Clinical Characteristics and Treatment Outcomes of Pediatric Patients with Non-Hodgkin Lymphoma in East Asia

Suh, Jin Kyung; Gao, Yijin; Tang, Jingyan; Jou, Shiann-Tarng; Lin, Dong‐Tsamn; Takahashi, Yoshiyuki; Kojima, Seiji; Zhang, Yonghong; Seo, Jong Jin

doi:10.4143/crt.2019.219

Cited by 7 publications

(6 citation statements)

References 23 publications

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“…T-LBL generally presents with a mediastinal mass and advanced-stage disease and may involve the bone marrow and, less often, the CNS at diagnosis ( 4 ). In this study, most of the children were males, consistent with a previous report ( 15 ). Furthermore, Almost all cases were in stage III or IV at the time of initial diagnosis, and there were no stage I cases.…”

Section: Discussionsupporting

confidence: 93%

iTRAQ-Based Proteomic Analysis Reveals Potential Serum Biomarkers for Pediatric Non-Hodgkin’s Lymphoma

Yang

et al. 2022

Front. Oncol.

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Non-Hodgkin’s lymphoma (NHL) is the third most common malignant tumor among children. However, at initial NHL diagnosis, most cases are at an advanced stage because of nonspecific clinical manifestations and currently limited diagnostic methods. This study aimed to screen and verify potential serum biomarkers of pediatric NHL using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis. Serum protein expression profiles from children with B-NHL (n=20) and T-NHL (n=20) and healthy controls (n=20) were detected by utilizing iTRAQ in combination with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC–MS/MS) and analyzed by applying Ingenuity Pathway Analysis (IPA). The candidate biomarkers S100A8 and LRG1 were further validated by using enzyme-linked immunosorbent assays (ELISAs). Receiver operating characteristic (ROC) analysis based on ELISA data was used to evaluate diagnostic efficacy. In total, 534 proteins were identified twice using iTRAQ combined with 2D LC–MS/MS. Further analysis identified 79 and 73 differentially expressed proteins in B-NHL and T-NHL serum, respectively, compared with control serum according to our defined criteria; 34 proteins were overexpressed and 45 proteins underexpressed in B-NHL, whereas 45 proteins were overexpressed and 28 proteins underexpressed in T-NHL (p < 0.05). IPA demonstrated a variety of signaling pathways, including acute phase response signaling and liver X receptor/retinoid X receptor (LXR/RXR) activation, to be strongly associated with pediatric NHL. S100A8 and LRG1 were elevated in NHL patients compared to normal controls according to ELISA (p < 0.05), which was consistent with iTRAQ results. The areas under the ROC curves of S100A8, LRG1, and the combination of S100A8 and LRG1 were 0.873, 0.898 and 0.970, respectively. Our findings indicate that analysis of the serum proteome using iTRAQ combined with 2D LC–MS/MS is a feasible approach for biomarker discovery. Serum S100A8 and LRG1 are promising candidate biomarkers for pediatric NHL, and these differential proteins illustrate a novel pathogenesis and may be clinically helpful for NHL diagnosis in the future.

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Section: Discussionsupporting

confidence: 93%

iTRAQ-Based Proteomic Analysis Reveals Potential Serum Biomarkers for Pediatric Non-Hodgkin’s Lymphoma

Yang

et al. 2022

Front. Oncol.

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“…Overall, patients with ALCL have inferior EFS compared to the other three types. 1,30,43 Besides, we found that age, sex, and BM involvement did not affect survival, but CNS involvement, advanced stage, and intermediate/high risk predicted inferior survival in pediatric NHL. Similarly, a report from BFM Group study NHL-BFM95 (n = 505; age range, 1.4-19.7 years) revealed that CNS-positive patients had remarkably lower 3-year EFS compared to the whole group (69% vs. 89%), and that stage and risk were adversely associated with 3-year EFS.…”

Section: Discussionmentioning

confidence: 67%

“…Generally, others have reported similar clinical characteristics of pediatric NHL in both white and Asian population. 1,[27][28][29][30][31] Overall, the patients responded well to the chemotherapy regimens at our center. The rates of CR (86.1%), 5-year EFS (74.2%) and OS (85.7%) rate in the whole group were comparable to that of different working groups.…”

Section: Discussionmentioning

confidence: 78%

“…stage III) were associated with poor outcomes (P < 0.05). 30 More recently, Choeyprasert et al identified advanced disease stage as a significant poor prognostic factor for 5-year EFS of pediatric NHL in Thailand. 29 We are aware of the limitations of our study, given the retrospective nature and relatively small sample size enrolled for analyzing the influence of MTHFR on the survival of pediatric NHL.…”

Section: Discussionmentioning

confidence: 99%

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Influence of MTHFR C677T and A1298C polymorphisms on the survival of pediatric patients with non-Hodgkin lymphoma

