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Blood, 23 April 2009, Vol. 113, No. 17, pp. 3896-3902.
Prepublished online as a Blood First Edition Paper on January 14, 2009; DOI 10.1182/blood-2008-10-182253.
 Previous Article | Next Article 
Submitted October 2, 2008
Accepted December 23, 2008
CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: An analysis of patients treated in the RICOVER-60 trial of the German high-grade non-Hodgkin lymphoma study group (DSHNHL)
Volkmar Boehme, Norbert Schmitz*, Samira Zeynalova, Markus Loeffler, and Michael Pfreundschuh
Department of Hematology and Stem Cell Transplantation, Asklepios Hospital St. Georg, Hamburg, Germany
Institute of Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
Department of Internal Medicine I, Saarland University, Homburg/Saar, Germany
* Corresponding author; email: n.schmitz{at}asklepios.com.
One thousand, two hundred and twenty-two patients treated in the RICOVER-60 trial were examined for CNS disease developing during first-line therapy or after a complete or partial remission had been achieved. Patients received six or eight courses of CHOP administered every 2 weeks (CHOP-14) with or without rituximab (R). CNS prophylaxis for patients with involvement of bone marrow, testes, upper neck, or head consisted of intrathecal (i.th.) methotrexate (day 1 and 5 of first 2 courses). Fifty-eight cases of lymphoma in the CNS were observed (36/609 patients in the CHOP-14 and 22/608 patients in the R-CHOP-14 arm). The estimated two-year incidence of CNS disease was 6.9% (CI 4.5; 9.3) after CHOP-14 and 4.1% (CI 2.3; 5.9) after R-CHOP-14. R-CHOP reduced the relative risk for CNS disease to 0.58 (95% CI 0.3;1.0, p=0.046). Cox regression analysis identified 'involvement of more than 1 extranodal site' and 'B-symptoms' as significant risk factors for CNS disease. Patients treated with R-CHOP-14 did not show any benefit from i.th. methotrexate. We conclude that elderly patients with aggressive CD20-positive lymphoma show a significantly lower incidence of CNS disease if treated with R-CHOP-14 instead of CHOP-14. I.th. methotrexate has no role in preventing CNS disease for patients treated with combined immunochemotherapy (R-CHOP-14) - with the possible exception of patients with testicular involvement. The original clinical trials are registered on www.clinicaltrials.gov as NCT000052936.
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