Chlamydia Psittaci-Eradicating Antibiotic Therapy as a Potential Therapeutic Strategy Against Marginal Zone B-Cell Lymphoma of the Ocular Adnexa.
Authors: Ferreri Andres J. , Ponzoni Maurilio , Guidoboni Massimo , Lettini Antonia A. , Caggiari Laura , De Conciliis Carlo , Resti Antonio Giordano , Mazzi Benedetta , Stefano Rosalba , Boiocchi Mauro , Doglioni Claudio , Villa Eugenio , Dolcetti Riccardo 
Published: October 2019

Abstract
Background: Chlamydia psittaci (Ch.ps.) DNA has been detected in tumor tissue of 80% of patients with ocular adnexal lymphoma (OAL) and in peripheral blood mononuclear cells (PBMCs) of 40% of them [Ferreri AJM, et al. J Natl Cancer Inst 96:586, 2004]. Chronic antigenic stimulation provided by Ch.ps. persistent infection may favor the development and sustaining of OAL. Removal of this stimulation with antibiotic therapy could result in lymphoma regression.
Aim: To assess the rate of Ch.ps. eradication and anti-lymphoma activity of antibiotic therapy in OAL patients.
Methods: Twelve patients with Ch.ps.-positive marginal zone B-cell lymphoma of the ocular adnexa, at diagnosis (n=5) or relapse, were treated with doxycycline 100 mg, bid orally, for three weeks. The presence of Ch.ps. DNA in lymphoma samples was assessed by multiplex touchdown PCR. Specificity of the amplified PCR fragments was confirmed by direct sequencing of both sense and anti-sense strands. The presence of Ch.ps. DNA in PBMCs collected before and one and 12 months after antibiotic therapy was evaluated in 11 cases. Six of these patients had Ch.ps.-positive PBMCs and were assessable for bacterial eradication rate. Nine patients had measurable disease at the time of therapy and were evaluable for objective response; a lymphomatous lesion of ocular adnexa was detected in all 9 evaluable patients: unilateral in three, bilateral in three, associated with regional lymphadenopathies in two, and with multiple subcutaneous nodules in one. Objective response was assessed one, three and six months after therapy conclusion and every six months during follow-up. Observation period after doxycycline ranged from 1 to 29 months (median 25).
Results: All patients but one completed antibiotic therapy, with excellent tolerability. At one month from doxycycline assumption, Ch.ps. DNA was no longer detectable in PBMC of the six positive patients; these results were confirmed at one year of fw-up in all the three assessable cases. Objective response was complete in two patients (26+ and 9+ months), partial in two (29+ and 6+ m.) and lower than 50% in two (3+ and 5+ m.), whereas one patient had stable disease at one month of fw-up. Two patients experienced progression and received salvage treatment. Importantly, two patients showed lymphoma regression in previously irradiated orbit, and the two patients with regional lymphadenopathies achieved complete response; doxycycline was the 4th-line treatment in one of them. Time to the best response ranged from 3 to 24 months. All patients are alive and well (median fw-up: 54 m.).
Conclusions: Ch.ps.-eradicating antibiotic therapy is followed by tumor regression in OAL patients, even after multiple relapses. Estimation of response rate requires a longer follow-up. A large phase II trial is warranted to confirm whether this fast, cheap and well-tolerated therapy may be a valid alternative to conventional, more aggressive strategies against OAL.