Notch 1 and NF-κB Expression and Clinical Correlation in Chinese Patients with Lymphoblastic Lymphoma

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/T-LBL) is commonly associated with Notch 1 mutations. There is limited data on the relationship between Notch l and NF-κB expression and clinical features in LBL. We evaluated the expression of Notch l and NF-κB in LBL using immunohistochemistry and analyzed their relationship with clinical characteristics, treatment results, and survival. From October 2000 to August 2008, 34 untreated patients with LBL were enrolled in the study. Median age was 11.8 years (range, 1 - 25 years). Twenty-five patients were diagnosed with T-LBL and 9 patients with B-LBL. Most patients received chemotherapy consisting of modified ALL-BFM- 90. Notch l showed high expression in 68% of T-LBL and low expression in 100% of B-LBL (p = 0.015). High expression of Notch l positively correlated with presence of a mediastinal mass but not with 5-year event free survival (EFS) in T-LBL. NF-κB showed high expression in 65% of all patients with LBL, with no difference between T- and B-LBL. NF-κB expression was higher in T-LBL patients with bulky disease and B symptom;it did not correlate with 5-year EFS in T-LBL. Expression of Notch 1 and NF-κB strongly correlated (p = 0.014) in T-LBL. Notch 1 is highly ex- pressed in T-LBL. NF-κB is highly expressed in all patients with LBL with no difference between T-LBL and B-LBL. Notch 1 expression was significantly associated with NF-κB expression in T-LBL. Notch l and NF-κB may play an important role in the development of T-LBL;further investigation is warranted.

Safety and clinical efficacy of sintilimab (anti-PD-1) in pediatric patients with advanced or recurrent malignancies in a phase I study

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.

Outcomes of Burkitt lymphoma with bone marrow involvement or Burkitt leukemia in Chinese children

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.