Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Feasibility of oral doxycycline as first-line therapy for conjunctival mucosa-associated lymphoid tissue lymphoma

A Correction to this article was published on 18 August 2023

This article has been updated

Abstract

Objectives

To investigate the long-term outcomes of oral doxycycline as first-line treatment in patients with conjunctival extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).

Methods

In this case series, the medical records of 67 patients with conjunctival MALT lymphoma who received doxycycline as their primary treatment and were followed up for at least 5 years were retrospectively reviewed. Progression-free survival (PFS) was analysed at 3, 5, and 10 years after the initial doxycycline treatment. A Cox proportional hazards model was used to assess the independent risk factors for progression.

Results

After the initial treatment, 25 patients (37.3%) achieved a complete response, 8 patients (11.9%) achieved a partial response, 30 patients (44.8%) showed stable disease, and 4 patients (6.0%) showed disease progression. The median PFS in all patients was 168 months, and the 3-, 5- and 10-year PFS rates for all patients were 70%, 65%, and 62%, respectively. No further progression was observed 6 years after the initial doxycycline treatment. Younger age and TNM stage T1c were significant risk factors for the time to progression in the multivariate Cox regression analysis (pā€‰<ā€‰0.05). Additional doxycycline (>2 cycles) showed no benefit. There were no serious adverse events associated with doxycycline therapy, and most patients were successfully salvaged by second-line treatments, including radiotherapy and chemotherapy.

Conclusion

In this case series, oral doxycycline treatment yielded acceptable long-term PFS with minimal complications. Especially in patients with stage T1a or T1b conjunctival MALT lymphoma, first-line doxycycline treatment could be considered under close monitoring for at least 6 years.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Overall treatment sequence according to the response of first-line doxycycline therapy.
Fig. 2: Survival analyses and proposed treatment algorithm using doxycycline as first-line therapy.

Similar content being viewed by others

Data availability

All data relevant to the study are included in the article or uploaded as supplementary information.

Change history

References

  1. Yen MT, Bilyk JR, Wladis EJ, Bradley EA, Mawn LA. Treatments for ocular adnexal lymphoma: a report by the american academy of ophthalmology. Ophthalmology. 2018;125:127ā€“36.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  2. Stefanovic A, Lossos IS. Extranodal marginal zone lymphoma of the ocular adnexa. Blood. 2009;114:501ā€“10.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

  3. McKelvie PA. Ocular adnexal lymphomas: a review. Adv Anat Pathol. 2010;17:251ā€“61.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  4. Kirkegaard MM, Coupland SE, Prause JU, Heegaard S. Malignant lymphoma of the conjunctiva. Surv Ophthalmol. 2015;60:444ā€“58.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  5. Tanenbaum RE, Galor A, Dubovy SR, Karp CL. Classification, diagnosis, and management of conjunctival lymphoma. Eye Vis (Lond). 2019;6:22.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  6. White WL, Ferry JA, Harris NL, Grove AS Jr. Ocular adnexal lymphoma. A clinicopathologic study with identification of lymphomas of mucosa-associated lymphoid tissue type. Ophthalmology. 1995;102:1994ā€“2006.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  7. Salar A. Gastric MALT lymphoma and Helicobacter pylori. Med Clin (Barc). 2019;152:65ā€“71.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  8. Melenotte C, Mezouar S, Mege JL, Gorvel JP, Kroemer G, Raoult D. Bacterial infection and non-Hodgkinā€™s lymphoma. Crit Rev Microbiol. 2020;46:270ā€“87.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  9. Ferreri AJ, Ponzoni M, Guidoboni M, Resti AG, Politi LS, Cortelazzo S, et al. Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial. J Natl Cancer Inst. 2006;98:1375ā€“82.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  10. Kim TM, Kim KH, Lee MJ, Jeon YK, Lee SH, Kim DW, et al. First-line therapy with doxycycline in ocular adnexal mucosa-associated lymphoid tissue lymphoma: a retrospective analysis of clinical predictors. Cancer Sci. 2010;101:1199ā€“203.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  11. Ferreri AJ, Govi S, Pasini E, Mappa S, Bertoni F, Zaja F, et al. Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial. J Clin Oncol. 2012;30:2988ā€“94.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  12. Han JJ, Kim TM, Jeon YK, Kim MK, Khwarg SI, Kim CW, et al. Long-term outcomes of first-line treatment with doxycycline in patients with previously untreated ocular adnexal marginal zone B cell lymphoma. Ann Hematol. 2015;94:575ā€“81.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  13. Collina F, De Chiara A, De Renzo A, De Rosa G, Botti G, Franco R. Chlamydia psittaci in ocular adnexa MALT lymphoma: a possible role in lymphomagenesis and a different geographical distribution. Infect Agent Cancer. 2012;7:8.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  14. Ferreri AJ, Guidoboni M, Ponzoni M, De Conciliis C, Dellā€™Oro S, Fleischhauer K, et al. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst. 2004;96:586ā€“94.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  15. Ponzoni M, Ferreri AJ, Guidoboni M, Lettini AA, Cangi MG, Pasini E, et al. Chlamydia infection and lymphomas: association beyond ocular adnexal lymphomas highlighted by multiple detection methods. Clin Cancer Res. 2008;14:5794ā€“5800.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  16. Yoo C, Ryu MH, Huh J, Park JH, Kang HJ, Ahn HS, et al. Chlamydia psittaci infection and clinicopathologic analysis of ocular adnexal lymphomas in Korea. Am J Hematol. 2007;82:821ā€“3.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  17. Daibata M, Nemoto Y, Togitani K, Fukushima A, Ueno H, Ouchi K, et al. Absence of Chlamydia psittaci in ocular adnexal lymphoma from Japanese patients. Br J Haematol. 2006;132:651ā€“2.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  18. Aigelsreiter A, Leitner E, Deutsch AJ, Kessler HH, Stelzl E, Beham-Schmid C, et al. Chlamydia psittaci in MALT lymphomas of ocular adnexals: the Austrian experience. Leuk Res. 2008;32:1292ā€“4.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  19. Zhang D, Dong L, Li H, Jin H, Ye H, Zhou X, et al. Ocular adnexal mucosa-associated lymphoid tissue lymphoma in Northern China: high frequency of numerical chromosomal changes and no evidence of an association with Chlamydia psittaci. Leuk Lymphoma. 2010;51:2031ā€“8.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  20. Jaffe ES, Harris NL, Stein H, Isaacson PG. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood. 2008;112:4384ā€“99.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

