Extranodal site of diffuse large B‐cell lymphoma and the risk of R‐CHOP chemotherapy resistance and early relapse

Abstract

Background About 20%‐30% of diffuse large B‐cell lymphoma (DLBCL) patients experience early disease progression despite R‐CHOP chemotherapy treatment. Revised international prognostic index (R‐IPI) score could risk stratify DLBCL patients but does not identify exactly which patient will be resistant to R‐CHOP therapy or experience early relapse. Aims of the Study To analyse pre‐treatment clinical features of DLBCL patients that are predictive of R‐CHOP therapy resistance and early disease relapse after R‐CHOP therapy treatment. Methods Used to Conduct the Study A total of 698 lymphoma patients were screened and 134 R‐CHOP‐treated DLBCL patients were included. The Lugano 2014 criteria was applied for assessment of treatment response. DLBCL patients were divided into R‐CHOP resistance/early relapse group and R‐CHOP sensitive/late relapse group. Results of the Study 81 of 134 (60%) were R‐CHOP sensitive/late relapse, while 53 (40%) were R‐CHOP resistance/early relapse. The median follow‐up period was 59 months ± standard error 3.6. Five‐year overall survival rate of R‐CHOP resistance/early relapse group was 2.1%, while it was 89% for RCHOP sensitive/late relapse group. Having more than one extranodal site of DLBCL disease is an independent risk factor for R‐CHOP resistance/early relapse [odds ratio = 5.268 (1.888‐14.702), P = .002]. The commonest extranodal sites were head and neck, gastrointestinal tract, respiratory system, vertebra and bones. Advanced age (>60 years), advanced disease stage (lll‐lV), raised pre‐treatment lactate dehydrogenase level, bone marrow involvement of DLBCL disease high Eastern Cooperative Oncology Group status (2‐4) and high R‐IPI score (3‐5) showed no significant association with R‐CHOP therapy resistance/early disease relapse (multivariate analysis: P > .05). Conclusion and Clinical Implications DLBCL patients with more than one extranodal site are 5.268 times more likely to be R‐CHOP therapy resistance or experience early disease relapse after R‐CHOP therapy. Therefore, correlative studies are warranted in DLBCL patients with more than one extranodal site of disease to explore possible underlying mechanisms of chemoresistance.

Modified Stage Grouping of Diffuse Large B-Cell Lymphoma Involving the Same Side of the Diaphragm in the Rituximab Era

“…Taking these findings into consideration, among patients whose disease extent was limited to the same side of the diaphragm but were not classified as stage 1 DLBCL, the following subgroups were classified as “modified stage II” disease: 1) patients with nodal lesions only, 2) patients with single extranodal lesion that was contiguous to the nodal lesion, and 3) patients with single extranodal lesion that was non-contiguous to the nodal lesion. In contrast, patients with ≥2 extranodal involvement showed significantly inferior PFS and OS compared with the modified stage II DLBCL patients in this study, which was consistent with previous studies ( 2 , 9 ). These results suggest that the amount of extranodal involvement, rather than the presence of extranodal involvement itself or the anatomic contiguity of the lesion, is a more important prognostic factor for patients with DLBCL on the same side of the diaphragm.…”

“…Previous retrospective studies reported poorer survival outcomes of extranodal disease compared with nodal disease among patients with stage 1 DLBCL or in the overall DLBCL population ( 9 – 11 ). However, few studies have reported the prognostic implication of extranodal disease among patients with Ann Arbor stage 2 DLBCL or patients with disease involving the same side of the diaphragm.…”

Programmed death-ligand 1 expression in diffuse large B-cell lymphoma is associated with poor prognosis

“…9 In fact, patients with poor response to R-CHOP have a 1-year overall survival. 10 The expression of programmed death-ligand 1 protein (PD-L1) is upregulated in tumors. 11,12 PD-L1 binding to the PD-1 receptor on immune cells results in tolerance for tumor antigens and the down regulation of T-cells.…”

Diffuse Large B-Cell Lymphoma of the Left Upper Extremity Mimicking a Sarcoma

“…The median age for DLBCL is between the sixth and seventh decade of life. Diffuse Large B-cell Lymphomas can arise in an extranodal organ in up to 30% of cases with the most common sites being gastrointestinal tract, skin and soft tissue, bone or genitourinary tract [ 2 ]. DLBCLs are rare in the soft tissue of the upper extremity.…”