Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.
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 summarize the long-term efficacy of Beijing Children's Hospital-2009-lymphoblastic lymphoma (BCH-2009-LBL) in the treatment of T-lymphoblastic lymphoma (T-LBL) in children and adolescents and to explore the prognostic factors. Methods: T-LBL children admitted to Beijing Children's Hospital Affiliated to Capital Medical University from January 2009 to April 2017 were retrospectively included. 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 the BCH-2009-LBL protocol, with follow-up until December 31, 2023. The clinical characteristics and therapeutic effect of each group were compared. Survival curve was drawn by Kaplan-Meier method, and the difference in survival rate between groups was compared by log-rank test. Multivariate Cox regression model was used to analyze the prognostic factors. Results: A total of 146 patients were included, the age of disease onset [M(Q1, Q3)] was 8.0 (1.5, 14.0) years old. There were 107 (73.3%) males and 39 (26.7%) females. Clinical staging: 1 case in stage Ⅰ and 1 case in stage Ⅱ (0.7% each), 41 cases (28.1%) cases in stage Ⅲ and 103 cases(70.5%) in stage Ⅳ. There were 1 case (0.7%), 93 cases (63.7%), and 52 cases (35.6%) in the low, intermediate, and high-risk groups, respectively. The follow-up time was 121 (80, 180) months, and the 5-year and 10-year event-free survival (EFS) rates were 76.4% and 75.0%, respectively. The 5-year EFS rates of low, intermediate and high risk groups were 100.0%, 81.3% and 67.3%, respectively. There was significant difference in remission between the middle-risk group and the high-risk group on the 8th day of hormone pretreatment and at the end of induction (both P<0.05). Recurrence/progression occurred in 29 cases (recurrence rate 19.9%), and the recurrence time was 15 (3, 74) months, in which 26 cases died and only 3 cases survived. Infection-related death occurred in 6 cases (4.1%). The failure or progression of hormone pretreatment at d8 (HR=10.089, 95%CI: 1.266-80.387, P=0.029) and the failure to achieve complete remission at the end of induction (mid-term evaluation) (HR=7.638, 95%CI: 2.411-24.199, P=0.001) were the risk factors for EFS rate of intermediate risk group. The above indexes had no statistical significance on EFS rate in high-risk groups (all P>0.05). Conclusions: BCH-2009-LBL regimen shows good efficacy in the treatment of pediatric T-LBL. The failure or progression of hormone pretreatment at d8 and the failure to achieve complete remission at the end of induction (mid-term evaluation) were the risk factors for EFS rate.
Objective: To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin's lymphoma (R/R cHL). Methods: Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment. Conclusion: Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin's lymphoma in children.
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.
A male child, aged 5 years and 3 months, was admitted to the Oncology Department with a history of pain in both hip joints, headache, and diplopia lasting for 40 days. Physical examination did not reveal definitive signs or obvious abnormalities in the nervous system. Imaging studies showed only abnormalities in the craniocerebrum and spinal cord. Routine cerebrospinal fluid (CSF) analysis revealed elevation in the total number of white blood cells, mainly mononuclear cells. Biochemical analysis of CSF showed normal glucose and chloride levels, and increased protein concentrations. The possibility of central nervous system (CNS) infection was initially considered. Subsequently, antibacterial and antiviral therapy was administered; however, this treatment was ineffective. Further examination of CSF through immunophenotyping revealed mature B-cell lymphoma with CNS involvement; there were no neoplastic lesions detected elsewhere in the body. Thus, the patient was diagnosed with primary central nervous system lymphoma (PCNSL). Complete remission was achieved after chemotherapy with the CNCL-2017-mature B-cell lymphoma regimen. Thus far, all chemotherapy cycles have been completed, the patient remains in complete remission, and the follow-up is ongoing. Clinicians should pay close attention to PCNSL in children.
