OBJECTIVE:To explore the distribution patterns of Traditional Chinese Medicine(TCM)syndromes in children with lymphoma-related cancer-related fatigue(CRF)using latent structure model analysis. METHODS:This was a single-center cross-sectional study in which Chinese medicine diagnostic information was collected from 153 children diagnosed with childhood lymphoma CRF from July 2022 to December 2023.The latent structure model of the CRF for childhood lymphoma was constructed using the latent tree model-extension adjustment simplification until termination algorithm,and the population was classified using comprehensive clustering.Combined with the existing guidelines,we explored the distribution characteristics and dynamic progression of syndrome types in patients with childhood lymphoma CRF. RESULTS:Initially,a latent structural model incorporating 72 manifest variables was constructed.Through comprehensive clustering,6 distinct TCM syndrome types were identified,and corresponding quantitative identification rules were formulated.The 153 pediatric cases were then reclassified according to these rules,with the syndromes ranked in descending order of percentage as follows:blood deficiency and stasis,vigorous fire due to Yin deficiency,deficiency of both the lung and spleen,liver constraint and Qi stagnation,dampness-heat retention,and heart-spleen heat accumulation.Preliminary findings suggest that the shifting patterns of TCM syndromes in childhood lymphoma CRF may exhibit clinically meaningful relationships with tumor staging and treatment time courses. CONCLUSION:Using latent structure analysis,6 TCM syndromes and their quantitative identification rules were identified.A comparison with existing guidelines revealed that CRF in patients with childhood lymphoma is characterized primarily by a syndrome of mixed deficiency and excess.Therefore,in the treatment of pediatric CRF,it is recommended not only that deficiency patterns be addressed but also that the clinical stage and treatment phase of the tumor be considered.Additionally,therapeutic strategies should emphasize promoting digestion,resolving food stagnation,regulating Qi,and clearing heat to formulate a tailored treatment plan.

Low triiodothyronine (T3) syndrome, also known as non-thyroidal illness syndrome (NTIS), was one of the common endocrinopathies in critical illness. The potential impacts of low T3 syndrome on survival, endocrine function, and nutritional status of patients with aggressive mature B-cell non-Hodgkin lymphoma (NHL) needed to be explored. We enrolled 225 patients. T3 levels were captured when starting chemotherapy, finishing chemotherapy, and at the first follow-up visit from 6 months after chemotherapy. Latest ultrasound results were recorded. Kaplan-Meier curves were used to compare overall survival (OS) or progression-free survival (PFS). We performed Cox's proportional hazards regression model to analyze prognostic factors of OS and PFS. Ultrasound abnormality and weight gain were tested with the χ2 test. The percentage of patients with low T3 syndrome decreased from 55.1% (124 out of 225) to 2.0% (4 out of 201), then further dropped down to 0 (0 out of 173). With a median follow-up of 32.9 months, low T3 syndrome was identified as a statistically significant factor affecting both OS (p = .047; hazard ratio [HR] = 8.18, 95% CI: 1.03-64.97) and PFS (p = .049; HR = 4.64, 95% CI: 1.01-21.31) in multivariate analysis. No significant effects of low T3 syndrome on abnormal thyroid ultrasound results and weight gain were found. In conclusion, low T3 syndrome has a high incidence in pediatric patients with aggressive mature B-cell NHL, and low T3 syndrome has a significant impact on long-term survival. It appears transient and could not contribute to impaired thyroid function.

