SAN FRANCISCO—Investigators have validated the German High-Grade Non-Hodgkin Lymphoma Study Group’s new prognostic model that incorporates 5 International Prognostic Index (IPI) factors—age older than 60 years, LDH greater than N, stage 3 or 4, and more than 1 extranodal site—in addition to kidney/adrenal gland involvement to predict risk of secondary central nervous system (CNS) disease in patients with aggressive B-cell lymphoma in an independent dataset, according to a presentation (Abstract 394) during the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.

“The model identifies a high-risk group in which diagnostic procedures to rule out CNS disease are highly recommended at diagnosis, including MRI of the head and cerebrospinal fluid analysis by cytology and flow cytometry and consideration of CNS-directed therapies,” said Kerry J. Savage, MD, MSc, Division of Medical Oncology, British Columbia Cancer Agency Centre for Lymphoid Cancer and the University of British Columbia in Vancouver, BC, Canada.

“Kidney/adrenal involvement is consistently associated with a high risk of CNS relapse in the rituximab treatment era, for which CNS prophylaxis should be incorporated into front-line therapy,” she added.

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For those at low (≤1%) or intermediate (approximately 5%) risk of CNS disease at 2 years, no diagnostic procedures and no prophylaxis are recommended.

Central nervous system relapse continues to pose a significant management challenge, despite improved outcomes in patients with aggressive B cell lymphomas, Dr. Savage explained. The study group’s model stratified 2,164 patients into 3 risk groups, low risk, defined as 0 to 1 factors and a 2-year CNS relapse risk of 0.6% (95% confidence interval [CI] 0.0-1.2); intermediate risk, 2 to 3 factors, 2-year CNS relapse risk of 3.4% (95% CI 2.2-4.6); and high risk, 4 to 6 factors, 2-year CNS relapse risk of 10.2% (95% CI 6.3-14.1).

The investigators validated this model in an independent cohort of 1,597 patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP chemotherapy at the British Columbia Cancer Agency (BCCA). Median follow-up for living patients was 4.2 years.

In this population, patients were more likely to have poor risk features, including PS greater than 1, advanced age, and a high IPI score.

“Applying the 6-factor model, very similar risk groups were identified,” she said. Low risk was 0.8% (95% CI 0.0-1.6%); intermediate risk, 3.9% (95% CI 2.3-5.5%); and high risk, 12% (95% CI 7.9-16.1%).

Median time to CNS relapse from time of diagnosis was 6.7 months in the BCCA group and 7.2 months in the German group, “highlighting that this event typically occurs early in the disease course,” Dr. Savage said.

In both datasets, kidney/adrenal involvement was highly associated with CNS relapse; 2-year CNS risk was 33% in the BCCA group and 14% in the German group, with the difference likely reflecting the higher risk patients in the BCCA population-based setting.

“The 3 group CNS risk model incorporating the 5 IPI factors and kidney-adrenal involvement is robust and reproducible for predicting the risk of CNS relapse,” Dr. Savage concluded.


  1. Savage, Kerry J., MD, MSc, et al. “394 Validation of a Prognostic Model to Assess the Risk of CNS Disease in Patients with Aggressive B-Cell Lymphoma.” ASH 2014. Oral Presentation. December 8, 2014.