Objective:To analyze the clinical characteristics of adverse reactions caused by dinutuximab β for the treatment of neuro-blastoma(NB)in China and to provide safety evidence for the rational use of dinutuximab β in clinical practice.Methods:Clinical data were retrospectively collected from 16 pediatric patients with NB who had been treated with dinutuximab β at Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to November 2023,and the adverse reactions caused by dinutuximab β were summarized and analyzed.Results:The male-to-female ratio was 5:3 among the 16 children with NB.The retroperitoneum was the main initial site of involvement,accounting for 75%.Thirteen(81.25%)patients had high-risk NB.The adverse reactions caused by dinutuximab β mainly included decreased hemoglobin,fever,vomiting,and diarrhea.The inci-dence of adverse reactions was highest in the first course of treatment,and the median time of adverse reactions was 2-5 days.Conclu-sion:Targeted monitoring should be carried out at an early stage during dinutuximab β administration.Adverse reactions should be de-tected and managed early to ensure the safety of medication for children.

Neuroblastoma is a common extracranial solid tumors in children，and patients with high-risk disease have poor prognosis. Since the pathogenesis of neuroblastoma has not been fully elucidated，early diagnosis and timely，effective clinical intervention are key strategies to improve survival in affected children. As a neuroendocrine tumor，neuroblastoma is characterized by abnormal secretion of catecholamine compounds，the synthesis and release of which are closely associated with both diagnosis and prognosis. This review summarizes the biosynthetic and metabolic pathways of catecholamines and their clinical applications in neuroblastoma，and further discusses the molecular mechanisms by which catecholamines contribute to neuroblastoma progression.

Hodgkin lymphoma（HL）is one of the common pediatric malignancies（especially in adolescents）. The prognosis of pediatric patients with HL is excellent with traditional first-line treatment regimens involving short-course，high-dose combination chemotherapy and low-intensity radiotherapy，resulting in an overall response rate of 90%. However，10%-25% of pediatric HL patients are estimated to have relapsed/refractory（r/r）disease，and survivors of pediatric HL are at risk of late effects caused by traditional treatment regimens. For children with r/r HL，novel therapies，such as brentuximab vedotin，immune checkpoint inhibitors and immune cell therapy，including chimeric antigen receptor T-cell therapy and EBV-specific cytotoxic T lymphocytes are an integral part of their salvage treatment and consolidation treatment after hematopoietic stem cell transplantation. Furthermore，combining novel therapies with first-line treatment regimens for pediatric HL may help enhance therapeutic efficacy and reduce treatment toxicity. This review is aimed to describe current advances in novel therapies for pediatric HL，and serve as a reference for clinical practice.

Objective:To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation.Methods:This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis.Results:Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions:The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

Objective:To study the survival and prognostic factors for the recurrent extracranial malignant germ cell tumors (MGCTs) in children, and to explore feasible salvage treatment.Methods:A retrospective study.Pediatric patients with recurrent extracranial MGCTs diagnosed in Shanghai Children′s Medical Center between January 2010 and January 2020 were retrospectively recruited.Comprehensive treatment regimens included surgery, chemotherapy and radiation.Kaplan-Meier survival analysis and Cox regression model were employed to analyze the survival and prognostic factors for children with recurrent extracranial MGCTs.Results:A total of 172 children with extracranial MGCTs were treated, including 21 (12.2%) recurrent cases.The median time of MGCT recurrence after the end of the first treatment was 11 months.Finally, 19 patients were recruited after excluding 2 non-eligible cases, including 10 boys and 9 girls with the age at recurrence of 26 (8-170) months.The follow-up time was 57 (13-122) months.Salvage chemotherapy, complete resection and radiotherapy were performed in 16, 14 and 4 patients, respectively.The 4-year overall survival (4yr-OS) rate was (82.5±9.2)%(19 cases). The 4yr-OS rate was significantly higher in patients managed with surgery but without adjuvant chemotherapy at the initial treatment (13 cases) than those managed with chemotherapy at the initial treatment (6 cases)[(92.3±7.4)% vs.(60.0%±21.9)%, P=0.002]. Univariant and Cox multivariant regression analyses showed that failure to achieve the normal range of alpha fetoprotein after 3 cycles of chemotherapy significantly influenced the survival of recurrent extracranial MGCTs. Conclusions:For patients with recurrent extracranial MGCTs, comprehensive treatment approaches like complete surgical resection, chemotherapy, and radiotherapy offer a favorable survival rate.Specifically, recurrent and re-treated patients who initially received surgery alone without adjuvant chemotherapy have a higher survival rate compared to those who received chemotherapy during the initial treatment.