Objective：To analyze the clinical features of central nervous system involvement (CNS3) in pediatric anaplastic large cell lymphoma (ALCL) and evaluate the efficacy of CNCL-ALCL-2017 protocol for the treatment of CNS3. Methods：The clinical data of 215 pediatric ALCL patients ≤18 years old enrolled in the Chinese Children's Cancer Group (CNCL) between April 2017 and March 2023 were collected sequentially. All enrolled patients staging and CNS layering were according to the IPNHLSS staging system and treated with CNCL-ALCL-2017 protocol (modified BFM-ALCL99 protocol). The clinical features at diagnosis and treatment outcomes of CNS3 patients were analyzed. All patients were followed up until June 30, 2023. Data were collected using a unified information platform. Associations between patient characteristics were analyzed with Chi-squared or Fisher's exact tests. Eventfree survival (EFS) and overall survival (OS) curves were estimated according to the KaplanMeier method and compared by Logrank test. Furthermore, statistical analysis was performed using SPSS 22.0 software. P<0.05 was considered statistically significant. Results: Among the 215 ALCL pediatric patients, 17 (7.9%) had CNS3, including 13 males and 4 females with median age of 8.0 (range 1.0-14.0) years. In this patients, brain parenchyma and spinal cord involvement were found in 58.8% (10/17) patients on imaging, with space-occupying lesions in 7 cases and abnormal signals on MRI in 4 cases. Concurrent space-occupying lesions and abnormal signals on MRI was detected in 1 case. Cerebrospinal fluid (CSF) positivity was detected in 35.3% (6/17) patients, including 2 cases with positive ALK gene and 5 cases with positive flow cytometry, with 1 case positive for both. Cranial nerve deficits such as facial nerve palsy, visual or hearing impairment were observed in 23.5% (4/17) patients. Concurrent CSF, imaging and cranial nerve abnormalities were present in 5.9% (1/17), while two of this were present in 29.4% (5/17). Isolated CSF positivity without other abnormalities was detected in 23.5% (4/17). Pathological subtypes included common type (76.5%, 13/17), histiocyte-rich variant (5.9%, 1/17), small cell variant (5.9%, 1/17), others (11.8%, 2/17). Immunohistochemistry showed ALK + in 94.1% (16/17) and CD3 + in 76.5% (13/17). Concurrent ALK gene positivity in both peripheral blood and bone marrow was detected in 64.7% (11/17), with 58.8% (10/17) positive in both samples. The median follow-up of all patients was 35.4 months (range 0.5-74.9). All CNS3 patients had stage IV disease and were treated with regimen D (with 5 g/m 2 methotrexate). The 3-year OS was 94.3%, 98.2% and 93.3% for CNS1 (144, 67.0%), CNS2 (54, 25.1%) and CNS3 (17, 7.9%) patients, respectively; the 3-year EFS was 85.6%, 90.3% and 86.7%, respectively. No significant differences were found among the three groups. The 3-year OS and EFS for the whole cohort were 95.1% and 84.7%, respectively, also with no significant differences from the CNS3 group. Of the CNS3 patients, 1 was lost to follow-up after the first course, 1 died during treatment, and the interim CR rate was 75.0% (12/16). CSF conversion was achieved in 3/6 (50%) CSF-positive patients. 6.25% (1/16) patient had CSF ALK gene re-positivity during maintenance and persistent positivity despite additional ALK inhibitor alectinib and intrathecal therapy. In the CNS1 group, 2 cases were lost to follow-up and 4 cases died. The relapse rate was 11.4% (16/140), and the rate of central nervous system relapse was 2.1% (3/140). Additionally, the rate of CNS1 relapse was slightly higher but not statistically significantly different for CNS2. Conclusions: CNS involvement is relatively rare in pediatric ALCL. Detection rate of CNS3 can be improved by CSF flow cytometry and gene screening. The prognosis of CNS3 was significantly improved with CNCL-ALCL-2017 protocol, which may be related to the increased dose of methotrexate in the protocol. The short follow-up time and the small number of cases in this group may affect the results. Furthermore, CNS relapse rate of CNS2 was not markedly higher compared to CNS1. Keywords: Anaplastic large cell lymphoma; Pediatric; Central nervous system; Clinical features; Prognosis

Isolated central nervous system (CNS) involvement due to posttransplantation proliferative disorder (PTLD) is even rarer, with only a few cases reported in the literature. CNS involvement in patients with mature B-cell non-Hodgkin's (NHL) and PTLD confers a significantly worse prognosis as compared to patients without CNS lymphoma disease. Treatment of CNS lymphoma (CNSL) is challenging due to resistance to conventional cytotoxic and intrathecal chemotherapy. Here, we report the successful use of intrathecal rituximab in two pediatric cases of CD20 + isolated CNSL that had failed to respond to standard chemotherapy, intravenous rituximab and Epstein-Barr virus (EBV)-specific cellular therapy. However, after repeated intrathecal administration of rituximab, both patients’ clinical symptoms were alleviated, which has created opportunities for further treatments. We emphasise that intrathecal rituximab may be a safe and promising strategy for the treatment of pediatric patients with CD20 + isolated CNSL. The literature on this topic was also reviewed.