  21. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375ā€“90.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  CASĀ  Google ScholarĀ 

  22. Coupland SE, White VA, Rootman J, Damato B, Finger PT. A TNM-based clinical staging system of ocular adnexal lymphomas. Arch Pathol Lab Med. 2009;133:1262ā€“7.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  23. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non-Hodgkinā€™s lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17:1244.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  24. Kwon M, Lee JS, Lee C, Yoon DH, Sa HS. Prognostic factors for relapse and survival among patients with ocular adnexal lymphoma: validation of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM classification. Br J Ophthalmol. 2021;105:279ā€“84.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  25. Cho EY, Han JJ, Ree HJ, Ko YH, Kang YK, Ahn HS, et al. Clinicopathologic analysis of ocular adnexal lymphomas: extranodal marginal zone b-cell lymphoma constitutes the vast majority of ocular lymphomas among Koreans and affects younger patients. Am J Hematol. 2003;73:87ā€“96.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  26. Woo JM, Tang CK, Rho MS, Lee JH, Kwon HC, Ahn HB. The clinical characteristics and treatment results of ocular adnexal lymphoma. Korean J Ophthalmol. 2006;20:7ā€“12.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  27. Yoon JS, Ma KT, Kim SJ, Kook K, Lee SY. Prognosis for patients in a Korean population with ocular adnexal lymphoproliferative lesions. Ophthalmic Plast Reconstr Surg. 2007;23:94ā€“99.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  28. Nam SW, Woo KI, Kim YD. Characteristics of primary extranodal marginal zone B-cell lymphoma in Korea: conjunctiva versus other ocular adnexa. Br J Ophthalmol. 2018;102:502ā€“8.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Concept and design: TMK and HJC. Acquisition, analysis, or interpretation of data: SHC, MKY, MK and HJC. Manuscript draft: SHC and HJC. Critical revision of the manuscript for important intellectual content: SHC, MKY, MK and HJC. Statistical analysis: SHC; Administrative, technical, or material support: MKY and TMK; Supervision: TMK and HJC; Guarantor: HJC.

Corresponding author

Correspondence to Hyuk Jin Choi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisherā€™s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised: The sentence ā€œOlder age and TNM stage T1c were significant risk factors for the time to progression in the multivariate Cox regression analysis (p<0.05)ā€ in the abstract was corrected to read as follows: ā€œYounger age and TNM stage T1c were significant risk factors for the time to progression in the multivariate Cox regression analysis (p<0.05)ā€.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Choi, S.H., Yang, M.K., Kim, T.M. et al. Feasibility of oral doxycycline as first-line therapy for conjunctival mucosa-associated lymphoid tissue lymphoma. Eye 38, 82ā€“88 (2024). https://doi.org/10.1038/s41433-023-02635-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41433-023-02635-4

Search

Quick links