医源性免疫缺陷相关淋巴增殖性疾病指的是异基因造血干细胞移植或器官移植后发生的淋巴增殖性疾病,通常与EBV相关.而其他医源性免疫缺陷相关淋巴增殖性疾病(Other iatrogenic immunodeficiency associated lympholifera-tive disorders,OIIA-LPDs)则是在原发病接受免疫抑制药物治疗或其他非移植治疗后的患者中发生的继发的淋巴增殖性疾病[1].本文报道1例儿童T淋巴母细胞淋巴瘤(T-lymphoblastic lymphoma,T-LBL)在维持化疗期间发生的Epstein-Barr 病毒(Epstein Barr virus,EBV)相关 OIIA-LPDs的临床特征、治疗过程及预后,指出其管理策略与原发淋巴瘤不同,旨在提高对这一疾病的认识.
Introduction: Aim to find the efficacy treatment strategy for refractory/relapsed(r/r) patients with pediatric mature B-cell lymphoma (MBL) by summarizing the treatment outcome of 46 patients from Chinese Children's Lymphoma Multi-center Cooperation Group (CNCL). Methods: The MBL children treated from 1 May 2017 to 31 December 2022 were enrolled. The modified LMB89/96 protocol was adopted for the initial treatment. Clinical characteristics and risk factors were analyzed with r/r patients. Two treatment groups after r/r: salvage chemotherapy (ICE protocol), chimeric antigen receptor T-cell (CAR-T) group. OS and EFS were both analyzed. Results: Total of 861 newly diagnosed children with MBL ≤ 18 years old were enrolled in this study, of which 46(5.3%) cases were relapsed or refractory(R/R). Baseline characteristics of 46 patients: the median age was9 (1∼16) years old, 38/46 males, 8/46 females. Stage I-II was 0/46, Stage III–IV was 19/46 and 27/46 according to St. Jude's stage, of which 11/46 (23%) had a leukemia stage, and 14 (30.4%) had CNS invasion. Risk grouping: group B: 3 cases (%), group C1: 28/46 cases group C2: 14/46 cases. Pathological types: 34/46 cases of Burkitt's lymphoma, 5/46 cases of diffuse large B-cell lymphoma, 5/46 cases of high grade B-cell lymphoma, and 2/46 cases of other types. There were 17/46 with bulky disease, 26/46 cases with LDH > 1000 U/L. Univariate analysis showed that LDH > 1000, Bulky disease, leukemia stage and CNS invasion before initial chemotherapy was significantly related to poor survival. Treatment result: the median follow-up time was 12.49 months (95% CI: 12.86, 23.99), (0.3∼59.6) months, 46 patients with r/r. Salvage treatment: 24 patients received second-line chemotherapy: 6 patients got a CR2, 6 patients quit to treatment due to SD/PD, 4 patients got a treatment related death, 8 patients died of PD/SD. The median survival time was 4.3 months (0.3∼45.9), 2-year OS was 33.33 ± 15.90%. Discussion and conclusion: The outcomes with r/r patients treated with salvage chemotherapy is poor, CART therapy can significantly improve the outcomes of r/r patients, and is expected to be an effective treatment strategy for children with r/r MBL. Keywords: chemotherapy, immunotherapy, non-Hodgkin (pediatric, adolescent, and young adult) No conflicts of interests pertinent to the abstract.