Objective: To investigate the clinical-pathology characteristics, risk factors, necessary for VBL maintenance therapy，through summarize the clinical data of 221 cases of pediatric Anaplastic Large Cell Lymphoma (ALCL), treated with CNCL-ALCL-2017 witch is modify from BFM-ALCL-99 (±vincristine maintenance therapy) in China Net Childhood Lymphoma (CNCL). Methods: Data were collected on 221 children with ALCL enrolled from CNCL at time between April 2017 to March 2023, including: numbers of cases enrolled in each single center, gender and age at the time of initial diagnosis, the first initial symptom, a delay diagnosis, the misdiagnosis disease , the site of involvement, the level of blood uric acid, the level of blood lactate dehydrogenase, the bone marrow and CNS status, tumor complication, complicated with HLH, staging and treatment subgroups, pathological subtypes, CD3 expression in tumor tissue, bone marrow and peripheral blood ALK gene expression at initial diagnosis (qPCR + FISH), and treatment outcomes, treatment strategy(vincristine maintenance or not), time from initial diagnose to relapse, second-line treatment regimen after relapse, and treatment outcomes after relapsed. Statistical analysis was conducted using SPSS 21.0 software. Results: 221 cases were from 22 hospitals in China. Male = 144 cases, female = 71 cases, age range from 1-16 years (median age 8.9 years), duration from initial symptoms onset to diagnosis was 0.3-11 months (median time 1.0 months), delayed diagnosis was present in 51(23%) children (45 children were misdiagnosed with infectious diseases). Pathological subtypes were: common sub type = 150(67.8%), small cell sub type = 19(8.5%), histiocytic variant subtype = 9(4%), ALK negative subtype = 12(5.4%).others = 31(14%). CD3 expression in tumor: negative = 119, positive = 91. ALK positive by qPCR in peripheral blood at the time of the initial diagnosis = 77, ALK positive by qPCR in bone marrow = 78, bulky disease= 21, mediastinal invasion = 84, CNS invasion = 17, skin invasion = 32. tumor related HLH = 25, normal LDH level at initial diagnosis = 133, 1-fold elevated = 45, 2-3-fold elevated = 39, 4-fold elevated = 2, >4-fold elevated = 2, stage I = 5, stage II = 24, stage III = 70, stage IV = 120 , leukemic stage = 2 . Grouping: group A = 1, group B = 21, group C = 191, group D = 8. Vincristine maintenance = 121. Median follow-up time was 35.4 months (0.5-74.9 months), OS at 3 years = 95.1±1.5% (95% CI = 90%-97.3%, Fig. 1), EFS at 3 years = 84.7±4.5% (95% CI = 79%-89.9%, Fig. 2), and there were a total of 23 patients with events, median time was7 months. There were 10 patients died, 5 of them quit to the treatment, median time was 5 months, and 13 patients who had an event but still alive after second line treatment. Univariate results of the 3 years EFS are detailed in Table 1, with statistically significant including (<0.05): tumor related HLH before treatment, LDH levels higher than 4 times normal and MDD positive at the beginning of the disease, and treated without VBL. The event patients are 23 cases ,the detailed in Table 2, which showed that the earlier the event occurs, the higher the mortality rate. Conclusion:Pediatric ALCL in China is mostly found in school-age boys, and it is easy to be diagnosed as infectious diseases at the time of initial diagnosis due to high fever and elevated CRP. 87% of patients were diagnosed as late stage or high-risk group. The application of the CNCL-ALCL-2017 protocol showed a 3-year OS 84.7% and 3-year EFS 95.1%, indicating that the efficacy was significantly better than that of various centers before the multi center cooperation. The overall survival time is significantly better than the event free survival time, indicating that most patients with progression and recurrence still have a chance of re remission after second line treatment. Adverse prognostic factors include a significant increase in LDH levels at initial diagnosis, initial onset of HLH, positive MDD before treatment, and no use of vinblastine maintenance therapy. Recurrent children: The median recurrence time is 7 months, and the prognosis of early progression and recurrence is worse than that of late recurrence. Key words: Anaplastic large cell lymphoma, Pediatric, Clinical-pathology features, Prognosis

C-MYC rearrangement has been listed as a new subcategory of B-cell acute lymphoblastic leukemia (B-ALL) in the latest International Consensus Classification (ICC), but B-cell lymphoblastic lymphoma (B-LBL) with C-MYC rearrangement is extremely rare and therefore is a novel finding worth reporting. In this study, we described a small number of pediatric cases of B-LBL with C-MYC rearrangement, which overlapped features of B-LBL and Burkitt lymphoma (BL), including highly aggressive clinical presentation, lymphoblasts with precursor B-cell phenotype and C-MYC rearrangement; the combination treatment of the mature B-NHL protocol and ALL-type protocol may be appropriate for this rare entity, and more studies are required to identify an adequate therapeutic strategy.

