Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective:To investigate the clinical manifestations, pathological features, treatment and prognosis of primary bone lymphoma in children.Methods:The clinical data of children who were initially diagnosed as primary bone lymphoma and treated in Beijing Children's Hospital Affiliated to Capital Medical University from January 2016 to January 2020 were retrospectively analyzed, including gender, onset age, primary involvement site, clinical stage, pathological type, fracture, and clinical outcome. The related literature was reviewed.Results:All 11 children were initially diagnosed as primary bone lymphoma, with a median age of onset of 8.6 years old (2.7-12.3 years old), including 7 males and 4 females. There were 7 cases of diffuse large B-cell lymphoma (DLBCL), 3 cases of B lymphoblastic lymphoma (BLL), and 1 case of anaplastic large cell lymphoma (ALCL). The initial symptoms were bone pain in 8 cases, local swelling in 1 case, limp in 1 case, and fever in 1 case. One case was in stage Ⅰ, 7 cases were in stageⅡ, and 3 cases were in stage Ⅳ, and the most common sites of involvement were femur and tibia. All 11 cases were treated with chemotherapy according to different pathological types, with a median follow-up time of 45 months (7-80 months). Ten cases got complete remission, 1 case of BLL died of bone marrow recurrence after chemotherapy remission.Conclusions:The clinical manifestations of primary bone lymphoma in children are insidious, DLBCL is the most common pathological type, and the prognosis is good after standardized treatment.

Objective:To explore the clinical features of childhood lymphoma complicated with Pneumocystis jirovecii pneumonia (PJP).Methods:The clinical data, diagnosis and treatment of 5 children with lymphoma complicated with PJP admitted to Beijing Children's Hospital from January 2013 to April 2022 were retrospectively analyzed.Results:Among 5 patients, there were 3 males and 2 females, the median onset age was 7 years old; 4 cases were non-Hodgkin lymphoma and 1 case was Hodgkin lymphoma. Fever and cough occurred 5-18 months after chemotherapy; typical mosaic sign could be seen in 2 cases without pneumothorax and pleural effusion as well as other pathogenic infection; all 5 cases had hypoxemia; 4 cases were diagnosed by next-generation sequencing (NGS). The CD4/CD8 ratio decreased in all cases, and the median CD4 positive T-cell was 200/μl. Trimethoprim-sulfamethoxazole (TMP-SMZ) was irregularly used in 3 cases. During the treatment, all cases received mechanical ventilation, TMP-SMZ intravenously dripping combined with caspofungin, glucocorticoid and gamma globulin. All 5 cases of PJP were cured and there was no recurrent infection.Conclusions:Lymphoma children are susceptible to PJP due to immunocompromise caused by chemotherapy, and their condition progresses rapidly. When encountering fever, shortness of breath, severe lung symptoms and mild signs of children, it is necessary to improve the vigilance of PJP. NGS can help diagnosis, and TMP-SMZ should be actively treated and prevented. Early diagnosis and active treatment can achieve a good prognosis.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Objective:To investigate the efficacy of low-dose uric acid oxidase in treating children with aggressive mature B-cell non-Hodgkin lymphoma accompanied by hyperuricemia.Methods:Clinical data of children with primary aggressive mature B-cell non-Hodgkin lymphoma and hyperuricemia, who were treated in Beijing Children′s Hospital, Capital Medical University from January 2016 to June 2021 were retrospectively analyzed.The serum uric acid concentration was monitored in all pediatric patients from the day before chemotherapy to the seventh day of chemotherapy.Low-dose uric acid oxidase [0.05-0.10 mg/(kg·dose)] was intravenously injected into the patients when the serum uric acid level exceeded the upper limit of the normal range.The therapeutic effect and clinical medication experience of uric acid oxidase were summarized.The change of serum uric acid levels with time before and after the application of different doses of uric acid oxidase was analyzed by a repeated measures ANOVA. Results:A total of 106 children with primary aggressive mature B-cell non-Hodgkin lymphoma and hyperuricemia were enrolled in this study.There were 88 males and 18 females, with a median age of 6.5 (3.5, 10.0) years.The pathological subtypes comprised Burkitt′s lymphoma in 95 cases (89.6%), high-grade B-cell lymphoma in 7 cases (6.6%), and diffuse large B-cell lymphoma in 4 cases (3.8%). Additionally, 39 cases (36.8%) were in clinical stage Ⅲ and 67 cases (63.2%) were in stage Ⅳ.All cases had high tumor burden, including renal involvement in 52 cases (49.1%), tumor lysis syndrome in 42 cases (39.6%), and acute kidney injury in 27 cases (25.5%). Totally, one dose of uric acid oxidase was intravenously injected into 41 children (38.7%), 41 children (38.7%) were given 2 dosages, 20 children (18.9%) were given 3 dosages, and 4 children (3.8%) received 4 dosages.Moreover, 9 cases (8.5%) were supplemented with continuous renal replacement therapy.Serum uric acid concentrations before chemotherapy and 12 hours after injecting the first dose of uric acid oxidase were (741.4±312.9) μmol/L and (210.8±148.6) μmol/L, respectively.The difference was statistically significant ( t=5.288, P<0.001). The change of serum uric acid levels over time before and after the application of different doses of uric acid oxidase in children was compared, and no significant difference was found ( F=0.225, P=0.879). No delay in chemotherapy or death arising from tumor lysis syndrome and acute kidney injury occurred within 28 days after chemotherapy. Conclusions:Low-dose and on-demand application of uric acid oxidase can rapidly and effectively reduce serum uric acid levels in children with aggressive mature B-cell non-Hodgkin lymphoma in the early stage of chemotherapy.

