Abstract
Background
This study aims to investigate the treatment outcomes and identify risk factors influencing complete remission (CR) and relapse in patients with gastric MALT lymphoma across different treatment modalities.
Methods
Three-hundred and ninety-eight patients with gastric MALT lymphoma were followed up for at least 48 weeks over 15 years in five tertiary hospitals in regions with high prevalence of Helicobacter pylori (H. pylori) infection. A retrospective review was performed using medical records.
Results
A total of 398 patients were included, with a mean age at diagnosis of 55.5 ± 12.2 years and 176 (44.2%) were male. H. pylori infection was identified in 293 patients (73.6%), and 363 (91.2%) were diagnosed with stage IE. Significant differences in age, sex, and stage at diagnosis were observed between H. pylori-positive (HPP) and H. pylori-negative groups (HPN, all P < 0.05). In the HPP group, most patients underwent eradication therapy (98.9%), whereas 77.3% of HPN patients received eradication therapy, often combined with radiotherapy or chemotherapy. CR rate was 97.0%, with 98.3% in HPP and 93.3% in HPN (P = 0.018). During a median follow-up of 179 weeks, relapse occurred in 8.3% of patients, with 7.9% in HPP and 10.2% in HPN, respectively. Non-IE Modified Ann Arbor Stage (HR, 2.4; 95% CI, 1.0–5.5; P = 0.044), presence of lymphadenopathy (HR, 1.9; 95% CI, 1.2–3.1; P = 0.010), and lesions in multiple locations (HR, 2.1; 95% CI, 1.0 ~ 4.2; P = 0.037) at diagnosis correlated with a higher cumulative incidence of relapse (CIR). Multivariate Cox regression analysis showed that Non-IE Modified Ann Arbor Stage (aHR, 1.9; 95% CI, 1.2‒2.9; P = 0.004) and presence of lymphadenopathy (aHR, 1.5; 95% CI, 1.0‒2.3; P = 0.037) remained significantly correlated with higher CIR.
Conclusions
Patients with gastric MALT lymphoma generally have a favorable prognosis, and H. pylori eradication can lead to CR, even in H. pylori-negative MALT lymphoma cases. Accurate staging at diagnosis is essential for optimal management, as disease stage and the presence of lymphadenopathy are key predictors of relapse.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12876-026-04699-4.
Keywords: Mucosa-associated lymphoid tissue lymphoma, Helicobacter pylori, eradication, survival analysis
Background
Primary gastric lymphomas (PGLs) are a group of lymphoproliferative neoplasms characterized by clinical and molecular heterogeneity [1]. Although rare, PGL tumor accounts for < 15% of gastric malignancies and approximately 2% of all lymphomas. Among these, mucosa-associated lymphoid tissue (MALT) lymphoma represents up to 50% of PGLs [2]. MALT lymphoma is characterized by a variable number of lymphoepithelial lesions, wherein tumor cells infiltrate and partially obstruct mucosal glands [2]. In a national cancer-screening program conducted at a tertiary healthcare center in South Korea, the overall PGL detection rate was reported as 0.49 per 1,000 screenings, with MALT lymphoma constituting 98.1% of PGL cases [3]. Numerous studies report a correlation between various infections, including Helicobacter pylori (H. pylori), human T-cell leukemia virus type 1, human immunodeficiency virus, Epstein–Barr virus, hepatitis B virus, and hepatitis C virus, and the pathogenesis of PGLs [4, 5]. H. pylori infection is strongly associated with MALT lymphoma, and its eradication therapy induces remission [6]. A previous study reports that early-stage gastric MALT lymphoma could achieve a complete remission (CR) rate of 77.5% with H. pylori eradication therapy [7]. Nevertheless, a significant proportion of patients with gastric MALT lymphoma, ranging from 17% to 61%, do not respond to H. pylori eradication treatment. No current consensus exists regarding the optimal treatment for this group [8]. Identified risk factors for non-responsiveness to H. pylori eradication include non-superficial type endoscopic finding, tumor location, multiple lesions, presence of the t(11,18) translocation, advanced stage, old age, and status of the H. pylori infection [9–11]. However, owing to the heterogeneity of treatment regimens, H. pylori infection rates, and antibiotic resistance rates associated with H. pylori eradication, treatment outcomes across studies are inconsistent [12]. Therefore, this study aims to investigate the treatment outcomes in patients with gastric MALT lymphoma to identify prognostic factors influencing CR and relapse in regions characterized by high H. pylori infection rates and antibiotic resistance to H. pylori eradication.