PURPOSE:Non-NPM1-ALK fusions in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALK+ ALCL) are rare and insufficiently characterized in Chinese populations. This study analyzed the clinical features, treatment responses, and potential prognostic implications of these variants. METHODS:In this retrospective study, eight pediatric patients with ALK+ ALCL and non-NPM1-ALK fusions were diagnosed between April 2017 and April 2025. For prognostic comparison, a cohort of 107 newly diagnosed patients with NPM1-ALK fusions was used. Clinical data, treatment courses, and outcomes were reviewed. Event-free survival (EFS) was estimated using the Kaplan-Meier method. RESULTS:Among 128 ALK+ ALCL patients, 8 (6.3%) had non-NPM1-ALK fusions (TPM3, n = 3; ATIC, n = 2; CLTC, MYH9, TRAF1, n = 1 each). At a median follow-up of 17.5 months (range, 1.2-97.9), all patients were alive. Analysis of patients with non-NPM1-ALK fusions (n = 7, newly diagnosed) indicated a trend toward inferior 5-year EFS compared with the NPM1-ALK group. Within the non-NPM1-ALK cohort, no events were observed in the three patients TPM3-ALK fusions, while four patients with other fusion types experienced relapse or disease progression. ALK inhibitors (crizotinib/alectinib) were associated with sustained remission in three patients with relapsed/refractory disease. CONCLUSION:Pediatric ALK+ ALCL with non-NPM1-ALK fusions exhibits diverse clinical features and outcomes. TPM3-ALK fusions might correlate with a more favorable course, while other variants may face a potentially higher relapse risk. ALK inhibitors showed promising efficacy in the salvage setting. These preliminary findings highlight the need for larger prospective studies to validate mutation-specific risk stratification and therapeutic strategies.

BackgroundT-cell lymphoblastic lymphoma (T-LBL) is the second most common subtype of non-Hodgkin's lymphoma (NHL) in children and adolescents. Under current treatment, the event-free survival rate (EFS) is between 75% and 85%. The unified CNCL-LBL-2017 protocol was adopted for treatment in the China-Net Childhood Lymphoma Group（CNCL）in order to standardize the diagnosis and treatment of childhood lymphoma, and improve the prognosis. This study aimed to analyze the clinical features of pediatric T-LBL and evaluate the theraputic efficacy, explore the prognostic factors. Methods From May 2017 to June 2023, 548 newly diagnosed T-LBL patients aged ≤18 years from 29 centers in CNCL were enrolled in this study. According to clinical stage, prognostic genes and treatment response, the children were divided into low, intermediate and high risk groups, and stratified treatment was performed according to CNCL-LBL-2017 protocol modified from LBL-BFM95 trial, with follow-up until December 31, 2024. The therapies aimed at central nervous system (CNS), Cranial irradiation was omitted even for the patients with CNS involvement at the diagnosis. All patients received triple intrathecal injections, with stratified treatment based on CNS status. Patients with CNS2/CNS3 received more intrathecal injections. Results A total of 548 patients were included. The median age of disease diagnosis was 8.0 years (range:1.0-16.0 years. There were 413 (75.4%) males and 135 (24.6%) females. The disease course of 434 patients(79.2%) was less than 30 days. Clinical staging: 1 case(0.2%) in stage Ⅰ, 3 cases(0.5%) in stage Ⅱ , 153 cases (27.9%) cases in stage Ⅲ and 391 cases(71.3%) in stage Ⅳ. 426 cases（77.7%）presented with anterior mediastinal mass, 386（70.4%）bone marrow involvement, 54（9.9%）CNS involvement. Median serum LDH value was 632 IU/L (range 108-35,645); 198 patients(36.1%) had a LDH value more than 1,000 IU/L.148 cases (27.0%) of the children had symptoms of airway obstruction at diagnosis, and 137 cases (25.0%) were accompanied by superior vena cava syndrome (SVCS). 