Introduction: Mature B-cell non-Hodgkin's lymphoma (MB-NHL) and T-cell lymphoblastic lymphoma (T-LBL) account for ∼50% and ∼20%, respectively, among the different pediatric NHL entities. Our understanding of the genetic lesions and profiling of these patients may help to improve the clinical management of patients with these lymphomas. The aim of this study is to analyze the mutational status and the associations between genetic features and treatment outcomes in the Chinese pediatric lymphoma cohort. Methods: A total of 207 patients treated at multiple clinical centers of the Chinese Children's Lymphoma Collaborative Group (CNCL) from 2017 to 2023 were included in this retrospective study. Targeted next-generation sequencing (t-NGS) with a panel of lymphoma-related genes was performed on tumor samples collected at the time of initial diagnosis and at tumor of refractory or relapse (r/r), and the correlations of somatic mutations with survival rates as well as with relapse and other clinical factors were analyzed. Results: A total of 136 driver genes with somatic mutations were detected in the entire cohort. In 133 pediatric MB-NHL patients, the most frequently mutated genes from 77 initially diagnostic samples were ID3 (52%), TP53 (47%), CCND3 (30%), ARID1A (29%), and DDX3X (27%) (Figure 1a). In 56 r/r samples, the most commonly mutated genes were TP53 (84%), followed by ID3 (59%), ARID1A (41%), CCND3 (32%), and DDX3X (25%) (Figure 1b). TP53 mutation was significantly more frequent in r/r samples than that in initially diagnostic samples (p < 0.001) and patients with TP53 mutations had poor survival (log-rank p = 0.0013, Figure 1c). Among patients treated with chimeric antigen receptor T-cell (CAR-T) therapy, those with ARID1A mutations exhibited poorer response to CAR-T treatment and shorter overall survival compared with the patients without such mutations (mOS = 180 days, log-rank p = 0.00081, Figure 1d). In 74 pediatric T-LBL patients,the most commonly mutated genes were NOTCH1 (50%), followed by FBXW7 (26%), JAK1 (16%), NRAS (16%), and JAK3 (11%) (Figure 1e). Genes in the JAK signaling pathway were more frequently mutated in Chinese patients than the corresponding western patients, such as JAK1 (16% vs. 2%) and JAK3 (11% vs. 5%). Further analysis showed that the incidence of NOTCH1 (68% vs. 27%) and FBXW7 (37% vs. 12%) mutations in patient group with initial remission (n = 41) was significantly higher than that in patient group with r/r T-LBL (n = 33) (p = 0.005, p = 0.036, respectively, Figure 1f), indicating that NOTCH1 and FBXW7mutations were associated with good prognosis. Keywords: diagnostic and prognostic biomarkers, immunotherapy, non-Hodgkin (pediatric, adolescent, and young adult) No conflicts of interests pertinent to the abstract.
Introduction: To investigate the prognostic factors of childhood mature B-cell lymphoma (MBL), especially the significance of somatic mutations in the clinical features and prognosis, by analyzing the clinical chartacteristics, genetic mutation results and prognosis of 133 children with MBL. Methods: Children and adolescents (≤18 years old) with MBL who were admitted from November 2017 to February 2023 were enrolled, and patients with somatic mutations were detected using next-generation sequencing (NGS). The diagnosis includes the completion of pathological examination and center consultation, and the staging is based on the international children's St. Jude staging system, primary patients were treated with the modified LMB89/96 protocol. Refractory or recurrent (r/r) patients were treated with second-line chemotherapy based on ICE and/or CAR-T-cell sequential therapy with different B-cell targets. The factors related to curative effect and prognosis, especially the correlation between the gene mutation spectrum and prognosis, were analyzed. Results: The mutant gene spectrum of 133 patients is shown in Fig.a. According to the time of specimen collection, there were 77 cases of initial diagnosis (initial treatment group) and 56 cases of r/r patients (r/r group). The clinical feature and survival of the 133 patients are summarized in Figure b, c, d, e (P < 0.001) and g. The results showed that patients with a large tumor focus, serous cavity effusion and delayed chemotherapy during treatment had significant difference in prognosis and significantly shortened survival. The top three genes in the initial treatment group were ID3 (53%), TP53 (47%), and CCND3 (30%) (Figure h). The top three genes in the r/r group were TP53 (82%), ID3 (58%), and ARID1A (40%) (Figure j). TP53 was significantly different between the initial treatment group and r/r patients (P < 0.001). Of the 133 patients grouped by efficacy, 70 progressed/relapsed, and 59/70 received CAR T therapy, with an overall response rate (ORR) of 83%. Survival analysis is shown in the figure f. A total of 11/70 patients received second-line chemotherapy, and only 1 patient survived to receive treatment. Compared with second-line chemotherapy, CAR T-cell treatment significantly improved the survival rate (P = 0.008). ARID1Awas significant in patients with poor prognosis after CAR T therapy (P = 0.00081) (Figure k). Keywords: Chemotherapy, Diagnostic and Prognostic Biomarkers, Non-Hodgkin (Pediatric, Adolescent, and Young Adult) No conflicts of interests pertinent to the abstract.