Methods
Patient selection
In total, 488 patients diagnosed with gastric MALT lymphoma between 2004 and 2022 at five tertiary hospitals in Honam Province, South Korea, were included in this study. Of these, 85 patients were excluded owing to insufficient follow-up data spanning < 48 weeks. Of the remaining 403 patients, an additional five patients were excluded because their post-treatment examinations lacked biopsy-confirmed assessment of disease remission. Ultimately, 398 patients were included in the final analysis and were divided into two groups based on their H. pylori infection status: the H. pylori-positive (HPP) and H. pylori-negative groups (HPN, Fig. 1). H. pylori infection status was evaluated via the implementation of diverse diagnostic techniques, including histology, rapid urease test, urea breath test (UBT), serologic testing, and H. pylori polymerase chain reaction (PCR). Patients were classified as HPP if at least one of these diagnostic tests returned a positive result, while those who did not meet the HPP criteria for inclusion were classified as HPN. Electronic medical records of patients were extracted, and a retrospective review was performed using the medical records.
Fig. 1.
Flow chart of this study
Diagnosis and staging
Histologic examination of suspected lesions was conducted using upper endoscopy performed by an experienced endoscopist. Tissue specimens were then assessed by a trained pathologist, followed by diagnoses that were confirmed based on the World Health Organization classification criteria. Lesions with a Wotherspoon score of 5 were diagnosed as MALT lymphoma. Lesions with scores of 3 and 4 were diagnosed as MALT lymphoma when B-cell monoclonality was demonstrated via analysis of immunoglobulin heavy chain tran rearrangements using PCR [13, 14]. To confirm the presence of lymphadenopathy (LAP) at the time of diagnosis, all patients underwent computed tomography scan or endoscopic ultrasonography. The staging was conducted using the modified Ann Arbor staging system [15, 16].
Endoscopic findings
Gross findings were classified into three types based on endoscopic features: superficial—erosive, discolored, cobblestone, flat-depressed, and fold-thickening—ulcerative, and mass-forming types—subepithelial tumor-like morphology and polypoid features. Additionally, the location and number of lesions were examined.
Treatment and response assessment
Detailed information on treatments, including H. pylori eradication therapy, radiotherapy (RT), or chemotherapy, was collected from medical records. For patients who received H. pylori eradication therapy, information regarding UBT, Campylobacter like organism (CLO) test, or PCR analysis of endoscopic biopsy specimens was collected to confirm eradication success.
Post-treatment evaluation of lymphoma regression was conducted 6 months after completing treatment using endoscopy. Follow-up assessments were subsequently conducted every 3–6 months until CR of the lymphoma was achieved.
Treatment response was assessed based on the histological grading system proposed by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). Complete response was defined as improvement in endoscopic findings and negative histologic results in at least two subsequent follow-up investigations. Relapse was defined as persistent histologically confirmed lymphoma after CR has been documented.
Relapse-free survival was defined as the time from the date of CR achievement to relapse, last follow-up, or death. Patients who did not meet endpoints were censored at the date of last follow-up or death if it was a competing risk.
Statistical analysis
To analyze the differences between the two groups, Chi-square and Fisher’s exact tests were employed. Additionally, logistic regression models were employed to identify factors associated with clinical remission, with 95% confidence intervals (CIs) calculated for the results. The time required to achieve CR or relapse was estimated and compared using the Kaplan–Meier method. Survival rates were also calculated using the Kaplan–Meier method, and the resulting survival curves were generated. Univariate analysis was conducted using log-rank tests, while multivariate analysis was conducted using the Cox proportional hazard model. All statistical analyses were performed using SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA), and a p-value of < 0.05 was considered statistically significant.