49 cases (8.9%) were complicated with tumor lysis syndrome (TLS) during prednisone pretreatment. There were 1 case (0.2%), 164 cases (29.9%), and 383 cases (69.9%) in the low, intermediate, and high-risk groups, respectively. The follow-up time was 44.5 (0.8, 93.9) months. The 5-year EFS rates and 5-year overall survival(OS) were 77.1±1.9% and 84.2±1.6%, respectively. The 5-year EFS rates of low, intermediate and high risk groups were 100.0%, 77.6±3.3% and 77.6±2.3%, respectively. Recurrence/progression occurred in 98 cases (31 BM relapses, 18 CNS, 25 primary sites, 2 testicular, 22 multisystem recurrence), recurrence rate 17.9%, and the recurrence time was 11.5 (2.1, 75.6) months, in which 72 cases died and 26 cases survived. The recurrence rate of CNS is 3.3%. All patients experienced grade 3-4 hematological toxicity. Infection-related death occurred in 21 cases (3.8%). Eighty-four patients with high-risk factors or relapsed/refractory conditions received allogeneic hematopoietic stem cell transplantation in this study. Based on Cox regression analysis, the failure to achieve complete remission at the end of induction (mid-term evaluation) (HR=8.528, 95%CI: 2.832-25.237, P=0.001) was the only risk factors for EFS rate. Conclusion T-LBL in childhood and adolescence is highly aggressive and liable to relapse in the early stage of treatment. CNCL-2017-LBL protocol got a certain efficacy close to the results of international studies. High-intensity chemotherapy has improved the therapeutic effect for patients in the high-risk group. CNS relapse incidence rate didn't increase without cranial irradiation.

Studies have confirmed that rituximab (RTX) can improve the efficacy of BL, but there is a certain effect on the level of immunoglobulin, which will lead to the verification of infection, and the previous study of our center has confirmed that reducing the dose of RTX (4 doses) can achieve a similar effect to the standard dose of RTX (6 doses), can it reduce the effect on the level of immunoglobulin? To date, few studies have concentrated on the effects of immunoglobulin (Ig) on Chinese paediatric patients. This study aimed to examine whether there is a variation in the impact of different doses of RTX on immunoglobulin levels in the high-risk group of children with BL. Clinical data of high-risk pediatric patients with BL who were treated in Beijing Children’s Hospital (Beijing, China) were retrospectively analysed. Baseline characteristics and serum Ig levels were collected at four distinct time points (t0 = pre-chemotherapy, t1 = at the end of chemotherapy, t2 = 6 months post-chemotherapy, t3 = 12 months post-chemotherapy). Ig levels were measured at various time points before and after treatment within three RTX treatment groups: R0 group (standard chemotherapy without RTX), R6 group (6 doses of RTX + chemotherapy), and R4 group (4 doses of RTX + chemotherapy). The objective was to compare whether differences existed among the three groups. The results revealed that the study enrolled 300 high-risk BL patients, including 256 boys and 44 girls, distributed across three groups based on RTX dosage: R0 group (n = 38), R6 group (n = 87), and R4 group (n = 175). Median Ig levels were assessed at four time points (t0, t1, t2, t3) for each group. In the R0 group, IgA and IgM levels significantly decreased at t1 compared with t0 (P = 0.006 and 0.002, respectively), while were gradually recovered at t2, returning to t0 levels at t3 (P = 0.073 and 0.293, respectively). IgG levels exhibited no significant difference between t0 and t1 (P = 0.89), reaching their lowest levels at t2 and returning to t0 levels at t3 (P = 0.14). In the R4 group, the minimum levels of IgA, IgM, and IgG were identified at t1 (P < 0.001, < 0.001, and < 0.001, respectively), which were gradually recovered at t2, while remained lower than t0 levels at t3 (P < 0.001, < 0.001, and = 0.005, respectively). The R6 group exhibited reduction in IgA and IgM levels at t1, with gradual recovery at t2 and t3, while remained lower than t0 levels (P = 0.003 and < 0.001, respectively). IgG levels in the R6 group decreased at t1 (P < 0.001) and did not return to t0 levels at t3 (P = 0.004). In the R4 and R6 groups, it was observed that children with hypogammaglobulinemia pre-RTX were more likely to combine with persistent hypogammaglobulinemia (PH-Ig) post-RTX. A 1:1 matched comparison between R4 and R6 groups (78 patients each) revealed consistently higher IgA, IgM, and IgG levels in the R4 group at each time point after chemotherapy. Notably, IgA and IgG levels recovered earlier in the R4 group than those in the R6 group (P < 0.05). Burkitt lymphoma in the high-risk group were more likely to complicated hypoimmunoglobulinemia after treatment, it is important to monitor Ig levels before and during treatment, and to inform replacement therapy for Ig. Compared with standard chemotherapy group, the RTX group had a longer time of low Ig and a slower recovery, reducing the dosage of rituximab can improve the recovery of IgA and IgG levels.