Objective: To summarize changes of serum immunoglobulin levels before and after chemotherapy in children with Burkitt lymphoma (BL), so as to investigate the effects of chemotherapy and rituximab on serum immunoglobulin levels in children with BL. Methods: Clinical data of 223 children with newly diagnosed Burkitt lymphoma at Beijing Children's Hospital from January 2009 to April 2017 were analyzed retrospectively. They were treated according to the modified LMB 89 regimen and some of them received combined rituximab therapy during the chemotherapy. The serum immunoglobulin (IgA, IgM, IgG) before chemotherapy, at the time of discontinuing chemotherapy, as well as 6, 12, 24, 36 months after chemotherapy were collected. Changes of serum IgA, IgM and IgG with time among different treatment groups were compared using repeated measures ANOVA. Results: According to risk group, 223 children were devided into group B(n=53)and group C(n=170). Before chemotherapy, 109 cases (48.9%) were combined with hypogammaglobulinemia. The serum IgA, IgM, and IgG levels of all the patients were (0.9±0.7), 1.2 (0.5, 1.3) and (7.2±2.9) g/L before chemotherapy, (0.5±0.4), 0.2 (0.1, 0.3) and (6.3±2.3) g/L at the time of discontinuing chemotherapy (t=13.63, Z=-11.99, t=4.57, all P<0.05). There were statistical difference in IgA, IgM levels of group B and IgA, IgM, IgG levels of group C before chemotherapy and at the time of discontinuing chemotherapy (t=8.86, Z=-6.28, t=11.19, Z=-10.15, t=4.50, all P<0.05). The differences of serum IgA and IgG levels at the time after chemotherapy among patients treated with chemotherapy alone and those treated with chemotherapy combined rituximab in group B and C were significant (F=5.38, P=0.002 and F=4.22, P=0.007). Conclusions: Approximately half of children with BL have already existed hypogammaglobulinemia at initial diagnosis prior to the start of treatment. The modified LMB 89 regimen have significant effect on humoral immunity of children with BL. In the process of immune reconstruction after chemotherapy, rituximab has more significant effect on serum IgA and IgG levels in BL patients.
Background: Refractory and relapsed (r/r) anaplastic lymphoma kinase (ALK)-positive anaplastic large cell Lymphoma(ALK+ALCL) have a poor prognosis. Studies had confirmed vinblastine (VBL) may be an effective treatment for relapsed ALCL and ALK inhibitors may have high efficacy and tolerability in patients carrying ALK fusions. Therefore, we put forward a hypothesis that for those r/r ALK+ALCL patients with poor chemotherapy tolerance and effect, combining ALK inhibitors with vinblastine may have a sustained anti-tumor effect and good tolerance. Aims: To assess the efficacy and safety of ALK inhibitors combined with VBL in pediatric relapsed/refractory (r/r) ALK+ ALCL. Methods: Patients aged between 0 and 18 years with r/r ALK+ ALCL were included in this trial. ALK inhibitors are given orally with a converted dosage according to body surface area and VBL was given with injection once a week at 4-6 mg/(m2.week). And no intensive chemotherapy and hematopoietic stem cell transplantation will be in our study.We may decrease the dosage of VBL or delete VBL if patients suffer severe bone marrow suppression, repeated infections, and peripheral neuritis and other VBL-related toxicities. Available ALK inhibitors included crizotinib(CZ), alectinib(AL) and ceritinib(CER). Patients without CNS involvement took CZ, and patients with CNS involvement took AL or CER. A cycle of therapy is 28 days. Evaluation for responses toxicities were monitored and recorded. Results:27 patients were enrolled in this trial