Development and validation of novel models based on clonality immunoglobulin gene rearrangement for evaluation of bone marrow involvement and prognostic prediction in patients with diffuse large B-cell Lymphoma: a multicenter retrospective study

IntroductionBone marrow involvement (BMI) is a poor prognostic factor in diffuse large B cell lymphoma (DLBCL), and accurate evaluation of BMI is crucial for determining stages and prognosis. This study aimed to identify the most effective examinations for evaluating BMI in DLBCL, including positron...

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Main Authors: Zelin Liu, Qianping Li, Ruiqi Liu, Yangyang Ding, Ya Liao, Linhui Hu, Lianfang Pu, Chunhua Zhu, Shenghui Zhang, Shudao Xiong
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1547056/full
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author Zelin Liu
Zelin Liu
Qianping Li
Qianping Li
Ruiqi Liu
Yangyang Ding
Yangyang Ding
Ya Liao
Ya Liao
Linhui Hu
Linhui Hu
Lianfang Pu
Lianfang Pu
Chunhua Zhu
Shenghui Zhang
Shenghui Zhang
Shudao Xiong
Shudao Xiong
Shudao Xiong
author_facet Zelin Liu
Zelin Liu
Qianping Li
Qianping Li
Ruiqi Liu
Yangyang Ding
Yangyang Ding
Ya Liao
Ya Liao
Linhui Hu
Linhui Hu
Lianfang Pu
Lianfang Pu
Chunhua Zhu
Shenghui Zhang
Shenghui Zhang
Shudao Xiong
Shudao Xiong
Shudao Xiong
author_sort Zelin Liu
collection DOAJ
description IntroductionBone marrow involvement (BMI) is a poor prognostic factor in diffuse large B cell lymphoma (DLBCL), and accurate evaluation of BMI is crucial for determining stages and prognosis. This study aimed to identify the most effective examinations for evaluating BMI in DLBCL, including positron emission tomography-computed tomography (PET/CT), immunoglobulin gene rearrangement (IGR), flow cytometry (FCM), bone marrow cytology (BMC) and bone marrow biopsy pathology (BMB), and to further explore its prognostic significance in DLBCL patients.MethodsThis retrospective study included 364 newly diagnosed DLBCL patients, all of whom underwent PET/CT, IGR, FCM, BMC, and BMB at diagnosis. Survival outcomes were analyzed via Kaplan-Meier and Cox regression models. Novel prognostic models incorporating combined IGR and BMB results were developed in a training cohort.ResultsCompared to other detection methods, Clonal IGR BMI-positive were found the highest rate of 114 patients (31.3%), and IGR BM involvement-positive patients of DLBCL had the worst survival outcomes, especially among patients in stages I to III (P<0.001). Notably, PET/CT existed some limitations in BMI diagnosis, particularly in stage IV patients (P>0.05). Additionally, the combination of IGR and BMB demonstrated superior prognostic predictive capability for the patients in stage IV (PP<0.001). Multivariate analysis further confirmed that double-positive BMI of IGR and BMB was an independent prognostic factors of PFS (P=0.026) and OS (P=0.042). In addition, the novel IPI and NCCN-IPI stratification models were established by incorporating the combination of IGR and BMB in training group. The C-index of novel models were increased when IGR and BMB were supplemented in our cohort.DiscussionOur results suggest that IGR is the most valuable methods for evaluating BMI compared to traditional detection methods. Adding the combination of IGR and BMB to the IPI and NCCN-IPI score may improve their predictive ability. In summary, IGR is essental for evaluation of BMI and provide an ideal method for disease staging and risk stratification in DLBCL patients in the rituximab era.
