) using data from the multicenter Chinese Children's Cancer Group ALL-2015 trial. Results: In total, 7,640 patients were recruited, and 138 cases of VZV infection were identified. The incidence of VZV infection was higher in patients aged ≥ 10 years (22.5%) and in patients with the E2A/PBX1 fusion gene (11.6%) compared to those aged < 10 years (13.25%, P = 0.003) or with other fusion genes (4.9%, P = 0.001). Of the 10 deaths in children with ALL and VZV infection, 4 resulted from VZV complications. The differences between groups in the 5-year overall survival, event-free survival, cumulative recurrence, and death in remission were not statistically significant. The proportion of complex infection was higher in children with a history of exposure to someone with VZV infection (17.9% vs. 3.6%, P = 0.022). Conclusion: VZV exposure was associated with an increased incidence of complex VZV infection and contributed to VZV-associated death in children with ALL.