Chlamydophila Psittaci Eradication With Doxycycline As First-Line Targeted Therapy for Ocular Adnexae Lymphoma: Final Results of an International Phase II Trial

Abstract

<jats:sec><jats:title>Purpose</jats:title><jats:p>The pathogenic association between Chlamydophila psittaci (Cp) and ocular adnexal marginal zone lymphoma (OAMZL) and the efficacy of doxycycline monotherapy have been investigated in retrospective series with variations in stage, management, and follow-up duration. To our knowledge, this is the first international phase II trial aimed at clarifying Cp prevalence and activity of first-line doxycycline in a homogeneous series of consecutive patients with newly diagnosed stage I OAMZL.</jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p>Forty-seven patients were registered. Tumor tissue, conjunctival swabs, and peripheral blood from 44 patients were assessed for seven Chlamydiaceae infections by three polymerase chain reaction protocols. Thirty-four patients with measurable or parametrable disease were treated with doxycycline and assessed for chlamydial eradication and lymphoma response (primary end point).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Cp DNA was detected in biopsies of 39 patients (89%); no other Chlamydiaceae were detected. Twenty-nine patients had Cp DNA in baseline swabs and/or blood samples and were evaluable for chlamydial eradication, which was achieved in 14 patients (48%). Lymphoma regression was complete in six patients and partial in 16 (overall response rate, 65%; 95% CI, 49% to 81%); 11 had stable disease, and one had progressive disease. At a median follow-up of 37 months (range, 15 to 62 months), 20 patients remained relapse free (5-year progression-free survival [PFS] ± standard deviation, 55% ± 9%). Cp eradication was associated with improved response rate (86% v 47%; P = .02) and 5-year PFS (68% v 47%; P = .11).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Upfront doxycycline is a rational and active treatment for patients with stage I Cp-positive OAMZL. Lymphoma regression is consequent to Cp eradication, which can easily be monitored on conjunctival and blood samples. Prospective trials aimed at identifying more effective administration schedules for doxycycline are warranted.</jats:p></jats:sec>

Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study

“…8,9 Consequently, doxycycline treatment was studied as an initial therapeutic approach to POAML in several studies. [37][38][39] The overall response rate ranges from 45% to 65% in most studies 37,40 but was zero in a study reported by Grunberger et al 41 The 5-year For personal use only. on April 29, 2019.…”

“…38,42 Information on C psittaci infection was reported in only 3 of the 9 studies. [38][39][40] Kim et al 40 reported equal responses in patients with C psittaci-positive and negative POAML, while 2 trials from Italy showed better responses in C psittaci-positive patients. 38,39 Only 1 of our patients received treatment with doxycycline with no response.…”

Diagnostic Workup of Small B Cell Lymphomas: A Laboratory Perspective

“…The role of Helicobacter pylori (HP) has been studied in detail in these tumors and consequently antibiotic therapy is now the cornerstone of treatment. Microbial agents have been also implicated in other types of ENMZL: chlamydia psittaci in ocular adnexa, borrelia burgdorferi in skin, and campylobacter jejuni in small intestinal ENMZL [21][22][23]. ENMZL is also associated with long-standing autoimmune disorders involving the thyroid and salivary glands.…”

Emerging Role of Infectious Etiologies in the Pathogenesis of Marginal Zone B-cell Lymphomas

“…Of note, MZL regression after doxycycline treatment has also been observed in some lymphomas with no C. psittaci presence as well as in cases in which this treatment failed to eradicate the C. psittaci infection (76,80,81). This finding suggests that other doxycycline-sensitive microorganisms may be linked with the lymphoma.…”

“…A great deal of evidence supports a pathogenic association between C. psittaci and the development of MALT lymphoma of the ocular adnexa, ranging from the identification of chlamydial antigens in tumor tissue by immunohistochemistry and the detection of bacterial DNA in the tumor biopsies, to the visualization of the bacteria within tumor-infiltrating macrophages by electronic microscopy and their isolation from conjunctival swabs and the peripheral blood of patients (76,77). Moreover, development of metachronous C. psittaci-related lymphomas was described in the same patient after prolonged exposure to an infected animal (78).…”