Results
Baseline characteristics of the 398 patients
Table 1 shows the differences in the baseline clinical characteristics. The mean age of the cohort was 55.53 years (interquartile range (IQR), 47.75‒65.00 years), with 176 of them being male. Lesions were predominantly distributed in the distal third (196 patients, 49.2%). Endoscopic findings showed a predominance of superficial-type morphology (239 patients, 60.1%), followed by ulcerative-type (139 patients, 34.9%) and mass-forming-type lesions (20 patients, 5.0%). In total, 229 patients (57.5%) had isolated lesions, while 169 patients (42.5%) had multiple lesions. No statistically significant differences in macroscopic findings were observed between HPP and HPN, as shown in Table 2. Endoscopic findings of background mucosal change were also comparable according to H. pylori status. (all P > 0.05). In HPN, endoscopic findings suggestive of non-H. pylori Helicobacter (NHPH) infection included white‑marbled mucosa in 31.1% of patients, crack‑like changes in 29.1% of patients, or nodular gastritis–like appearance in 3.6% of patients. Thirty-six patients exhibited lymphadenopathy, and 366 (92.0%) were diagnosed with stage IE disease at the time of diagnosis. Regarding H. pylori infection status, 293 and 105 patients were classified as HPP and HPN, respectively (Table 2). The mean age of HPP (54.7 years) was lower than that of HPN (57.8 years, P = 0.024). The HPN was more inclined to exhibit advanced stage (Stage IIE or higher, P for trend < 0.001).
Table 1.
Baseline demographics and clinical characteristics of 398 patients with gastric MALT lymphoma
| Variables | |
|---|---|
| Age, years, mean ± SD | 55.53 ± 12.22 |
| Male, n (%) | 176 (44.2) |
| H. pylori-positive, n (%) | 293 (73.6) |
| H. pylori-negative, n (%) | 105 (26.4) |
| Location, n (%) | |
| Upper third | 89 (22.4) |
| Mid third | 110 (27.6) |
| Distal third | 196 (49.2) |
| Macroscopic findings, n (%) | |
| Superficial | 239 (60.1) |
| Ulcerative | 139 (34.9) |
| Mass-forming | 20 (5.0) |
| Lesion, n (%) | |
| Isolated | 229 (57.5) |
| Multiple | 169 (42.5) |
| Lymphadenopathy (+), n (%) | 36 (9.0) |
| Stage, n (%) | |
| IE | 366 (91.96) |
| IIE | 16 (4.02) |
| IIIE | 6 (1.51) |
| IV | 10 (2.51) |
H. pylori Helicobacter pylori,SD Standard deviation, Stage Ann-Arbor stage, MALT mucosa-associated lymphoid tissue
Table 2.
Baseline demographics and clinical characteristics between H. pylori-positive and H. pylori-negative groups
| Variables | H. pylori (+), n = 293 | H. pylori (-), n = 105 | P-value |
|---|---|---|---|
| Age, mean ± SD | 54.70 ± 12.45 | 57.83 ± 11.28 | 0.024 |
| Male, n (%) | 118(40.3) | 58(55.2) | 0.008 |
| Location, n (%) | 0.610 | ||
| Upper third | 61 (20.8) | 28 (26.7) | |
| Mid third | 84 (28.7) | 26 (24.8) | |
| Distal third | 145 (49.5) | 51 (48.6) | |
| Macroscopic findings, n (%) | 0.347 | ||
| Superficial | 169 (57.7) | 70 (66.7) | |
| Ulcerative | 107 (36.5) | 32 (30.5) | |
| Mass-forming | 17 (5.8) | 3 (2.9) | |
| Lesion, n (%) | 0.924 | ||
| Isolated, n (%) | 169 (57.7) | 60 (57.1) | |
| Multiple, n (%) | 124 (42.3) | 45 (42.9) | |
| Lymphadenopathy, n (%) | 20 (6.8) | 16 (15.2) | 0.010 |
| Stage, n (%) | < 0.001 | ||
| IE | 277 (94.5) | 89 (84.8) | |
| IIE | 13 (4.4) | 3 (2.9) | |
| III | 1 (0.3) | 5 (4.8) | |
| IV | 2 (0.7) | 8 (7.6) |
H. pylori Helicobacter pylori, SD Standard deviation, Stage Ann-Arbor stage
Treatment outcomes in patients with H. pylori infection
In the HPP group, 99.0% (290/293), 25.3% (74/293), and 6.1% (18/293) of patients received H. pylori eradication therapy, RT, and chemotherapy, respectively. Three patients did not receive eradication therapy as the initial treatment following a shared decision-making process: two patients were diagnosed with Stage IV disease and underwent systemic chemotherapy, and one patient received radiotherapy because endoscopic ultrasonography revealed submucosal and proper muscle invasion, raising concerns about the limited efficacy of eradication therapy. CR was achieved in 98.3% (288/293) of the HPP group. The median time to achieve a CR was 133 days (IQR, 83‒262 days). H. pylori eradication was successful in 86.9% (252/290) of patients.