between April 2018 and April 2021. The median age was 8.3 years old(ranging from 0.75 to 16), male/female ratio is19:8. By St.jude's staging, 20 cases were in stage III (74.1%), 7 cases in stage IV (25.9%) including 3 cases (11.1%) with CNS involvement at initial diagnosis. Before being enrolled in our study, 6 patient (22.2%) failed to achieve CR with prior 4-10 chemotherapy regimens, 21 patients (77.8%) relapsed after an average of 5-16 courses of standard pulse chemotherapy regimens. After 1st cycle of treatments, 62.9%(17/26) achieved comlpele remission(CR) without measurable tumors and ALK gene transcription, no progressed cases. Additional 6 case got CR after 2-10 month(23.1%). In general, 7 patients withdraw due to death, progress, ineffectiveness, economics, adverse reactions. The treatment retention rate was ,7.1%(20/7),objective response rate (ORR) was 85.2%(23/27), best complete remission rate(CRR) was 85.2%(23/27), disease control rate(DCR) was 92.5%(25/27), average duration of CR was 14.85 months(0-36months). Toxicities included nausea and vomiting, stomachache, diarrhea(81.5%,22/27, one or more above toxicities), neutropenia (27/27), pneumonia(7.4%, 2/27), sepsis(7.4%, 2/27), creatine kinase-MB elevation (81.5%,22/27,all are in crizotinib group including 2 abnormal ECG cases), liver enzyme elevation (63.%,17//27), intestinal obstruction(7.4%, 2/26). 2 cases relapsed because of the treatment discontinuation due to severe elevated liver enzymes. Summary/Conclusion: ALK inhibitors combined with VBL may rapidly induce the tumor remission of r/r ALK+ALCL and the tolerance is good. Combination therapy may induce a more lasting remission in for patients without BM involvement. Patients with BM involvement are more likely to fail treatment. Sequential use of ALK kinase inhibitors may be an efficient strategy to counter drug resistance.More data and longer follow-up time are needed to support our study. Figure 1 Figure 1. No relevant conflicts of interest to declare.
In this study the photocatalytic behavior of as-anodized and heat treated surfaces of Ti6Al4V was investigated electrochemically in methylethionium chloride solution in dark and under illumination at 60 W and 100 W. X-ray diffraction pattern of as-anodized surface revealed oxygen deficient Ti6O phase, which was converted to rutile/anatase phases by heat treatment in air. Potentiodynamic scans showed variation in current density during anodic polarization due to the electronic traps within sub-band energy states by the amorphous nature of as formed structure hence lower catalytic activity than heat-treated specimen. Impedance spectroscopy of heat-treated surface in dye solution under dark and light depicted lower charge transfer resistance, recombination admittance and higher charge transfer coefficient than as-anodized. The UV–vis spectroscopy of heat treated TiO2 nanotubular structure represented 45.05% photocatalytic efficiency.
The performances of p–i–n amorphous silicon germanium (a-SiGe:H) solar cell modules were investigated post annealing at different temperatures. When the annealing temperature is 190 °C, the best performance of solar cell modules is obtained. The efficiency of solar cell modules is improved from 5.11% to 7.91%. The enhancement in quantum efficiency spectra at long wavelength post annealing may be attributable to there being significantly less absorption in intrinsic layer. The microstructural properties of the a-SiGe:H thin films are investigated post annealing at different temperatures. The results show that the low temperature annealing process leads to the improvement in the film microstructure.
