Antibiotic Therapy of H. Pylori Negative Gastric MALT Lymphoma
Authors: Lee Seung Tae , Teegavarupu Purnima , Karri Anusha , Anireddy Saswatha , Hagemeister Fredrick B. , Romaguera Jorge E. , Fayad Luis , Rodriguez Maria A. , Samaniego Felipe , Fowler Nathan , Oki Yasuhiro , Turturro Francesco , Westin Jason R. , Kwak Larry W , Dabaja Bouthaina S. , Feng Lei , Davis R Eric , Neelapu Sattva S 
Published: October 2019

Abstract
Introduction
The causal association between H. pylori and gastric MALT lymphoma has been well demonstrated and H. pylori eradication with antibiotics has emerged as the standard therapy for Stage I H. pylori positive (HPP) gastric MALT lymphoma. As per the NCCN Guidelines, radiation therapy is the preferred treatment option for early stage H. pylori negative (HPN) gastric MALT lymphoma and antibiotic therapy is not indicated. However, successful treatment of HPN early stage gastric MALT lymphoma with antibiotics was reported in small series of patients by Raderer et al, Gut, 2006 [(5/6 patients achieved complete remission (CR)] and Asano et al, Tohoku J Exp Med, 2012 (5/17 patients achieved CR). Here, we report the outcome of Stage I HPP and HPN gastric MALT lymphoma patients treated with antibiotics at MD Anderson Cancer Center, Houston, Texas, USA over a period of 20 years.
Methods
We reviewed medical records of all pathologically proven gastric MALT lymphoma patients (n=128) referred to MD Anderson Cancer Center at initial diagnosis between 1991 and 2011. Only patients with Stage IAE disease were considered for this analysis. Patients with large cell transformation were excluded. H. pylori status was determined by histopathology and serum antibody assay. Clinical staging was determined by upper GI endoscopy with biopsy, bone marrow biopsy, and CT scans of neck, chest, abdomen, and pelvis and/or PET-CT scan. Response was assessed by upper GI endoscopy every 3-6 months until complete resolution of lymphoma. Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsies.
Results
Of the 128 patients reviewed, 81 patients had Stage IAE disease without histologic evidence of large cell transformation. The 81 Stage IAE patients were assigned to HPP (39/81, 48%) or HPN group (42/81, 52%) based on histopathologic evidence of H. pylori. The higher-than-expected proportion of HPN patients might be due to referral bias to a tertiary care cancer center. The results of H. pylori antibody serology are shown in Table 1. There was no significant difference in age, gender, and race between HPP and HPN groups. First-line antibiotic therapy was administered for all 39 (100%) HPP patients and 28/42 (67%) HPN patients. The CR rate after antibiotic therapy was significantly higher in HPP compared with HPN patients (22/39, 56% vs 7/28, 25%; p=0.019). The median time to achieve a CR was similar for the two groups (HPP: 7.8 mo, range 3-40 mo; HPN: 9.7 mo, range 3-35 mo; p=0.385). After a median follow-up of 110 mo for the HPP group and 91.5 mo for the HPN group, 3/22 (14%) and 2/7 (28%) responders relapsed, respectively (p=0.362). Patients who failed to achieve a CR with antibiotic therapy were mostly treated with radiation: 14/17 in the HPP group and 19/21 in the HPN group. All patients that received radiation achieved a CR. Of the patients in both groups who received upfront antibiotic therapy, there were no differences in time to progression (HPP, 90% vs HPN, 92% at 8 years; p=0.543) and overall survival (HPP, 93% vs HPN, 100% at 8 years; p=0.068).
Conclusions
Our results demonstrate that a substantial proportion of patients with Stage IAE HPN gastric MALT lymphoma achieve durable remission with antibiotic therapy alone. It is possible that such responses may be because of false-negative H. pylori test results or due to association of HPN gastric MALT lymphoma with other unidentified bacteria. We also observed that HPN gastric MALT lymphoma patients failing antibiotic therapy could be effectively salvaged with radiation therapy and their long-term outcome is not affected by delay from initial trial of antibiotic therapy. Thus, the results of this largest series-to-date of HPN patients treated with first-line antibiotic therapy, combined with results of smaller series reported previously, suggest that 1) antibiotic therapy should be considered as first-line therapy for Stage IAE HPN gastric MALT lymphoma patients, and 2) radiation therapy could be avoided in a subset of these patients.
Table 1. H. pylori status in Stage IAE gastric MALT lymphoma as determined by histopathology and H. pylori antibody. H. pylori positive by histology (n=39) H. pylori negative by histology (n=28) CR (n=22) Non-CR(n=17) CR (n=7) Non-CR(n=21) H. pylori Ab Positive 4 4 0 3 H. pylori Ab Negative 8 2 1 7 Not available 10 11 6 11
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.