In the HPP group, no significant clinical or endoscopic factors were associated with eradication failure, as subgroup analysis showed no differences in sex, disease stage, or gross endoscopic features between eradication responders and non-responders (Supplementary Table 1). Among the 252 patients with successful H. pylori eradication, 56 underwent additional RT. Among the 38 patients with H. pylori eradication failure, 2 and 17 patients underwent chemotherapy and RT, respectively. No significant differences were observed in CR between patients with successful H. pylori eradication (247/252, 98.0%) and those without a successful one (38/38, 100%, P = 0.999). Among patients with successful H. pylori eradication, no significant difference in CR was observed between patients with additional RT (55/56, 98.0%) and those without RT (192/196, 98.0%, P = 0.999, Fig. 2). Thirty-eight patients with failed H. pylori eradication achieved CR, and 21 patients achieved CR without requiring additional RT or chemotherapy. The median time to CR for these 21 patients was 97.00 days (IQR, 66.00–331.00 days).
Fig. 2.
Treatment outcomes of H. pylori positive group. H. pylori, Helicobacter pylori; CR, complete remission
Treatment outcomes in patients without H. pylori infection
In the HPN group, 73.3% (77/105) of patients received H. pylori eradication therapy. Of these, 39, 33, 3, and 2 patients received only H. pylori eradication therapy, H. pylori eradication + RT, H. pylori eradication + chemotherapy, and H. pylori eradication + chemotherapy + RT, respectively. The overall CR rate in the HPN group was 93.3% (98/105). The median time to achieve a CR was 171 days (IQR, 99‒379 days). Among the 77 patients who underwent H. pylori eradication, CR was achieved in 46.8% (36/77) of those who received H. pylori eradication alone. No significant differences were observed between eradication responders and non-responders with respect to age, tumor location, endoscopic findings, disease stage, or the presence of LAP (Supplementary Table 2). Additional treatments were subsequently administered in 38 patients, resulting in a CR rate of 92.1% (35/38) after combined therapy. Among the 28 patients who did not receive H. pylori eradication, 7, 14, and 7 patients received chemotherapy, RT, and chemotherapy + RT, respectively. CR was achieved in 96.4% (27/28) of the patients (Fig. 3).
Fig. 3.
Treatment outcomes of H. pylori negative group. H. pylori, Helicobacter pylori; CR, complete remission
Factors associated with remission failure or relapse
Overall CR rate was 97.0% (386/398). CR rate was significantly higher in HPP [98.3% (288/293)] than in HPN [93.3% (98/105), P = 0.018]. Conversely, no significant differences were observed in age, location and endoscopic finding of tumor, stage, and presence of LAP.
During a median follow-up period of 179 weeks (IQR, 94‒269 weeks), relapse occurred in 32 of the 386 patients who achieved CR [7.9% (23/291) in HPP and 10.2% (10/98) in HPN]. The median time to relapse was 96 weeks (IQR, 41‒189 weeks). Univariate analysis showed that patients with Non-IE Modified Ann Arbor Stage (hazard ratio (HR), 2.316, 95% CI, 0.995‒5.390, P = 0.051), presence of LAP (HR, 2.236; 95% CI, and 0.964‒5.185; P = 0.061) and lesions in multiple locations (HR, 1.932; 95% CI, 0.959‒3.892; P = 0.065) at the time of diagnosis tended to have lower relapse-free survival with borderline significance (Table 3). Multivariate analysis, adjusted for age, sex, H. pylori infection and multiple lesions, patients with Non-IE Modified Ann Arbor Stage (adjusted HR (aHR), 1.865; 95% CI, 1.220‒2.851; P = 0.004), and presence of LAP (aHR, 1.521; 95% CI, 1.026‒2.254; P = 0.037) showed statistically significant lower relapse-free survival (Table 4). Figure 4a and b show the Kaplan–Meier curves for relapse-free survival.