OBJECTIVE:To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD:From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS:A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION:The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Click to increase image sizeClick to decrease image size AcknowledgmentsWe thank the medical staffs of Hematology Center, Beijing Children’s Hospital, Capital Medical University, and all participated patients and their families.Authors’ contributionsDYL and GHX participated in study design and data interpretation. The manuscript was prepared by GHX, and DYL was a major contributor to review and edit the manuscript. ZCJ is responsible for tissue examination and diagnosis. JL and YJ participated in the statistical analysis and table production. ZNN is responsible for imaging diagnosis. HS, ZM, and YXL were responsible for the collection of clinical specimens and pathological data. ZYH and WTY were responsible for study design and supervision. All authors read and approved the final manuscript. All authors read and approved the final manuscript.Ethical approval and consent to participateThis study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (IRB) of Beijing Children’s Hospital, Capital Medical University. All parents signed informed consent forms.Disclosure statementNo potential conflict of interest was reported by the author(s).Informed consentwas obtained from all subjects or their legal guardian(s)/parents (for children’s below 16 years old). This study is accordance with the relevant guidelines and regulation.Consent for publicationNot applicable.Data availability statementRaw data are available from the corresponding author upon reasonable request.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.

目的 探讨全程营养管理在儿童成熟B细胞淋巴瘤中应用的效果.方法 回顾性研究,采用历史对照设计.研究对象为北京儿童医院儿童肿瘤中心肿瘤内科初诊并完成治疗的127例成熟B细胞淋巴瘤患儿,分为2组,2020年7月-2021年7月治疗的63例为对照组,给予常规护理模式;2021年8月-2022年8月治疗的64例为管理组.收集两组患儿住院期间的基本临床资料、主要并发症及体重波动、血红蛋白、白蛋白、淋巴细胞绝对值等营养相关指标,并给予管理组全程营养管理.结果 化疗结束后管理组和对照组BMI[(17.1±2.8)kg/m2比(16.0±2.8)kg/m2]、营养不良评分[(0.2±1.1)比(-0.3±1.4)]、白蛋白[(43.7±3.5)g/L比(40.9±3.9)g/L]、前白蛋白[(208.9±59.8)mg/L比(188.9±43.5)mg/L]及淋巴细胞绝对值[(1.1±0.6)×109/L比(0.9±0.4)× 109/L]均优于对照组,差异有统计学意义(P＜0.05);肺炎(23.4％比39.7％)、败血症(14.1％比31.7％)、其它感染(15.6％比33.3％)发生率均低于对照组,差异有统计学意义(P＜0.05),其它并发症发生率均无统计学意义(P＞0.05);转入ICU(4.7％比15.9％)、非化疗入院(32.8％比50.8％)和营养不良(11.1％比25.0％)比例均低于对照组,差异有统计学意义(P＜0.05).结论 优化营养管理,可改善患儿营养状况和预后,避免营养相关不良事件发生.

1 病例资料 男,9 岁 11 月,因"腹痛、间断血尿 2 周余"于2020年2月入首都医科大学附属北京儿童医院. 患儿自起病以来无发热,体重减轻3 kg. 既往史、个人史和家族史无特殊.

