Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

Objective:To assess the preliminary efficacy and safety of modified Société Internationale d′Oncologie Pédiatrique Epithelial Liver Tumor Study Group (SIOPEL)-4 protocol for pediatric hepatoblastoma (HB) with lung metastases.Methods:This prospective cohort study enrolled 27 newly diagnosed pediatric HB with lung metastases who received the modified SIOPEL-4 protocol at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children′s Hospital between January 2020 to December 2023. Clinical characteristics, lung response rates to induction chemotherapy, treatment outcomes, prognostic factors and sever chemotherapy toxicities at different stages were analyzed. Survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by Log-Rank test.Results:Of the 27 patients, there were 17 males and 10 females, with the age of 21 (15, 33) months. During the follow-up of 31 (12, 45) months for 17 continuous complete remission patients, 4 cases disease progression (2 cases death) and 6 cases relapse were observed. The 2-year event free survival (EFS) and overall survival (OS) rate was (58±11)% and (89±7)%, respectively. All the 27 patients had response to block 1-3 induction chemotherapy (cisplatin+doxorubicin), with 14 cases (52%) achieving complete response and 13 cases (48%) achieving partial response of lung metastatic lesions, the 2-year EFS rate was (81±12)% and (34±14)%, respectively ( χ 2=6.76, P=0.009), the 2-year OS rate was 100% and (79±13)%, respectively ( χ2=2.12, P=0.145). Patients with caudate lobe tumors or ≥10 pulmonary metastatic nodules had significantly lower EFS rates ( χ2=5.36, 7.84, P=0.021, 0.005, respectively). The incidence of grade 3/4 neutropenia after block 1-3 induction chemotherapy, CD (carboplatin+doxorubicin), and VI (vincristine+irinotecan) consolidation chemotherapy was 90% (73/81), 75% (58/77), and 31% (11/35), respectively. The incidence of grade 3/4 thrombocytopenia was 77% (62/81), 69% (53/77), and 14% (5/35), respectively. The incidence of grade 3/4 infections was 64% (52/81), 25% (19/77), and 20% (7/35), respectively. The differences between the groups were statistically significant ( χ2=43.51, 42.69, 33.00, all P<0.001). Two patients (10%) of the 20 evaluable patients for ototoxicity occurred grade 3 and higher hearing impairment, with 1 patient requiring a hearing aid. Conclusions:The modified SIOPEL-4 regimen shows good preliminary efficacy and safety in treating pediatric HB with lung metastases. The prognosis for patients with residual lesions in the lungs after induction chemotherapy needs to be improved. Attention should be given to the ototoxicity induced by high-dose cisplatin chemotherapy.

Objective:To investigate the efficacy and safety of targeted therapy with Crizotinib for children with ALK gene mutation positive inflammatory myofibroblastic tumor (IMT). Methods:A retrospective analysis was performed on 4 children with ALK gene mutation positive IMT admitted to Shanghai Children′s Hospital from January 2019 to June 2021.Among them, 3 cases were given the targeted drug Crizotinib[280 mg/(m 2· time), q12h] orally, and 1 case was observed after complete tumor resection to analyze the efficacy and adverse drug reactions. Results:All 4 cases were male, aged from 2 years and 3 months to 11 years and 3 months.The tumors originated from the abdominal cavity in 2 cases, the right orbit in 1 case, and the right lung in 1 case.Pathological immunohistochemistry and fluorescence in situ hybridization were both positive for ALK gene mutation, and complete remission was achieved after comprehensive treatment.Among them, 3 patients were treated with oral Crizotinib, and 2 patients were tried to stop taking the drug for 1 year, relapsed 1 month later, and still achieved complete remission after the second treatment.The 4 cases were followed up for 8-30 months, and all survived.All the cases showed no abnormalities in blood image, liver and kidney function, myocardial enzyme profile, cardiac function, hearing and vision, and 2 cases showed prolonged Q-T interval in the course of Crizotinib treatment, which could be recovered by temporary withdrawal of drug, and no abnormality in electrocardiogram was found in continued drug use. Conclusions:Crizotinib was used to treat ALK mutation positive IMT, shrink tumor and consolidate postoperative treatment, which is a good choice for IMT in children with difficult surgical resection and refractory recurrence.

Objective To analyze the clinical data of children with Langerhans cell histiocytosis (LCH),to discuss the therapeutic effect,and to analyze the factors related to prognosis.Methods A total of 45 children diagnosed as LCH were divided into group A (18 cases with bone lesion only),group B(6 cases with soft tissue lesion),and group C (21 cases with viscera lesion) according to Shanghai Children's Hospital-LCH-2007 scheme [SCH-LCH-2007 (modified DAL-HX83/90) scheme].(1) Initial treatment:group A was treated with Prednisone (Pred) + Vincristine (VCR) for 28 weeks,and group B was treated with Pred + VCR + Etoposide (VP16) + Mercaptopurine (6MP) for 43 weeks,and group C was treated with Pred + VCR + VP16 + Methotrexate (MTX) +6MP for 52 weeks.(2) Re-treatment scheme after relapse included:①upgrading treatment,group A to group B,group B to group C.②Individual treatment for group C included VP16 modification,and maintained Thymosin and/or Ciclosporin etc.Results The total survival rate was 93.3％ (42/45 cases) and recurrence rate was 26.7％ (12/45 cases).Children in group A and B were all effective,while 2 patients in group C died,and 1 case missed follow-up.Multi-factor analysis showed that the factors like age,sex,group,skeleton,soft tissue,erythra,lymph gland,lung,mouth,ears,hypophysis pituitary had no statistical significance,but liver,spleen and blood involvement had statistical significance in disease relapse:liver (P=0.007 1),spleen (P=0.016 9),and blood (P=0.011 1).Conclusion LCH can affect several organs of children and relapse,and modified DAL-HX83/90 scheme is very effective.The liver,spleen and hematopoiesis system involvement is correlates with the relapse.

Objective Previous study found that ifbroblast growth factor-2(FGF2) expression was at a low level in bone marrow of children with aplastic anemia. In this study, we established a bone marrow failure animal model to investigate whether FGF2 is involved in bone marrow failure. Methods BALB/c mice were irradiated by 5.0 Gy ray, and then infused with 1×106 lymphocytes from allogeneic mice lymph node. Peripheral blood cells and bone marrow mononuclear cells counting and bone marrow pathology were done. FGF2 protein in bone marrow mononuclear cells was measured by ELISA. Results Compared with the control group, the counting of hemoglobin, white blood cell, platelet and bone marrow mononuclear cell in aplastic anemia mouse model were signiifcantly deceased (P<0.05). Moreover, FGF2 expression in aplastic anemia mouse model were signiifcantly reduced (P<0.05). Conclusions 5.0 Gy ray irradiation and then 1×106 lymphocyte infusion in mice can induce bone marrow failure similar to the features of aplastic anemia. The low expression of FGF2 in bone marrow of aplastic anemia patients may play an important role in the pathogenesis of aplastic anemia.