Objective:To investigate the incidence of abnormal bone mineral density (BMD) in male patients with alcoholic cirrhosis.Methods:Clinical data of 72 patients with alcoholic cirrhosis admitted in Beijing Ditan Hospital, Capital Medical University from March 2017 to July 2023 were enrolled as study group, and 40 age-and BMI-matched non-hepatopathy subjects were selected as control group.The incidence of abnormal BMD were compared between two groups. The serum levels of osteocalcin (OC), total procollagen type 1 amino-terminal propeptide (TP1NP), β-C-terminal telopeptide of typeⅠcollagen (CTX) and 25-hydroxy vitamin D [25-(OH)VD] were measured and compared among patients with different Child-Pugh grades.Results:Among 72 alcoholic cirrhosis patients, there were 54 cases (75.0%) complicated with abnormal BMD, including 21 cases (29.2%) of bone loss and 33 cases (45.8%) of osteoporosis. In control group there were 15 subjects with abnormal bone mineral density, including 9 cases (22.5%) of bone loss and 6 cases (15.0%) of osteoporosis( χ2=5.623 and 15.900,both P<0.05). The average BMDs of L1-L4, femoral neck, intertrochanteric region and trochanter of the femur in patients with alcoholic cirrhosis were significantly lower than those in control group ( t=3.574, 8.640, 7.282, 7.958, 3.755, 5.573, 5.026,all P<0.05); the average BWDs of L1-L3 and hip joint in patients with Child-Pugh C were significantly lower than those in patients with Child-Pugh A and B ( t=1.414, 1.699, 3.786, 2.590, 8.763, 2.581, 1.392, 6.232,all P<0.05). The serum levels of 25-(OH)VD in alcoholic cirrhosis patients with Child-Pugh C grade were significantly lower than those with Child-Pugh A and B ( t=3.969 and 2.911, P<0.05); the serum calcium levels in patients with Child-Pugh C grade were lower than those with Child-Pugh A( t=3.627, P<0.05); while the TP1NP levels in patients with Child-Pugh C were higher than those with Child-Pugh A and B grades( t=6.722 and 5.034, P<0.05).The Child-Pugh grade was negatively correlated with 25-(OH)VD level( β=-0.767, P<0.05)and positively correlated with TP1NP level ( β=2.186, P<0.05). Conclusion:The incidence of bone loss and osteoporosis in patients with alcoholic cirrhosis is increased significantly, and the deterioration of their liver function is closely associated with an increased TP1NP level and decreased 25-(OH)VD levels.

Neuroblastoma(NB)is the most common extracranial solid tumor in children.It is notable for highly heterogeneous and associated with tumor histologic classification and differentiation status, with ganglioneuroma representing fully mature and differentiated NB.Differentiation therapy reduces the adverse reactions caused by treatment without affecting normal cells and tissues by inducing the redifferentiation of NB cells, and has a good development prospect in the maintenance treatment of high-risk NB patients.Therefore, studying the key molecules and signaling pathways affecting NB differentiation is significant to further clarify the pathogenesis and improve the prognosis of neuroblastoma.This article reviews the important molecules related to NB cell differentiation, signaling pathways and the research progress of differentiation induction therapy.

Cisplatin is a broad-spectrum and highly effective chemotherapeutic agent, with a dose-dependent therapeutic effect.Unfortunately, high-does therapy is limited by ototoxicity, nephrotoxicity and neurotoxicity.Ototoxicity is a common and serious complication after cisplatin chemotherapy, which has greatly debilitating effect on patients′ quality of life.Currently, there are no FDA-approved drugs available to prevent cisplatin-induced hearing loss.In recent years, domestic and international studies on cisplatin-induced ototoxicity have revealed many new mechanisms and therapeutic targets.Many candidate agents have shown good hearing protection.Moreover, local drug delivery methods are being optimized, promising for further translations to clinical applications.

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplastic disease which is characterized by CD1a + /CD207 + dendritic cell proliferation.LCH can affect multiple systems, and the prevalence of central nervous system involved LCH (CNS-LCH) ranges from 3.4% to 57%.The pathogenesis of CNS-LCH remains unclear.CNS-LCH can be divided into the following: focal mass lesions and lesions associated with neurodegeneration (ND). The clinical manifestations of CNS-LCH vary greatly due to different involved organs.The hypothalamic pituitary-adrenal (HPA) axis is among the most commonly involved site in CNS-LCH with focal mass lesions, and HPA infiltration presents clinically as diabetes insipidus and deficiency of anterior pituitary hormone secretion.LCH-ND is a rare, long-term neurologic complication which can seriously affect patients′life quality.It is mainly characterized by neurological disorders and/or progressive imaging changes.The current standard treatment of CNS-LCH focal mass lesions is based on the Histiocyte Society LCHIII approach, while there is no established optimal therapy for patients who develop LCH-ND.The pathogenesis, clinical manifestations, diagnosis and treatment of CNS-LCH are briefly reviewed in this article in order to provide a reference for clinical diagnosis and treatment.