**3. Gastric MALT lymphoma is cured by first-line antibiotics eradicating**  *Hp* **infection**

Zullo et al. reviewed 1408 patients with gastric MALT lymphoma from 32 studies including 23 prospective and nine retrospective studies, to explore the treatment efficacies of first-line HPE and predictive markers of *Hp*-dependence [15]. In their studies, the determination of CR was mainly based on the tumors that regressed to achieve less than grade 2 (chronic active gastritis with florid lymphoid follicle formation) of Wotherspoon's scoring system [11]. Zullo et al. reported that tumors limited to the mucosa or submucosa were significantly closely associated with a higher CR rate (mucosa/submucosa vs. muscularis propria involvement and beyond: 82.2% vs. 54.5%; P = 0.0001) [15]. In addition, patients with tumors located at the distal lesions of the stomach (antrum and/or angulus) had a higher CR rate than those with tumors located at proximal lesions (gastric body and/ or fundus) (91.8% vs. 75.7%; P = 0.0037) [15]. In a long-term follow-up of 994 patients, 72 patients (7.24%) experienced relapse of MALT lymphoma; among these, 12 patients had *Hp* infections [15].

In a retrospective multicenter study from Japan, Nakamura et al. showed that among 420 patients with successful HPE, 284 (67.6%) patients achieved pathological CR (pCR, absence of CLLs and without aggregation of small lymphocytes), and 39 (9%) patients had probable minimal residual disease (pMRD; presence of atypical lymphoid aggregates or nodules in at least two following assessments) according the Groupe d'Etude des Lymphomes de l'Adult (GELA) criteria, with an overall CR rate of 77% (323 patients) [47]. The histological scoring system proposed by GELA is currently recommended to assess whether tumors of gastric MALT lymphoma can achieve CR in a series of examinations after HPE using combined endoscopic findings and histological manifestations, in which CR was defined as the total vanishing of the gross tumor and a negative histological finding (pCR or pMRD) [48, 49]. Nakamura also showed that the median time to CR for these *Hp*-dependent tumors was four months (range from 1 to 94 months), and proximal or multiple locations, and non-superficial manifestations (such as hyperemia patches) were significantly associated with *Hp*-independence [47]. Tsai et al. and Kuo et al. also showed that ulcerative lesions, proximal locations of tumors, and tumors invading the muscularis propria or serosa correlated significantly with the *Hp*-independence of gastric MALT lymphoma [25, 39]. In another large cohort study of a Korean population, Gong et al. reported that *Hp* infection was detected in 317 (91.9%) of 345 patients with gastric MALT lymphoma using histology, a urea breath test, a rapid urease test, or a serologic test [50]. Gong showed that among *Hp*-positive patients, HPE resulted in a CR rate of 84.5% (n = 268), with a median time of 9.8 months (range 7.1 to 15.6 months) to CR, whereas 29 patients (10.7%) with CR developed relapses of MALT lymphoma [50].

Regarding the duration for achieving CR of tumors after completion of HPE, most studies showed that intervals are varied, ranging from quick (one to six months) to moderate (more than six months to 12 months) [15, 16, 39, 47, 51, 52]. In a prospective study, Hong et al. revealed that 85 (94.4%) of 90 patients with gastric MALT lymphoma achieved CR after HPE, with a median time to CR of three months (range, 1 to 24 months); 79 (92.9%) patients achieved CR at six months,

*Revisiting the Full Spectrum of* Helicobacter pylori*-Related Gastric Lymphoma DOI: http://dx.doi.org/10.5772/intechopen.97424*

and another six (7.1%) patients achieved CR at 12 months [53]. Zullo et al. also showed that the median interval to CR was five months for patients with gastric MALT lymphoma after treating HPE, whereas few patients needed at least two years to achieve CR [15]. Fischbach et al. analyzed 108 gastric MALT lymphoma patients who underwent gross normalization but had histologically minimal residuals at 12 months after HPE, and found that 35 patients (32.4%) achieved subsequent CR after more than 24 months of follow-up post-HPE [54]. Terai et al. reported that among 74 patients with gastric MALT lymphoma, 56 (75.7%) patients had CR and 12 had gross tumor regression with histological residual tumor (hRD) at 12 months after successful HPE, while 11 patients with hRD achieved CR (ranging from 14 to 40 months after HPE) at a subsequent follow-up [55]. Tsai et al. further showed among patients with *Hp*-positive gastric MALT lymphoma who entered into a prospective study of the Taiwan Cooperative Oncology Group (TCOG) 3206 trial, the median time to CR was 4.0 months (range, 1 to 16 months) after HPE; among these patients, six (23%) patients achieved CR within 6 to 12 months, and four (15.4%) patients required 12 to 24 months to attain CR [25]. These results suggest that longer observation and refraining from the immediate administration of second-line therapy (including chemotherapy or radiotherapy) are recommended for gastric MALT lymphoma patients who had improved symptoms, partial remission (PR), or stable status of tumors even at 12 months or longer after HPE. In other words, a "watch and wait" treatment strategy may be advisable for patients with gastric MALT lymphoma who achieved probable minimal residual disease or tumor PR (according to GELA criteria) after successful HPE.