Background Chimeric antigen receptor (CAR)-T cell therapy has been used to treat pediatric refractory or relapsed mature B-cell non-Hodgkin lymphoma (r/r MB-NHL) with significantly improved outcomes, but a proportion of patients display no response or experience relapse after treatment. To investigate whether tumor-intrinsic somatic genetic alterations have an impact on CAR-T cell treatment, the genetic features and treatment outcomes of 89 children with MB-NHL were analyzed. Methods 89 pediatric patients treated at multiple clinical centers of the China Net Childhood Lymphoma (CNCL) were included in this study. Targeted next-generation sequencing for a panel of lymphoma-related genes was performed on tumor samples. Survival rates and relapse by genetic features and clinical factors were analyzed. Survival curves were calculated using a log-rank (Mantel-Cox) test. The Wilcox sum-rank test and Fisher’s exact test were applied to test for group differences. Results A total of 89 driver genes with somatic mutations were identified. The most frequently mutated genes were TP53 (66%), ID3 (55%), and ARID1A (31%). The incidence of ARID1A mutation and co-mutation of TP53 and ARID1A was high in patients with r/r MB-NHL ( P = 0.006; P = 0.018, respectively). CAR-T cell treatment significantly improved survival in r/r MB-NHL patients ( P = 0.00081), but patients with ARID1A or ARID1A and TP53 co-mutation had poor survival compared to those without such mutations. Conclusion These results indicate that children with MB-NHL harboring ARID1A or TP53 and ARID1A co-mutation are insensitive to initial conventional chemotherapy and subsequent CAR-T cell treatment. Examination of ARID1A and TP53 mutation status at baseline might have prognostic value, and risk-adapted or more effective therapies should be considered for patients with these high-risk genetic alterations.

Introduction Classical Hodgkin lymphoma (cHL) accounts for about 4.8% of childhood malignant neoplasm, and the incidence of cHL in Chinese children and adolescents (0-19 years old) is about 1.78/million, which is a group of relatively low malignancy and curable tumor. With the prolonged survival of children and adolescents with cHL, the incidence of muscle and skeletal malformations, lung and cardiovascular diseases, infertility and secondary tumors increased significantly during long-term follow-up. Therefore, the goal of childhood cHL treatment is to achieve and maintain the high efficacy while reduce the treatment-related complications. Brentuximab vedotin (BV), an antibody-drug conjugates (ADC) targeting CD30, has been evaluated well in American children and some regions, but no clinical studies to explore the efficacy and safety of BV in Chinese children with cHL. Therefore, the objective of our study is to evaluate the efficacy (objective response rate, including CR and PR) and safety (short - and long-term safety) of modified BV-AVD-R regimen (Brentuximab vedotin + Rituximab + Doxorubicin + Vinblastine + Dacarbazine) in Chinese children with previously untreated intermediate- and high-risk classical HL. Methods This study is a prospective study with period from October 2022 to December 2024, and planned to enroll 44 children with newly diagnosed intermediate- and high-risk classical HL. All patients will undergo PET/CT at the time of initial diagnosis and after 2 cycles of modified BV+R+AVD regimen to determine early response. Rapid early responders (RER) defined as CR after 2 cycles of therapy. Slow early responders (SER) defined as no CR (partial response (PR) or stable disease) after 2 cycles of therapy. Intermediate-risk patients were stage IA bulk/E, IB, IIA bulk/E, IIB, and IIIA. High-risk patients were stage IIB bulk/E, IIIA bulk/E, IIIB, and IVA/B(Figure 1). The primary endpoints include ORR (CR+PR) and adverse events. The secondary endpoints include progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) at 6 months and 1 year. Results From October 2022 to July 2023, a total of 14 children with newly diagnosed classical HL were enrolled, and 12 patients who had completed at least 2 cycles treatment were eligible for evaluation. 9 boys and 3 girls were enrolled, with median age of 10 years (range 7-15 years). Risk group: 9 patients in high-risk group, 3 patients in intermediate-risk group; Clinical stage: 5 patients in stage IIIA, 2 patients in stage IIIB, 4 patients in stage IVA, and 1 patient in stage IVB. Pathologic subtype: 7 patients of nodular sclerosis type and 5 patients of mixed cell type. Treatment: A total of 33 cycles of modified BV+R+AVD regimen were completed, with 66 doses of BV. The median number of treatment cycles was 3 cycles (range 2-6). 11 patients achieved CR and 1 patient achieved PR after 2 cycles, and the ORR was 100% (12/12). As of July 28, 2023, 4 children had stopped follow-up and achieved CR without sequential radiotherapy. The median follow-up was 6 months (range 2-10). 12 patients successfully received and completed BV infusions, mild nausea and vomiting (10/12), alopecia (9/12) and sensory abnormalities (3/12) were observed. Serious adverse events were mainly grade ≥3 blood cell abnormalities (10/12), none of which had an impact on the treatment flow. No patient withdrew from the study, indicating good adherence to the regimen. Conclusion The risk-adapted modified BV+R+AVD regimen for newly diagnosed Chinese children and adolescents with classical HL showed favorable treatment outcomes with good early response rate and sustained response rate. The regimen could also reduce sequential radiotherapy and demonstrated well safety and tolerability. The study is still ongoing.