Objective:To explore the efficacy of anti-programmed cell death protein 1 (PD-1) antibody for children with refractory or relapsed Hodgkin lymphoma.Methods:Clinical data including short-term efficacy, long-term efficacy and adverse reaction of Hodgkin lymphoma children treated with anti-PD-1 antibody in Beijing Children′s Hospital, Capital Medical University from December 2017 to June 2021 were analyzed retrospectively. Efficacy was evaluated as complete remission (CR), partial remission (PR), stable disease (SD), progressed disease (PD) and no response.Results:A total of 6 cases were included, including 5 males and 1 female. The age at the start of anti-PD-1 antibody treatment was 11.6 (10.2, 13.3) years, including 3 cases of mixed cellularity type, 2 cases of nodular sclerosis type, and 1 case of nodular lymphocyte-predominant type. There were 4 cases of stage Ⅳ and 2 cases of stage Ⅲ. All cases were assigned to the high-risk group, and 5 cases had B symptoms, all cases were refractory or relapsed Hodgkin lymphoma before the start of anti-PD-1 antibody treatment. Early evaluation showed that within 12 weeks of the treatment, 3 cases achieved PR and 3 cases achieved SD, while late evaluation showed that after 16 weeks of the treatment, 5 cases achieved CR and 1 case achieved PR. None of the children progressed during treatment. The follow-up time was 27 (21,41) months. Among all cases, 5 cases had event-free survival and sustained remission, 1 case had fever about 4 weeks after the drug withdrawal, finally he was confirmed to be transformed to B cell lymphoma between diffuse B cells and classic Hodgkin lymphoma. All the patients were well tolerated with anti-PD-1 antibody therapy. No adverse reactions such as high fever, chills, rash, etc. were observed during infusion. None of the patients were delayed, dose reduction or withdrawal due to adverse reactions. Two cases had reactive skin vascular hyperplasia during the treatment, without pain or itching, and they recovered on their own after stopping anti-PD-1 antibody therapy without other special treatment.Conclusion:Anti-PD-1 monoclonal antibody for children with refractory or relapsed Hodgkin lymphoma have good efficacy and tolerable side effects.

Objective:To analyze the clinicopathological features, treatment and prognosis of Epstein -Barr virus(EBV) positive diffuse large B cell lymphoma(DLBCL) in children, so as to improve the knowledge of pediatricians on this disease.Methods:The data of 6 cases of EBV positive DLBCL who were initially diagnosed and regularly treated in Beijing Children′s Hospital from January 2016 to December 2019 were collected, including basic information (gender, age, first symptom, and course of disease), pathological results [immunohistochemistry, EBV encoded RNA(EBER), latent membrane protein(LMP), and C- MYC gene], immune function, EBV index, treatment group, treatment plan and prognosis. Results:There were 4 males and 2 females, with the average age of 6.67 years.The uric acid was 266.2 μmol/L, lactic dehydrogenase(LDH) was 346.5 U/L at early stage, and 1 patient had immunodeficiency.The immune function test before chemotherapy indicated that the proportion of auxiliary T cells decreased in 4 cases, and the humoral immune function was normal in all patients.There was no evidence of recent infection in 6 patients, and EBV-DNA increased in 3 patients.There were 2 cases of stage Ⅲ, 4 cases of stage Ⅳ, 1 case of giant tumor, 2 cases of symptom B, 6 cases of extranodal invasion, 4 cases of central invasion and 1 case of bone marrow invasion.Three patients died and three survived.Immunohistochemistry showed that: (1) CD 19, CD 20, and CD 79a were expressed in all patients, and CD 30 was expressed in 5 patients.(2) C- MYC gene was detected by immunofluorescence in situ hybridization method in all patients, and no MYC break, Bcl-2 and Bcl-6 break and amplification were found.(3) EBV: EBER and LMP-1 were expressed in all patients. Conclusions:The pathological changes of EBV positive DLBCL are similar to those adults.The origin of non-germinal center and extranodal and central invasion are more common.The prognosis of the patients with central nervous system invasion is very poor, and the recurrence and progress of the disease often occur in the treatment or in the early stage of drug withdrawal.At present, there is no effective and feasible treatment plan.It is suggested that the patients in the late stage should receive allogeneic hematopoietic stem cell transplantation as soon as possible after intensive treatment, so as to improve the survival rate.

