Gastric mucosa-associated lymphoid tissue lymphoma detected by clonotypic polymerase chain reaction despite continuous pathologic remission induced by involved-field radiotherapy

Purpose Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is indolent and often associated with Helicobacter pylori bacterial infection. H pylori-independent MALT develops either in the absence of the bacteria or persists after bacterial eradication. We have previously demonstrated long-term pathologic remission after involved-field radiotherapy therapy (IFRT). We determined molecular remission status by clonotypic polymerase chain reaction (PCR). Patients and Methods Twenty-four consecutive patients with stage I to IIE gastric MALT lymphoma who obtained a pathologic remission after IFRT alone were evaluated. All had at least two follow-up endoscopic gastroduodenal biopsies at Memorial Sloan-Kettering Cancer Center. IFRT median dose was 30 Gy (range, 28.5 to 43.5 Gy). Post-treatment biopsies were subjected to semi-nested clonotypic PCR. Results All patients obtained a complete response based on routine immunohistochemical pathologic analysis of random post-treatment gastric biopsies. Median follow-up from completion of IFRT was 63 months (range, 19 to 117 months). Event-free survival was 96%; 23 of 34 patients remained in clinical and pathologic complete remission. Baseline DNA extraction yielded 17 clone-specific primer pairs. At the first follow-up test, 14 of 17 pairs were PCR positive, Eight remained persistently positive; and one was persistently negative. Others were intermittently positive. Conclusion. Despite sustained biopsy-proven remissions for as long as 117 months after radiation, the vast majority of patients remain positive by clonotypic PCB. This suggests that the malignant clone is present but missing either an internal or external signal essential to the cancer phenotype. One possibility is that radiation eradicates the polyclonal H pylori-specific T cells eliminating critical local factors necessary for proliferation of the monoclonal B cells.