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Annals of Oncology Advance Access originally published online on March 15, 2007
Annals of Oncology 2007 18(6):1085-1089; doi:10.1093/annonc/mdm073
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© 2007 European Society for Medical Oncology

hematologic malignancies

Central nervous system occurrence in elderly patients with aggressive lymphoma and a long-term follow-up

M Björkholm1,*, H Hagberg2, H Holte3, S Kvaloy3, L Teerenhovi4,{dagger}, H Anderson5, E Cavallin-Ståhl6, J Myhre7, H Pertovaara8, Å Öst9,10, B Nilsson11 and E Ösby1

1 Department of Medicine, Karolinska University Hospital, Stockholm
2 Department of Oncology, Uppsala Academic Hospital, Uppsala, Sweden
3 Rikshospitalet-Radiumhospitalet, Medical Center, Oslo, Norway
4 Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
5 Department of Cancer Epidemiology, Lund University, Lund
6 Department of Oncology, University Hospital, Lund, Sweden
7 Department of Hematology, the Finsen Center, Rigshospitalet, Copenhagen, Denmark
8 Department of Oncology, Tampere University Hospital, Tampere, Finland
9 Department of Clinical Pathology, Medilab, Täby
10 Karolinska Institutet, Stockholm
11 Unit of Cancer Epidemiology, Karolinska University Hospital and Institutet, Stockholm, Sweden

* Correspondence to: Dr M. Björkholm, Department of Medicine, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Tel: +46-8-51774198; Fax: +46-8-318264; E-mail: magnus.bjorkholm{at}karolinska.se

Background: Secondary central nervous system (CNS) involvement by aggressive lymphoma is a well-known and dreadful clinical complication. The incidence and risk factors for CNS manifestation were studied in a large cohort of elderly (>60 years) patients with aggressive lymphoma.

Patients and methods: In all, 444 previously untreated patients were randomized to receive 3-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (doxorubicin substituted by mitoxantrone) chemotherapy with or without filgrastim. Prophylactic intrathecal methotrexate was given to patients with lymphoma involvement of bone marrow, testis and CNS near sites.

Results: In all 29 of 444 (6.5%) developed CNS disease after a median observation time of 115 months. CNS was the only site of progression/relapse in 13 patients while part of a systemic disease manifestation in 16 patients. In univariate risk factor analysis, CNS occurrence was associated with extranodal involvement of testis (P = 0.002), advanced clinical stage (P = 0.005) and increased age-adjusted International Prognostic Index score (aaIPI; P = 0.035). In multivariate analysis, initial involvement of testis remained significant and clinical stage was of borderline significance. The median survival time was 2 months after presentation of CNS disease.

Conclusion: A significant proportion of elderly patients with advanced aggressive lymphoma will develop CNS disease. CNS occurrence is related to testis involvement, advanced clinical stage and high aaIPI and the prognosis is dismal.

Key words: aggressive non-Hodgkin's lymphoma, central nervous system, CHOP, CNOP, elderly, G-CSF

{dagger} Deceased.

Received for publication November 10, 2006. Revision received January 30, 2007. Accepted for publication February 1, 2007.


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