Table 3.
Factors associated with relapse-free survival in 386 patients with complete remission
| Variables | Relapse | HR | P-values |
|---|---|---|---|
| Age | |||
| <65 yrs. | 20/298 (6.7%) | 1 | |
| ≥ 65 yrs. | 12/88 (13.6%) | 1.880 (0.917‒3.852) | 0.085 |
| H. pylori | |||
| (+) | 22/288 (7.6%) | 1 | |
| (-) | 10/98 (10.2%) | 1.366 (0.646‒2.887) | 0.414 |
| Location | |||
| Mid to lower | 24/299 (8.0%) | 1 | |
| Upper | 8/84 (9.5%) | 1.4 (0.628‒3.118) | 0.411 |
| Macroscopic findings | |||
| Non-mass forming | 28/366 (7.7%) | 1 | |
| Mass forming | 4/20 (20.0%) | 2.079 (0.726‒5.948) | 0.173 |
| Lesion | |||
| Isolated | 14/222 (6.3%) | 1 | |
| Multiple | 18/164 (11.0%) | 1.932 (0.959‒3.892) | 0.065 |
| Lymphadenopathy | |||
| No | 25/352 (7.1%) | 1 | |
| Yes | 7/34 (20.6%) | 2.236 (0.964‒5.185) | 0.061 |
| Stage | |||
| IE | 25/356 (7.0%) | 1 | |
| Non-IIE | 7/30 (23.3%) | 2.316 (0.995‒5.390) | 0.051 |
H. pylori, Helicobacter pylori; Stage Ann-Arbor stage
Table 4.
Multivariate analysis for factors associated with relapse-free survival
| aHR (95%CI) | p-value | |
|---|---|---|
| Lymphadenopathy | 1.521 (1.026 ~ 2.254) | 0.037 |
| Stage Non-IE | 1.865 (1.220 ~ 2.851) | 0.004 |
adjustment for age, sex, status of H. pylori infection, multiple lesions; aHR adjusted hazard ratio, HR hazard ratio, H. pylori Helicobacter pylori
Fig. 4.
Kaplan-Meier curve of relapse free survival. A Presence of LAP showed statistically significant lower relapse-free survival (aHR, 1.521; 95% CI, 1.026‒2.254; P = 0.037) B Non-IE Modified Ann Arbor Stage showed statistically lower relapse-free survival (aHR), 1.865; 95% CI, 1.220‒2.851, P = 0.004)
Discussion
This retrospective study was conducted across five tertiary hospitals in Honam Province, a region with high H. pylori infection rates [17]. It provides real-world clinical experience of patients with gastric MALT lymphoma over a long-term follow-up period, offering valuable insights into the natural treatment outcomes of the disease.
In 1991, Wotherspoon et al. first demonstrated that the histologic features of H. pylori-associated gastritis closely resemble those seen in patients with gastric MALT lymphoma, indicating a high association between gastric MALT lymphoma and H. pylori infection [18, 19]. Subsequently, several clinical and laboratory studies have demonstrated a strong correlation between H. pylori and gastric MALT lymphoma [20–22]. In our study, approximately 74% of patients with gastric MALT lymphoma tested positive for H. pylori infection, while the remaining 26% were HPN. This shows a little higher prevalence of HPN MALT lymphoma compared to those of previous studies [23, 24]. However, a recent nationwide multicenter study in South Korea reports a similar proportion of HPN MALT lymphoma, aligning with our findings [25]. Furthermore, a recent meta-analysis by Xie et al. highlights the increasing global prevalence of HPN gastric MALT lymphoma [26].
