Real-World Data of Outcome of Patients with Newly Diagnosed Bronchial-Associated Lymphoid Tissue Lymphoma: A Multi-Center Retrospective Analysis with Long-Term Survivors

Abstract

Introduction Extranodal marginal-zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) is an indolent type of non-Hodgkin's lymphoma. Although the lung is the second most common site, it accounts for less than 1% of all lymphomas. Extranodal MZL of MALT type of the lungs originates from bronchial-associated lymphoid tissue (BALT) and is clinically referred to as “BALT lymphoma” or “BALToma”. The indolent nature of BALTomas results in none or mild symptoms and their slow growth pattern allows for various treatment approaches. Depending on the case, active surveillance may be considered, while others may benefit from surgery, radiotherapy or chemotherapy. Despite some existing reviews on this lymphoma, comprehensive characterization of optimal management and prognostic factors remains inadequately defined. Limited case reports and small-scale retrospective data analyses have been conducted, but the number of patients included in these studies was highly restricted. In this study, we conducted a retrospective analysis of clinical data from 67 BALToma patients in South Korea. Methods 67 patients were included in our analysis, all of whom were diagnosed with BALToma between September 1996 and January 2023 at three institutions in South Korea. The criteria for case inclusion was histologically confirmed diagnosis of extranodal MZL of pulmonary origin in accordance with WHO classifications, and availability of clinical data. Extranodal MZL was diagnosed based on WHO classifications, along with the findings from immunohistochemical staining for CD20 and CD3. If needed, CD5, CD10, CD23, cyclin D1, BCL6, and Ki-67 was also stained. Gene rearrangement studies targeting the IgH gene were conducted using PCR analysis. Patients were treated according to the stage and location of the disease. The patients were analyzed into two groups; observation or localized treatment and systemic chemotherapy. Localized treatment included surgery or radiotherapy. Systemic chemotherapy regimens used were mainly (R)-CVP and (R)-CHOP. Baseline characteristics was analyzed with Fisher's exact test. Overall survival (OS) and Progression Free Survival (PFS) were estimated using the Kaplan-Meier method. PFS was calculated from the date of diagnosis to the date on which progression was noted, the date of the last follow-up, or the date of death. OS was measured from the date of diagnosis to the date of death or the last follow-up visit. Survival rates were compared for statistical differences via Generalized Wilcoxon analyses. Prognostic factor analysis and hazard ratio was calculated using univariate and multivariate Cox Regression method. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. All data was analyzed using SPSS Statistics for Windows, Version 27.0. Results The clinical characteristics of patients according to treatment modality was analyzed (Table 1). Gender, age, performance status was not significantly different between each group. Notably, involvement of single or multiple lobe (p=0.045), involvement of bilateral lung (p<0.001), nodal involvement (p=0.033), and involvement of extrapulmonary organ (p=0.010) was significantly different between each group. The PFS and OS according to treatment method are provided in Figure 1 and 2. 10-year PFS for observation or localized treatment was 78.7% whereas chemotherapy was 56.9% (p=0.044). 10-year OS for observation or localized treatment was 100%, whereas chemotherapy was 71.7% (p=0.016). The prognostic factors for progression of disease were significant only for the involvement of extrapulmonary organ in both univariate and multivariate (hazard ratio 3.615, p=0.023) analysis (Table 2). Prognostic factor analysis for overall survival did not yield any significant result. Conclusion This study concludes that the most important prognostic factor for the progression of disease is the involvement of extrapulmonary organ. This study implies that the feasibility of simply monitoring patients whose disease is confined exclusively to the lung is a viable strategy. However, in the case of extrapulmonary involvement, the implementation of systemic chemotherapy ought to be deliberated. Given the heightened potential for disease progression, this underscores the necessity for meticulous consideration during the development of therapeutic plans.