Cancer has emerged as the leading cause of mortality worldwide and is driven by numerous intricate factors1.The tropomyosin receptor kinase (TRK) proto-oncogene family consists of the TRKA,TRKB,and TRKC transmembrane ...Cancer has emerged as the leading cause of mortality worldwide and is driven by numerous intricate factors1.The tropomyosin receptor kinase (TRK) proto-oncogene family consists of the TRKA,TRKB,and TRKC transmembrane receptors,which are encoded by the NTRK1,NTRK2,and NTRK3 genes,respectively,and are widely expressed in the nervous system and many non-neuronal tissue types2.TRK signaling plays crucial roles in neuronal development,differentiation,and diverse neuronal functions,such as neuronal survival,synapse formation and plasticity,and axon and dendrite formation,in physiologic processes3.展开更多
Importance Burkitt lymphoma with bone marrow involvement and Burkitt leukemia behave aggressively.Thus far,there are limited data concerning survival and toxicity in Chinese children with Burkitt lymphoma or Burkitt l...Importance Burkitt lymphoma with bone marrow involvement and Burkitt leukemia behave aggressively.Thus far,there are limited data concerning survival and toxicity in Chinese children with Burkitt lymphoma or Burkitt leukemia who have undergone treatment with the non-Hodgkin’s lymphoma Berlin-Frankfurt-Münster-90/95(NHL-BFM-90/95)protocol.Objective To analyze outcomes and toxicity in pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia following treatment with the NHL-BFM-90/95 protocol.Methods Patients aged<18 years with bone marrow involvement/leukemia who were treated with the NHL-BFM-90/95 protocol,with or without rituximab,in Sun Yat-Sen University Cancer Center from April 2004 to December 2018 were included in this retrospective analysis.Results Twenty-five patients were eligible.Burkitt lymphoma with bone marrow involvement and Burkitt leukemia were present in 10 and 15 patients,respectively.Central nervous system infiltration was not observed in any patients.All patients underwent chemotherapy involving NHL-BFM-90/95 protocol.Six courses of treatment were administered to each patient(v-AA-BB-CC-AA-BB-CC).The BFM-90/95 plus rituximab protocol was administered to 13 patients.The median follow-up interval was 31.9 months(range,2.5–158 months).Of the 25 patients,four died:three died of tumor progression and one died of therapy abandonment after relief of tumor lysis syndrome.The estimated 5-year event-free survival and overall survival rates were both 85.8%±5.0%.Interpretation Chinese pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia can achieve optimal treatment outcomes and exhibit good tolerance when using the NHL-BFM-90/95 protocol.展开更多
The aim of this phase I study is to evaluate,for the first time,the safety and efficacy of sintilimab in pediatric patients diagnosed with advanced or recurrent malignancies.During the dose escalation phase,patients r...The aim of this phase I study is to evaluate,for the first time,the safety and efficacy of sintilimab in pediatric patients diagnosed with advanced or recurrent malignancies.During the dose escalation phase,patients received a single intravenous infusion of sintilimab at varying doses of 1,3,and 10 mg/kg.The primary endpoints included the identification of dose-limiting toxicities(DLTs)as well as the evaluation of safety and tolerance.Secondary endpoints focused on assessing objective response rate(ORR),progression-free survival(PFS),and overall survival(OS).A total of 29 patients were enrolled,including 10 individuals diagnosed with Hodgkin lymphoma(HL)and 19 patients with various other tumor categories.Notably,diverse pathological types such as thymoma,choroid plexus carcinoma,and NK/T-cell lymphoma were also included in the study cohort.By the safety data cutoff,most adverse events were grade 1 or 2,with grade 3 or higher treatment-related adverse events(TRAE)occurring in 10%of patients.Among the 27 evaluated subjects,four achieved confirmed complete response(CR)while seven patients exhibited confirmed partial response(PR).Additionally,seven patients maintained disease(SD)during the study period.Notably,sintilimab demonstrated remarkable tolerability without DLTs and exhibited promising anti-tumor effects in pediatric HL.Whole-exome sequencing(WES)was conducted in 15 patients to assess the mutational landscape and copy number variation(CNV)status.The completion of this phase I study establishes the foundation for potential combination regimens involving sintilimab in childhood cancer treatment.The trial is registered on ClinicalTrials.gov with the identifier NCT04400851.展开更多
基金supported by grants from the National Key Research and Development Program of China (Grant No.2022YFC2705005)the National Natural Science Foundation of China (Grant No.82203303)the Basic and Applied Basic Research Foundation of Guangdong Province (Grant No.2021A1515110234)。
文摘Cancer has emerged as the leading cause of mortality worldwide and is driven by numerous intricate factors1.The tropomyosin receptor kinase (TRK) proto-oncogene family consists of the TRKA,TRKB,and TRKC transmembrane receptors,which are encoded by the NTRK1,NTRK2,and NTRK3 genes,respectively,and are widely expressed in the nervous system and many non-neuronal tissue types2.TRK signaling plays crucial roles in neuronal development,differentiation,and diverse neuronal functions,such as neuronal survival,synapse formation and plasticity,and axon and dendrite formation,in physiologic processes3.