Significant differences in the baseline demographics and clinical characteristics were observed between the HPP and HPN groups. The HPN group was older than the HPP group and had a greater proportion of male patients than those of the HPP group. Moreover, the HPN group more frequently presented with LAP and advanced stage at the diagnosis of MALT lymphoma, which is consistent with findings from a previous study [27].
In the HPP group, the CR rate was 98.3%, with a median time to achieve CR of 133 days, which is shorter than that in other studies [28, 29]. Most patients with HPP initially underwent H. pylori eradication, and 98% of them achieved CR with H. pylori eradication alone. These findings align with the results obtained in South Korea and other countries [7, 9, 11, 23, 28, 29]. Among the HPP group, 56 patients underwent additional RT following successful H. pylori eradication, and 98.2% of them achieved CR. This shows that no significant differences in CR were observed compared to those who received H. pylori eradication alone. Our findings suggest that supplementary RT does not provide additional benefits in patients who have achieved H. pylori eradication. Among the 38 patients in the HPP group who did not achieve successful H. pylori eradication, all eventually reached CR. Of these patients, 21 achieved CR without the need for additional RT or chemotherapy. This finding is consistent with that of a previous study, which reports that 95% of the HPP group experiencing H. pylori eradication failure exhibits stable disease when managed with a “watch and wait” strategy [29]. The remission observed in these patients should be interpreted with caution, as it might reflect the indolent or self-limiting course sometimes seen in gastric MALT lymphoma rather than a direct effect of eradiation therapy.
In the HPN group, the overall CR rate was 93.3%, with 46.8% of patients achieving CR via H. pylori eradication alone. Several hypotheses may explain the effectiveness of H. pylori eradication in the HPN group. One hypothesis is the potential involvement of other bacteria or viruses in the pathogenesis of MALT lymphoma. Various pathogens, including Campylobacter jejuni in immunoproliferative small intestinal disease, Borrelia burgdorferi in primary cutaneous B-cell lymphoma, Chlamydophila psittaci in ocular adnexal lymphoma, and hepatitis C virus in splenic marginal zone lymphoma, have been associated with marginal zone B-cell lymphomas [13, 23]. This evidence suggests that similar microorganisms might play a role in gastric MALT lymphoma development. In particular, recent studies demonstrated that some cases of H. pylori-negative gastric MALT lymphoma may be associated with NHPH species, which can colonize the human gastric mucosa and respond to standard eradication regimens. In HPN of this study, endoscopic findings potentially suggestive of NHPH infection were heterogeneous, including white‑marbled mucosa, crack‑like changes, and a nodular gastritis–like appearance [30]. However, NHPH infection could not be definitively confirmed in our study because molecular or detailed microbiologic tests (such as NHPH‑specific PCR, sequencing, or culture) were not routinely performed. This limitation raises the possibility that a subset of HPN cases in our study might have been related to undetected NHPH infection. H. heilmannii-positive gastric MALT lymphoma cases have been reported, with successful CR achieved using eradication therapy [31, 32]. Moreover, clarithromycin, a key component of H. pylori eradication regimens, exhibits significant immunomodulatory effects, including the induction of apoptosis in activated lymphocytes and the suppression of cytokine production. These properties may contribute to the remission of MALT lymphoma independently of any direct antimicrobial effects [33–35]. In this study, the rate of CR achieved through H. pylori eradication alone in the HPN group was higher compared to those in previous studies [23, 26, 29]. The prevalence of H. pylori infection in the Honam Province is higher compared to those of other regions within South Korea [17]. In regions with a high prevalence of H. pylori infection, even when an HPN result is obtained, the possibility of past H. pylori infection, NHPH infection, or false negative results attributed to unreported use of acid suppressants or atrophic changes in the gastric mucosa should be considered. In such cases, CR could have probably been achieved through H. pylori eradication. Therefore, considering H. pylori eradication for the HPN group may be appropriate, especially in regions with a high prevalence of H. pylori infection. However, our results need to be interpreted with caution, and future studies incorporating systematic NHPH‑targeted molecular diagnostics and comprehensive microbiologic evaluation will be necessary to clarify the true contribution of NHPH to the pathogenesis of HPN gastric MALT lymphoma.