INTRODUCTION: Hodgkin Lymphoma (HL) is a familiar malignant lymphoma of the lymphatic system that accounts for 10% of all lymphoma diagnoses and 5% of lymphoma-related deaths. According to statistics, the incidence of HL in children and adolescents (0-19 years old) in China is about 1.78/million, and an average of 569 new cases are estimated annually from 2019 to 2021 . Brentuximab vedotin (BV) is an antibody-drug conjugates (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. Most of the data on the efficacy and safety of BV came from prospective and retrospective studies in adults or foreign children, and there are insufficient data in Chinese children. The purpose of this study is to explore the efficacy and safety of BV Combined with chemotherapy in Chinese pediatric patients with refractory and/or relapsed Hodgkin's lymphoma. METHODS: Retrospective analysis of clinical data of 9 children with refractory and/or relapsed Hodgkin's lymphoma from October 2021 to May 2023 at Beijing Children's Hospital, Capital Medical University. Patients were classified according to: clinical stage(Ann Arbor stage), huge tumor, huge tumor in the mediastinum, symptoms of B, and whether multiple lymph nodes were involved. Among them, the low-risk group was IA, ⅡA without giant tumor. The middle risk group was IB and ⅢA without huge tumor. High-risk groups were patients with stage ⅡB, ⅢB, Ⅳ or (each stage) with large tumors, or children with > 4 lymph node regions. All patients received BV in combination with chemotherapy for at least 2 cycles, and patients were assessed for remission response according to the Revised Response Criteria for Malignant Lymphoma at the end of every 2 cycles and followed up until July 20, 2023. RESULTS: Totally 32 cycles of chemotherapy were recorded, including 36 doses of BV administration(Table 1). The overall response rate of the children after 2 cycles of treatment was 100%, and the complete response rate was 88.89%. After remission, 2 cases (P1, P2) were treated with BV single drug 1.8mg/kg, Q3W for 6 months, and 3 cases (P3, P4, P7) were treated with radiotherapy. Two patients (P5, P6) received sequential chemotherapy, and two patients (P8, P9) were followed by programmed cell death 1(PD-1) antibody maintenance treatment for 6 months. After receiving PD-1 antibody for 6 months, 1 patient (P9) was transferred to BV monotherapy for maintenance, with 18 times planned. 2 cases (P1, P2) were then treated with autologous stem cell transplantation. None of the children developed disease progression during treatment. All patients successfully completed all planned dosage of BV, and serious adverse events were dominated by grade 3 or higher hematocrit, none of which interfered with normal treatment. Interpretation. BV had demonstrated the better efficacy and tolerable safety profile in the treatment of refractory and/or relapsed Hodgkin's lymphoma in children. CONCLUSIONS: BV has been approved by National Medical Products Administration in China since 2020, the clinical cases are mostly from adult lymphoma patients, and children data of in China is rare. In this study, we retrospectively reviewed and analyzed the data of BV combined chemotherapy in the treatment of refractory and relapsed Hodgkin lymphoma from single center, and found that the treatment response was rapid, continuousand safe. However, this study is a single-center retrospective study with a small sample size So We are conducting a prospective study of BV in first-line Hodgkin lymphoma children patients in China and aiming to generate more data for this specific population.