基金The authors would like to thank the participants and study staff of Sun Yat-sen Univesity Cancer Center for their contributions to this article.
文摘Importance Burkitt lymphoma with bone marrow involvement and Burkitt leukemia behave aggressively.Thus far,there are limited data concerning survival and toxicity in Chinese children with Burkitt lymphoma or Burkitt leukemia who have undergone treatment with the non-Hodgkin’s lymphoma Berlin-Frankfurt-Münster-90/95(NHL-BFM-90/95)protocol.Objective To analyze outcomes and toxicity in pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia following treatment with the NHL-BFM-90/95 protocol.Methods Patients aged<18 years with bone marrow involvement/leukemia who were treated with the NHL-BFM-90/95 protocol,with or without rituximab,in Sun Yat-Sen University Cancer Center from April 2004 to December 2018 were included in this retrospective analysis.Results Twenty-five patients were eligible.Burkitt lymphoma with bone marrow involvement and Burkitt leukemia were present in 10 and 15 patients,respectively.Central nervous system infiltration was not observed in any patients.All patients underwent chemotherapy involving NHL-BFM-90/95 protocol.Six courses of treatment were administered to each patient(v-AA-BB-CC-AA-BB-CC).The BFM-90/95 plus rituximab protocol was administered to 13 patients.The median follow-up interval was 31.9 months(range,2.5–158 months).Of the 25 patients,four died:three died of tumor progression and one died of therapy abandonment after relief of tumor lysis syndrome.The estimated 5-year event-free survival and overall survival rates were both 85.8%±5.0%.Interpretation Chinese pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia can achieve optimal treatment outcomes and exhibit good tolerance when using the NHL-BFM-90/95 protocol.
基金The National Natural Science Foundation of China(No.82002835)The National Key Research and Development Project(No.2022YFC2705005)Guangzhou Science and Technology project(No.202201011572).
文摘The aim of this phase I study is to evaluate,for the first time,the safety and efficacy of sintilimab in pediatric patients diagnosed with advanced or recurrent malignancies.During the dose escalation phase,patients received a single intravenous infusion of sintilimab at varying doses of 1,3,and 10 mg/kg.The primary endpoints included the identification of dose-limiting toxicities(DLTs)as well as the evaluation of safety and tolerance.Secondary endpoints focused on assessing objective response rate(ORR),progression-free survival(PFS),and overall survival(OS).A total of 29 patients were enrolled,including 10 individuals diagnosed with Hodgkin lymphoma(HL)and 19 patients with various other tumor categories.Notably,diverse pathological types such as thymoma,choroid plexus carcinoma,and NK/T-cell lymphoma were also included in the study cohort.By the safety data cutoff,most adverse events were grade 1 or 2,with grade 3 or higher treatment-related adverse events(TRAE)occurring in 10%of patients.Among the 27 evaluated subjects,four achieved confirmed complete response(CR)while seven patients exhibited confirmed partial response(PR).Additionally,seven patients maintained disease(SD)during the study period.Notably,sintilimab demonstrated remarkable tolerability without DLTs and exhibited promising anti-tumor effects in pediatric HL.Whole-exome sequencing(WES)was conducted in 15 patients to assess the mutational landscape and copy number variation(CNV)status.The completion of this phase I study establishes the foundation for potential combination regimens involving sintilimab in childhood cancer treatment.The trial is registered on ClinicalTrials.gov with the identifier NCT04400851.