Objective:To explore the risk factors for misdiagnosis of ruptured intracranial aneurysm.Methods:A total of 606 patients with ruptured intracranial aneurysms, admitted to our hospital from October 2014 to October 2020, were enrolled in our study; these patients were divided into two groups according to whether they were initially misdiagnosed: misdiagnosis group ( n=35) and non-misdiagnosis group ( n=571). The general clinical data of patients from the two groups were compared; multivariate Logistic regression was used to identify the independent influencing factors for misdiagnosis. Receiver operating characteristic (ROC) curve was drawn according to the regression model to evaluate the predictive value of different factors for misdiagnosis. The re-rupture of aneurysms and different prognoses were compared between the two groups. Results:There were significant differences in Fisher grading, primarily visited departments, aneurysm diameters, hospital levels, and propaganda and education situation of the first visited doctors between the 2 groups ( P<0.05). Multivariate Logistic regression analysis showed that the independent factors for misdiagnosis of ruptured intracranial aneurysms were as follows: modified Fisher grading 0-II ( OR=12.284, 95%CI: 5.397-27.958, P=0.000); aneurysm diameter ≥10 mm ( OR=2.871, 95%CI: 1.276-6.456, P=0.011), not neurology or neurosurgery as primarily visited departments ( OR=9.279, 95%CI: 4.019-21.420, P=0.001), and first visited doctor not receiving propaganda and education ( OR=2.907, 95%CI: 1.258-6.721, P=0.013); area under the ROC curve of not neurology or neurosurgery as primarily visited departments and modified Fisher grading 0-II were 0.747 and 0.754, which had good predictive value in the misdiagnosis of ruptured intracranial aneurysm. Re-ruptured aneurysms occurred in 37.1% patients from the misdiagnosis group and 5.3% patients from the non-misdiagnosis group, with significant difference ( P<0.05); and the proportion of patients with poor prognosis at discharge (modified Rankin scale scores>2) was 42.9% in the misdiagnosis group and 22.6% in the non-misdiagnosis group, with significant difference ( P<0.05). Conclusion:Patients with modified Fisher grading 0-II, without neurology or neurosurgery as primarily visited departments and with aneurysm≥ 10 mm, and patients whose first visited doctor not receiving professional education of spontaneous subarachnoid hemorrhage have high risks of misdiagnosis of ruptured intracranial aneurysm; strengthening the professional education of spontaneous subarachnoid hemorrhage for doctors from non-neurology or neurosurgery departments of hospital at different levels may reduce the misdiagnosis rate.

Objective:To investigate the influencing factors for unfavorable outcome of low-grade aneurysmal subarachnoid hemorrhage (aSAH).Methods:A retrospective study was performed. The clinical data of 273 patients with aSAH of World Federation of Neurosurgery (WNFS) grading I and II, admitted to our hospital from April 2017 to March 2021, were collected. According to modified Rankin scale (mRS) scores 3 months after treatment, these patients were divided into favorable outcome group (mRS scores of 0-2) and unfavorable outcome group (mRS scores of 3-6). Statistical methods were used to analyze the clinical and imaging data differences between the two groups and identify the independent influencing factors for unfavorable outcome. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive values of different independent factors in unfavorable outcome.Results:Among the 273 patients with low-grade aSAH, 45 patients had unfavorable outcome and 228 patients had favorable outcome. Univariate analysis showed that there was significant difference between the 2 groups in age, Fisher grading distribution, proportions of patients complicated with shunt dependent hydrocephalus, with delayed cerebral ischemia, or with intracranial hemorrhage, and WNFS grading ( P<0.05). Multivariate Logistic regression analysis showed that concurrent shunt dependent hydrocephalus ( OR=5.075, 95%CI: 1.705-15.102, P=0.004), age ( OR=1.090, 95%CI: 1.036-1.147, P=0.004), delayed cerebral ischemia ( OR=8.282, 95%CI: 3.447-19.896, P=0.000), and postoperative intracranial hemorrhage ( OR=8.603, 95%CI: 2.332-31.745, P=0.001) were independent influencing factors for unfavorable outcome. ROC curve analysis showed that the optimal diagnostic threshold of age was 65 years, and the areas under ROC curve for delayed cerebral ischemia and age in predicting unfavorable outcome were 0.733 ( 95%CI: 0.653-0.813, P=0.000) and 0.709 ( 95%CI: 0.622-0.796, P=0.000). Conclusion:Low-grade aSAH patients with age≥65, postoperative shunt dependent hydrocephalus, delayed cerebral ischemia, and intracranial hemorrhage are more likely to have unfavorable outcome; age and complicated delayed cerebral ischemia have certain diagnostic value in low-grade aSAH patients.