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Comment & Response
June 2015

The Orbit and the Brain—Reply

Author Affiliations
  • 1Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark
  • 2Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark
  • 3Department of Ophthalmology, Glostrup University Hospital, Glostrup, Denmark
JAMA Ophthalmol. 2015;133(6):727-728. doi:10.1001/jamaophthalmol.2015.0367

In Reply We read with interest Ferreri’s comments on our multicenter work on OA-DLBCL.1 We are pleased to have the opportunity to contribute with further information regarding this uncommon subcategory of extranodal non-Hodgkin lymphoma.

Current information concerning clinical and histopathological characteristics of OA-DLBCL is sparse because investigations often are limited to series of ocular adnexal lymphomas covering a wider range of subtypes.2 Our retrospective international study included 100 patients with OA-DLBCL from 6 eye cancer centers during a 30-year period.1 The nature of this design left us with a relatively large cohort as compared with others, but at the same time we adopted the difficulties of selection bias inherent to our heterogeneous study population.1 Another important bias was related to the fact that staging procedures (eg, Ann Arbor staging) were far more exhaustive in the latter half of the study period.

Further, even in the postrituximab era of our study period, the applied treatment regimens varied across the participating centers and in many instances patients were not treated according to standard therapeutic guidelines for DLBCL,2,3 ie, rituximab–cyclophosphamide, hydroxydaunorubicin, vincristine sulfate, prednisone (R-CHOP) or R-CHOP–like therapy with or without consolidation radiation therapy. As addressed by Ferreri and others,2,4,5 recent experiences suggest that high-dose methotrexate–based CNS prophylaxis might reduce CNS relapse rates in high-risk patients with DLBCL, which may include a subgroup of patients with OA-DLBCL, although confirmative controlled trials are still lacking in this area.

In our study, details on CNS involvement or prophylaxis were reported only sporadically and incorporated in the Ann Arbor classification accordingly, as described in the following cases. One patient with concurrent OA-DLBCL and systemic DLBCL had CNS involvement (Ann Arbor stage IVE) at inclusion. This patient was treated with alkylating chemotherapy and consolidation radiation therapy, whereas no specific CNS-directed therapy was reported. Two of the included patients with concurrent OA-DLBCL and systemic DLBCL (Ann Arbor stage IIE and IVE disease) experienced a CNS relapse. Initially they were treated with cyclophosphamide, vincristine, prednisone therapy and CHOP plus consolidation radiation therapy, and at relapse with cyclophosphamide (1982) and palliation therapy with prednisone (1998).

Information on CNS prophylaxis, ie, intravenous high-dose methotrexate or intrathecal methotrexate, was recorded in 3 patients treated with R-CHOP or R-CHOP–like therapy. One had primary OA-DLBCL (Ann Arbor stage IE) and 2 had concurrent OA-DLBCL and systemic DLBCL (Ann Arbor stage IVE). Of these 3 patients, 2 were treated with intrathecal methotrexate and 1 was treated with unspecified methotrexate plus cytarabine. The patient with primary OA-DLBCL had complete remission, whereas the 2 others had died at follow-up (after 2004). Three patients with Ann Arbor stage IVE OA-DLBCL from the postrituximab era (after 2002) received cytarabine in addition to R-CHOP or R-CHOP–like therapy.

The difficult interpretations of therapy and survival outcomes in our cohort1 emphasize the importance of achieving consensus gathered in international guidelines of uncommon subtypes of extranodal DLBCL as well as attempting to pinpoint predictive risk factors, which may eventually identify putative, high-risk candidates with OA-DLBCL for CNS prophylaxis.

In conclusion, we extracted information on direct CNS involvement at diagnosis or relapse in 3 patients and the use of CNS prophylaxis in 6 patients from a total of 100 cases with OA-DLBCL. Thus, from our retrospective material we cannot show a higher tendency of CNS dissemination from OA-DLBCL as compared with other types of extranodal DLBCL.

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Article Information

Corresponding Author: Steffen Heegaard, MD, DMSc, Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Frederik V’s Vej 11, First Floor, DK-2100 Copenhagen, Denmark (sthe@sund.ku.dk).

Published Online: March 19, 2015. doi:10.1001/jamaophthalmol.2015.0367.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

References
1.
Munch-Petersen  HD, Rasmussen  PK, Coupland  SE,  et al.  Ocular adnexal diffuse large B-cell lymphoma: a multicenter international study [published online November 13, 2014].  JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2014.4644.Google Scholar
2.
Ponzoni  M, Govi  S, Licata  G,  et al.  A reappraisal of the diagnostic and therapeutic management of uncommon histologies of primary ocular adnexal lymphoma.  Oncologist. 2013;18(7):876-884.PubMedGoogle ScholarCrossref
3.
Feugier  P, Van Hoof  A, Sebban  C,  et al.  Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte.  J Clin Oncol. 2005;23(18):4117-4126.PubMedGoogle ScholarCrossref
4.
Ferreri  AJM, Bruno-Ventre  M, Donadoni  G,  et al.  Risk-tailored CNS prophylaxis in a mono-institutional series of 200 patients with diffuse large B-cell lymphoma treated in the rituximab era [published online October 14, 2014].  Br J Haematol. doi:10.1111/bjh.13194.Google Scholar
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Ghose  A, Kundu  R, Latif  T.  Prophylactic CNS directed therapy in systemic diffuse large B cell lymphoma.  Crit Rev Oncol Hematol. 2014;91(3):292-303.PubMedGoogle ScholarCrossref
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