Zhu¹,

Wei²,

Zhu³

et al. 2020

Preprint

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Objective: We investigated the influence of methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms on the survival of pediatric non-Hodgkin lymphoma (NHL) cases in south China treated with the modified Berlin-Frankfurt-Münster 95 protocol. Methods: We reviewed the medical records of 374 patients newly diagnosed at our center between 2014 and 2020. A subgroup of 158 patients was genotyped based on polymorphisms C677T and A1298C. Results: Overall, there were 283 male (75.7%) and 91 female patients (24.3%); the median age was 9 years (range, 1-18 years). The tumor types included Burkitt lymphoma (BL; n = 180), lymphoblastic lymphoma (LBL; n = 95), anaplastic large cell lymphoma (ALCL; n = 64), and diffuse large B cell lymphoma (DLBCL; n = 35). At diagnosis, 327 patients (87.4%) had advanced-stage disease; 159 (42.5%) and 152 patients (40.6%) were stratified into the intermediate-and high-risk group, respectively. Seventy (18.7%) and 36 cases (9.6%) had bone marrow and central nervous system (CNS) involvement, respectively. The median follow-up time was 28.5 months (range, 1-76 months); complete remission rate, estimated 5-year event-free survival, and 5-year overall survival rate was 86.1%, 74.2%, and 85.7%, respectively. The C677T variant allele was correlated with favorable survival in BL/DLBCL, while ALCL, CNS involvement, advanced stage, and intermediate/high risk were associated with poor survival in NHL. Conclusion: Analysis of the C677T polymorphism could be used for survival prediction and potential risk stratification for further treatment protocols for Chinese pediatric NHL. Further larger studies are needed to verify the clinical value of the C677T polymorphism.

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“…Endemic Burkitt’s lymphoma (eBL) is a B-cell tumor and the most common cancer amongst children from malaria-endemic regions of Sub-Saharan Africa, Asia, and South America [ 1 – 4 ]. Endemic BL has a greater than 90% association with Epstein Barr virus (EBV) infection [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya

et al. 2023

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Background Epstein Barr virus (EBV)-associated endemic Burkitt’s Lymphoma pediatric cancer is associated with morbidity and mortality among children resident in holoendemic Plasmodium falciparum regions in western Kenya. P. falciparum exerts strong selection pressure on sickle cell trait (SCT), alpha thalassemia (-α3.7/αα), glucose-6-phosphate dehydrogenase (G6PD), and merozoite surface protein 2 (MSP-2) variants (FC27, 3D7) that confer reduced malarial disease severity. The current study tested the hypothesis that SCT, (-α3.7/αα), G6PD mutation and (MSP-2) variants (FC27, 3D7) are associated with an early age of EBV acquisition. Methods Data on infant EBV infection status (< 6 and ≥ 6–12 months of age) was abstracted from a previous longitudinal study. Archived infant DNA (n = 81) and mothers DNA (n = 70) samples were used for genotyping hemoglobinopathies and MSP-2. The presence of MSP-2 genotypes in maternal DNA samples was used to indicate infant in-utero malarial exposure. Genetic variants were determined by TaqMan assays or standard PCR. Group differences were determined by Chi-square or Fisher’s analysis. Bivariate regression modeling was used to determine the relationship between the carriage of genetic variants and EBV acquisition. Results EBV acquisition for infants < 6 months was not associated with -α3.7/αα (OR = 1.824, P = 0.354), SCT (OR = 0.897, P = 0.881), or G6PD [Viangchan (871G > A)/Chinese (1024 C > T) (OR = 2.614, P = 0.212)] and [Union (1360 C > T)/Kaiping (1388G > A) (OR = 0.321, P = 0.295)]. There was no relationship between EBV acquisition and in-utero exposure to either FC27 (OR = 0.922, P = 0.914) or 3D7 (OR = 0.933, P = 0.921). In addition, EBV acquisition in infants ≥ 6–12 months also showed no association with -α3.7/αα (OR = 0.681, P = 0.442), SCT (OR = 0.513, P = 0.305), G6PD [(Viangchan (871G > A)/Chinese (1024 C > T) (OR = 0.640, P = 0.677)], [Mahidol (487G > A)/Coimbra (592 C > T) (OR = 0.948, P = 0.940)], [(Union (1360 C > T)/Kaiping (1388G > A) (OR = 1.221, P = 0.768)], African A (OR = 0.278, P = 0.257)], or in utero exposure to either FC27 (OR = 0.780, P = 0.662) or 3D7 (OR = 0.549, P = 0.241). Conclusion Although hemoglobinopathies (-α3.7/αα, SCT, and G6PD mutations) and in-utero exposure to MSP-2 were not associated with EBV acquisition in infants 0–12 months, novel G6PD variants were discovered in the population from western Kenya. To establish that the known and novel hemoglobinopathies, and in utero MSP-2 exposure do not confer susceptibility to EBV, future studies with larger sample sizes from multiple sites adopting genome-wide analysis are required.

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Clinical Characteristics and Treatment Outcomes of Pediatric Patients with Non-Hodgkin Lymphoma in East Asia

Cited by 7 publications

References 23 publications

iTRAQ-Based Proteomic Analysis Reveals Potential Serum Biomarkers for Pediatric Non-Hodgkin’s Lymphoma

iTRAQ-Based Proteomic Analysis Reveals Potential Serum Biomarkers for Pediatric Non-Hodgkin’s Lymphoma

Influence of MTHFR C677T and A1298C polymorphisms on the survival of pediatric patients with non-Hodgkin lymphoma

Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya

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