Infectious Disease Associations in Advanced Stage, Indolent Lymphoma (Follicular, FL and Non-Follicular, nFL): Developing a Lymphoma Prevention Strategy.

Background: The antigen-drive association of gastric MALT lymphoma with H. pylori is well recognized. Successful antibiotic therapy can result in lymphoma remission, and with it, lymphoma prevention. We have sought to prospectively identify possible associated infections in patients with non-bulky, advanced stage indolent lymphoma as the first step to such a lymphoma treatment/prevention strategy. These patients are often candidates for “watch and wait” and it is during this period that a window of opportunity may exist to identify and treat related infections.

Methods: Patients with a new diagnosis of indolent lymphoma (FL and nFL), stages II (intra-abdominal), III and IV fulfilling GELF criteria for observation were eligible. Studies performed: Stool H. pylori, Hepatitis C and Borrelia serologies, Borrelia and Chlamydia fixed tissue PCR, peripheral blood mononuclear cell PCR for Chlamydia, and a hydrogen breath test for small bowel bacterial overgrowth.

Results: 55 patients have been enrolled with IRB informed consent: 32 females, 23 males; median age, 54 years (21–77); 30 FL, 25 nFL; stage II (4 pt), III (22), and IV (29). All met GELF criteria for observation. Infections tested include: H. pylori (13 positive: 6 FL, 7 nFL); Hepatitis C (3+; 1 FL, 2 nFL); and small bowel bacterial overgrowth (10+; 4 FL, 6 nFL). Borrelia serologies and tissue PCR were negative in all 13 pts tested. Chlamydia psittaci tissue PCR positive in 1 FL (12 negative). Thus, 20 of 54 (37%) patients have had at least one positive study; and, to date we have observed lymphoma responses after successful antibiotic therapy alone in 6 of 20: H. pylori (1 FL with CRu for 20+ months; 1 nFL with transient near CR); Hepatitis C (1 FL with PR but HCV persistent; 2 nFL (1 CR for 24+ mos; 1 stable, currently on HCV therapy); SBBO (1 FL in PR for 28+ mos). Of interest, the patients with associated infections but without lymphoma response to antibiotics, appear to have required institution of lymphoma treatment sooner than those without initial associated infections (Treatment free survival 48% vs. 87.5%, p=0.08; 33 months median f/u from diagnosis), possibly suggesting a different biology.

Conclusion: Infections are common in advanced stage indolent lymphoma (37% in our series). Anecdotal lymphoma responses have been seen and 2 have been durable CRs (10%) ongoing for 20+ mos following infection eradication alone. The identification and treatment of associated infections may be a first step toward developing a lymphoma prevention strategy.