Purpose The purpose of this study is to survey the prevalence and morphology of the maxillary sinus septum, which might increase the rate of maxillary sinus membrane perforation during maxillary sinus floor elevation surgery, among northern Chinese, and to further analyze the relationship between gender, age, edentulous type, and prevalence of maxillary sinus septa. Methods The cross-sectional retrospective study was based on an analysis of Cone Beam Computed Tomography (CBCT) images of maxillary sinus which had been obtained from patients who visited radiology department of Beijing Stomatology Hospital of Capital Medical University (Beijing, China) during the period from January 2019 to December 2019. The data of demographic characteristic, prevalence, position, direction, and morphology of maxillary sinus septum were collected and further analyzed by SPSS version 25.0.1 and R version 3.5.1 software program. Results 595 patients were included in this study, and 1190 maxillary sinuses were analyzed and the incidence rate of the sinus septum was 46.9%. 399 (33.5%) sinuses had one or more septa in 279 (46.9%) patients. In addition, maxillary sinus septa incidence showed no significant differences among gender, age, and edentulous type. The segment second molar had the highest incidence rate of septa. Conclusion In this study, a higher incidence of the maxillary sinus septum was found in the northern Chinese, and its distribution varied with its position, morphology, and direction.
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 (χ 2=4.16, P=0.041) and group C2 (χ 2=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)% (χ 2=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.
BACKGROUND/AIMS Under-estimating the damage caused by trauma to the dental structures may delay treatment. Timely and accurate diagnosis remains challenging in clinical practice. Radiography is an important modality for the diagnosis of traumatic injuries. The aim of this study was to compare the efficacy of periapical radiography and cone beam computed tomography for the diagnosis of trauma to the anterior maxillary dentoalveolar region in children and adolescents. MATERIAL AND METHODS Images of patients who underwent both periapical radiography and cone beam computed tomography simultaneously because of trauma to the anterior maxillary region between January 2016 and January 2020 were analyzed retrospectively. Pairwise comparison between the receiver operating characteristic curves was performed to statistically compare the two methods for the diagnosis of crown fractures, root fractures, alveolar bone fractures and luxations, tooth resorption, and periapical radiolucencies. RESULTS A total of 190 patients met the inclusion criteria. There were 120 (63.2%) males and 70 (36.8%) females, with a mean age of 11.1 years (range: 6-17 years). A crown fracture was observed in 144 teeth, while a root fracture was observed in 71 teeth. Alveolar fracture and luxation were observed in 44 incisors. During follow-up, tooth resorption and periapical radiolucencies were observed in 25 and 33 teeth, respectively. Pairwise receiver operating characteristic curve analysis revealed that cone beam computed tomography was significantly superior to periapical radiography for the diagnosis of root fractures, alveolar fractures and luxations, and tooth resorption (p < .05). However, no significant differences were found for the diagnosis of crown fractures and periapical radiolucencies (p > .05). CONCLUSIONS Cone beam computed tomography in the low-dose mode was better for diagnosing root and bone fractures and resorption, but no different to periapical radiographs for crown fractures and periapical radiolucencies in pediatric patients.
1例9岁男童以面色苍白、脐周疼痛起病,辅助检查提示贫血,13C呼气试验阳性,胃镜可见炎症、溃疡,结合病理形态、免疫组织化学、PCR检测诊断儿童胃黏膜相关淋巴组织淋巴瘤;予抗幽门螺杆菌治疗仍有肿瘤病灶存在,予以化疗,预后良好。该病儿童少见,抗幽门螺杆菌治疗后无好转时需考虑此病,病理、免疫组织化学及PCR检查可明确诊断,低剂量化疗预后好。.