For patients who achieved CR but later relapsed, factors such as disease stage and LAP status at diagnosis appeared to have exhibited an influence. Patients with LAP or those diagnosed at advanced stages must undergo close monitoring, even after achieving CR. Previous studies report a median time to relapse of 11.5 months, with a maximum of 46 months after achieving CR [29]. Some studies report a mean time to relapse of 33.1 months and a maximum of 53.2 months [36]. A meta-analysis of four studies report a recurrence rate of 2.2% per year [7]. As revealed by the findings of our study, the potential for recurrence should be considered in patients diagnosed with advanced stage or LAP, and frequent follow-up visits may be necessary.
The strengths of this study include its large-scale, multicenter design, which enhances the generalizability of the findings. However, as a retrospective study, it has some limitations, such as variations in RT, chemotherapy regimens, and eradication protocols across various hospitals and physicians. These variations are inherent limitations of retrospective studies. In addition, although systemic lymphoma involving the stomach was carefully excluded through baseline clinical, radiologic, and, when indicated, bone marrow examination, the possibility of unrecognized systemic lymphoma cannot be completely ruled out. Furthermore, the API2–MALT1 chimeric gene status is an important prognostic and predictive marker in gastric MALTO lymphoma. In our study, we additionally attempted to assess this marker by the fluorescence in situ hybridization image in a subset of archival formalin-fixed paraffin-embedded tissue blocks, the overall staining quality was suboptimal because of block age and other technical factors, resulting in largely non-informative findings and precluding its cooperation into our prognostic analysis. Finally, even though patients with short follow-up were excluded, late responses might not have been fully identified, potentially leading to an underestimation of the true remission rate. Future studies is needed to address the gaps identified in this study.
Conclusions
Patients with gastric MALT lymphoma generally have a favorable prognosis, and H. pylori eradication can lead to CR, even in H. pylori-negative MALT lymphoma cases. Accurate staging at diagnosis is essential for optimal management, as disease stage and the presence of lymphadenopathy are key predictors of relapse.
Supplementary Information
Acknowledgements
Not applicable.
Abbreviations
- PGLs
Primary gastric lymphomas
- H. pylori
Helicobacter pylori
- MALT
Mucosa-associated lymphoid tissue
- HPP
Helicobacter pylori positive
- HPN
Helicobacter pylori negative
- LAP
Lymphadenopathy
- UBT
Urea breath test
- PCR
Polymerase chain reaction
- CR
Complete remission
- IQR
Interquartile range
- CI
Confidence interval
- aHR
Adjusted hazard ratio
- HR
Hazard ratio
- RT
Radiotherapy
- CIR
Cumulative incidence of relapse
Authors’ contributions
1 SYP and 2 SYS, study concept and design; analysis and interpretation of data; drafting and finalizing the manuscript; study supervision; 1 JWK and 2 DHY, conducting the study, collecting and interpreting data, and drafting the manuscript; 1 HSY, 1 GRY, 2 BCJ, 3 JIL, 3 YDK, 4 SCC and 5 WSL, collecting and interpreting data; 6 SSK, analysis and review of the pathological findings. All authors have read and approved this manuscript.
Funding
This study was supported by the Chonnam National University Hospital Research Institute of Clinical Medicine (BCRI25035) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF2021R1F1A1059503). This funding source had no role in the design of this study and collection, analysis and interpretation of data and in writing the manuscript.
Data availability
The datasets generated during and/or analyzed during the current study are available from corresponding author under reasonable request.
Declarations
Ethics approval and consent to participate
This study complies with the standards of the Declaration of Helsinki and current ethical guidelines. This study was approved by the Chonnam National University Hospital Institutional Review Board (IRB No.: CNUH-2023-304). Since this is a retrospective study, a written consent is waived by an IRB and is deemed unnecessary.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Jin Won Kim and Dong-Han Yeom contributed equally to this work as first author.
Contributor Information
Seon-Young Park, Email: drpsy@naver.com.
Seung-Young Seo, Email: bear7905@jbnu.ac.kr.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from corresponding author under reasonable request.