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spelling doaj-art-c7409d7d333348dd8e942e3d2def5c882025-08-20T02:28:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15470561547056Development and validation of novel models based on clonality immunoglobulin gene rearrangement for evaluation of bone marrow involvement and prognostic prediction in patients with diffuse large B-cell Lymphoma: a multicenter retrospective studyZelin Liu0Zelin Liu1Qianping Li2Qianping Li3Ruiqi Liu4Yangyang Ding5Yangyang Ding6Ya Liao7Ya Liao8Linhui Hu9Linhui Hu10Lianfang Pu11Lianfang Pu12Chunhua Zhu13Shenghui Zhang14Shenghui Zhang15Shudao Xiong16Shudao Xiong17Shudao Xiong18Hematological Lab, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaInstitute of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaHematological Lab, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaHematological Lab, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaHematological Lab, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaHematological Lab, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaAir Force Health Care Center for Special Services, Hangzhou, Zhejiang, ChinaInstitute of Hematology, Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaHematological Lab, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaResearch Center for Translational Medicine, The Second Hospital of Anhui Medical University, Hefei, Anhui, ChinaIntroductionBone marrow involvement (BMI) is a poor prognostic factor in diffuse large B cell lymphoma (DLBCL), and accurate evaluation of BMI is crucial for determining stages and prognosis. This study aimed to identify the most effective examinations for evaluating BMI in DLBCL, including positron emission tomography-computed tomography (PET/CT), immunoglobulin gene rearrangement (IGR), flow cytometry (FCM), bone marrow cytology (BMC) and bone marrow biopsy pathology (BMB), and to further explore its prognostic significance in DLBCL patients.MethodsThis retrospective study included 364 newly diagnosed DLBCL patients, all of whom underwent PET/CT, IGR, FCM, BMC, and BMB at diagnosis. Survival outcomes were analyzed via Kaplan-Meier and Cox regression models. Novel prognostic models incorporating combined IGR and BMB results were developed in a training cohort.ResultsCompared to other detection methods, Clonal IGR BMI-positive were found the highest rate of 114 patients (31.3%), and IGR BM involvement-positive patients of DLBCL had the worst survival outcomes, especially among patients in stages I to III (P<0.001). Notably, PET/CT existed some limitations in BMI diagnosis, particularly in stage IV patients (P>0.05). Additionally, the combination of IGR and BMB demonstrated superior prognostic predictive capability for the patients in stage IV (PP<0.001). Multivariate analysis further confirmed that double-positive BMI of IGR and BMB was an independent prognostic factors of PFS (P=0.026) and OS (P=0.042). In addition, the novel IPI and NCCN-IPI stratification models were established by incorporating the combination of IGR and BMB in training group. The C-index of novel models were increased when IGR and BMB were supplemented in our cohort.DiscussionOur results suggest that IGR is the most valuable methods for evaluating BMI compared to traditional detection methods. Adding the combination of IGR and BMB to the IPI and NCCN-IPI score may improve their predictive ability. In summary, IGR is essental for evaluation of BMI and provide an ideal method for disease staging and risk stratification in DLBCL patients in the rituximab era.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1547056/fulldiffuse large B cell lymphomabone marrow involvementimmunoglobulin gene rearrangementpositron emission tomography-computed tomographyflow cytometrybone marrow cytology
spellingShingle Zelin Liu
Zelin Liu
Qianping Li
Qianping Li
Ruiqi Liu
Yangyang Ding
Yangyang Ding
Ya Liao
Ya Liao
Linhui Hu
Linhui Hu
Lianfang Pu
Lianfang Pu
Chunhua Zhu
Shenghui Zhang
Shenghui Zhang
Shudao Xiong
Shudao Xiong
Shudao Xiong
Development and validation of novel models based on clonality immunoglobulin gene rearrangement for evaluation of bone marrow involvement and prognostic prediction in patients with diffuse large B-cell Lymphoma: a multicenter retrospective study
Frontiers in Immunology
diffuse large B cell lymphoma
bone marrow involvement
immunoglobulin gene rearrangement
positron emission tomography-computed tomography
flow cytometry
bone marrow cytology
title Development and validation of novel models based on clonality immunoglobulin gene rearrangement for evaluation of bone marrow involvement and prognostic prediction in patients with diffuse large B-cell Lymphoma: a multicenter retrospective study
title_full Development and validation of novel models based on clonality immunoglobulin gene rearrangement for evaluation of bone marrow involvement and prognostic prediction in patients with diffuse large B-cell Lymphoma: a multicenter retrospective study
title_fullStr Development and validation of novel models based on clonality immunoglobulin gene rearrangement for evaluation of bone marrow involvement and prognostic prediction in patients with diffuse large B-cell Lymphoma: a multicenter retrospective study
title_full_unstemmed Development and validation of novel models based on clonality immunoglobulin gene rearrangement for evaluation of bone marrow involvement and prognostic prediction in patients with diffuse large B-cell Lymphoma: a multicenter retrospective study
title_short Development and validation of novel models based on clonality immunoglobulin gene rearrangement for evaluation of bone marrow involvement and prognostic prediction in patients with diffuse large B-cell Lymphoma: a multicenter retrospective study
title_sort development and validation of novel models based on clonality immunoglobulin gene rearrangement for evaluation of bone marrow involvement and prognostic prediction in patients with diffuse large b cell lymphoma a multicenter retrospective study
topic diffuse large B cell lymphoma
bone marrow involvement
immunoglobulin gene rearrangement
positron emission tomography-computed tomography
flow cytometry
bone marrow cytology
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1547056/full
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