BACKGROUND AND PURPOSE: Flow diverter?induced hemodynamic change plays an important role in the mechanism of intracranial aneurysm occlusion. Our aim was to explore the relationship between aneurysm features and flow-diverter treatment of unruptured sidewall intracranial aneurysms. MATERIALS AND METHODS: MR imaging, 4D phase-contrast, was prospectively performed before flow diverter implantation in each patient with unruptured intracranial aneurysm. Two postprocedure follow-ups were scheduled at 6 and 12?months. Responses were grouped according to whether the aneurysms were occluded or remnant. Preprocedural aneurysm geometries and ostium hemodynamics in 38 patients were compared between the 2 groups at 6 and 12?months. Receiver operating characteristic curve analyses were performed for significant geometric and hemodynamic continuous parameters. RESULTS: After the 6-month assessment, 21 of 41 intracranial aneurysms were occluded, and 9 additional aneurysms were occluded at 12?months. Geometrically, the ostium maximum diameter was significantly larger in the remnant group at 6 and 12?months (both P <?.001). Hemodynamically, the proximal inflow zone was more frequently observed in the remnant group at 6?months. Several preprocedural ostium hemodynamic parameters were significantly higher in the remnant group. As a prediction for occlusion, the areas under the curve of the ostium maximum diameter (for 6 and 12 months), systolic inflow rate ratio (for 6?months), and systolic inflow area (for 12 months) reached 0.843, 0.883, 0.855, and 0.860, respectively. CONCLUSIONS: Intracranial aneurysms with a large ostium and strong ostium inflow may need a longer time for occlusion. Preprocedural 4D flow MR imaging can well illustrate ostium hemodynamics and characterize aneurysm treatment responses.
Introduction: Pediatric patients with relapsed or refractory Burkitt's lymphoma (BL) present as a major challenge due to their poor outcomes despite use of high-intensity chemotherapy and anti-CD20 monoclonal antibody (mAb). CAR-T has shown efficacy in treating refractory or relapsed leukemia and Non-Hodgkin Lymphoma in adult patients. The aim of our study is to assess the safety and efficacy of CAR-T in the treatment of refractory or relapsed BL in pediatric patients. Methods: Patients with refractory/relapsed BL were enrolled to clinical trial (ChiCTR18000144) during January 2018-January 2019. The inclusion criteria were: 1) No complete remission (CR) after at least 5 courses of standard chemotherapy plus anti-CD20 mAb; or 2) No partial remission (PR) or showing progression after 2 courses of second-line chemotherapy; and 3) High expression of at least one B cells markers (CD19/CD20/CD22) examined by immunohistochemistry. The highest expressed marker was chosen for the first round CAR-T target. The therapeutic doses of CAR-T range from 1x10^6 to 3x10^6 per kilogram of body weight each course. The CAR-T cell numbers and cytokines were measured weekly. Tumor responses were evaluated at day 30 and day 60 post infusion and every two months thereafter. Results: Five refractory or relapsed BL patients, aged 6 to 10 years with a median age of 8 years, were enrolled, 4 males (80%) and 1 female (20%) according to St Jude's staging at the initial diagnosis: 3 cases (60%) in stage III, 2 cases (40%) in stage IV, 1 case of CNS invasion (20%), 1 case of bone marrow invasion (20%). They all failed initial intense chemotherapy and anti-CD20 mAb treatment (Table 1). They were then treated with 1 to 3 rounds of CAR-T (Table 2). Patients were monitored for CAR-T side effects: fever, gastro-intestine discomfort, rash, capillary leak syndrome, Immuno-pneumonia, tremor, hypotension, immunocytopenia, abnormal coagulation, liver dysfunction. One patient (20%) was diagnosed of cytokine-release syndrome (CRS) grading I and the other four grading III(80%). All subjects recovered fully after active symptomatic and supportive treatment including application of glucocorticoids in CRS grading III, but no patient required Tombuzumab. There were no death events (Table 2). Three subjects (60%) achieved CR by one round of CD19 CAR-T cell therapy, while two subjects (40%) achieved PR with first round of CD19 CAR-T treatment and achieved CR with subsequent CD22 or CD22 and CD20 CAR-T. The overall response rate (OR) was 100% with a median follow up 249 days, range 62-382 days, last follow up date January 30, 2019. (Table 3). Currently, all patients were in event-free survival. Conclusion: CD19/CD20/CD22-CAR-T therapy showed a robust efficacy in pediatric patients with refractory and relapsed BL and the toxicity profiles were moderate and could be well controlled. Keywords: Burkitt lymphoma (BL); CD19; CD22.