Clinical characteristics and prognosis of mature B-cell non-Hodgkin lymphoma in children

Abstract

Objective To study clinical features and prognosis of childhood mature B-cell non-Hodgkin lymphoma (B-NHL). Methods Sixty-seven cases of pathologically-confirmed B-NHL from January 2010 to December 2018 in West China Second University Hospital, Sichuan University were enrolled in this retrospective study. According to different pathological types, they were divided into Burkitt lymphoma (BL) group (n=51), diffuse large B-cell lymphoma (DLBCL) group (n=11) and other B-NHL group (n=5, pathological examination results were high proliferative activity B cell lymphoma). The retrospective analysis method was used to collect the clinical data of these subjects, including age, gender, clinical characteristics, laboratory examination results, clinical stages, treatment results and follow-up. Kaplan-Meier method was used to analyze the survival of children with B-NHL in this group, such as 2-year and 5-year overall survival (OS) rate and event-free survival (EFS) rate, and Cox propertional hazards model was used to compare OS and EFS curves among three groups. According to previous research results, combined with clinical experience and single factor analysis results of clinical factors affecting the prognosis of children with B-NHL, multivariate non-conditional logistic analysis was carried out on the influencing factors of prognosis of children with B-NHL. This study was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013. There was no significant difference among 3 groups in the course of the diseases (P>0.05). Results ① The median age of 67 children with B-NHL was 7 years old (1.8-14.6 years old). Among them, 48 cases (71.6%) were boys, and 19 cases (28.4%) were girls, and the ratio of boys to girls was 2.5∶1. There was statistically significant differences in age and gender ratio among three groups (χ2=8.054, 8.677; P=0.018, 0.013). The age and the proportion of boys in DLBCL group were older and higher than those in BL group, respectively, and the differences were statistically significant (Z=2.866, P=0.004; χ2=3.892, P=0.049). ②All of the 67 cases completed imaging examination, bone marrow smear and cerebrospinal fluid examination before chemotherapy. The primary tumor sites in BL group tended to be more common in the abdomen, while peripheral lymph nodes were more commonly involved at disease onset in DLBCL group. In addition, 11 children had bone marrow and CNS involvement (all children in the BL group). ③ Laboratory findings showed that 39 cases (58.2%) had elevated serum LDH levels, with a median serum LDH level of 498 U/L (153-6 640 U/L). The positive expression rate of Bcl-6 (86.4%, 38/44) and the positive rate of C-MYC gene rearrangement (96.3%, 26/27) in BL group were significantly higher than those of 54.5% (6/11) and 0 in DLBCL group, and the differences were statistically significant (χ2=6.960, 26.527; P=0.031, 0.05). The median time to recurrence was 9 months (2-37 months), and the 2-year and 5-year cumulative incidence of relapse (CIR) were 11.3% and 13.9%, respectively. In addition, the 5-year OS rate (71.6%) and 5-year EFS rate (59.7%) in patients with bone marrow/CNS involvement were significantly lower than those of 92.2% and 87.6% in patients without bone marrow/CNS involvement, and the differences were statistically significant (χ2=5.001, 6.319, P=0.025, 0.012). ⑦ The results of univariate analysis for children with recurrence/progression and non-recurrence/progression showed that the proportion of bone marrow/CNS involvement and the incidence rate of tumor lysis syndrome in children with recurrence/progression were 50.0% (4/8) and 25.0% (2/8), respectively, which were significantly higher than those of 11.9% (7/59) and 1.7% (1/59) in children without recurrence/progression, and the differences were statistically significant (χ2=4.946, P=0.026; P=0.036); the CR rate (12.5%, 1/8) within 2 courses in children with recurrence/progression was significantly lower than that of 69.5%(41/59) in children without recurrence/progression, and the difference was also statistically significant (χ2=9.782, P=0.002). ⑧ Combined with the results of existing studies and clinical experience, as well as the results of above univariate analysis, the results of multivariate non-conditional logistic analysis of prognostic factors in children with B-NHL showed that bone marrow/CNS involvement (OR=6.536, 95%CI: 1.085-39.380, P=0.040) and failure to achieve CR within 2 courses of treatment (OR=14.682, 95%CI: 1.582-136.240, P=0.018) were independent risk factors for disease relapse/progression in children with B-NHL. Conclusions BL is the most common type of B-NHL in children, with the ileocecum as the prevalent site of tumor primaries. While DLBCL is the second most common type of B-NHL, which commonly occurs in the peripheral lymph node. Involvements of bone marrow/CNS, and incomplete response within 2 courses of chemotherapy may predict poor prognosis of patients. The clinical outcomes of B-NHL children with stage Ⅳ and relapsed/progressive B-NHL remain to be improved. Key words: Lymphoma, non-Hodgkin; B-lymphocytes; Recurrence; Lost to follow-up; Logistic models; Disease-free survival; Prognosis; Child