Secondary Central Nervous System Involvement with Concurrent Diffuse Large B Cell Lymphoma at Initial Presentation or at Relapse Is Associated with Zero Survival- a Decade's Experience from a Single Centre in Riyadh, Saudi Arabia

Background: Secondary central nervous system (CNS) involvement with diffuse large B cell lymphoma (DLBCL) is associated with poor outcomes. We looked at characteristics and outcomes of these patients treated at King Fahad Medical City, Riyadh over eleven year period from 2005-2016.

Methods: Out of 1235 patients diagnosed with lymphoma at our centre over a ten year period from 2005 to 2016 we identified 10 adult patients over the age of 18 years, who had DLBCL with secondary CNS involvement. It was a retrospective chart review.

Results: Out of 10 patients, 4 (40%) were males and 6 (60%) were females.7 of 10 (70%) were over 45 years of age. All patients had stage III disease or beyond with at least one extranodal involvement at presentation. All patients had evidence of CNS involvement either radiologically or histologically or both. 9 of 10 patients (90%) had CNS involvement within one year of presentation (whilst on treatment or within a year of diagnosis) while one patient had been treated for gastric lymphoma 10 years before relapse. 2 of 10 (20%) patients presented with concurrent CNS involvement at initial presentation while 8 of 10 (80%) had CNS involvement in addition to systemic disease due to progression of disease whilst on treatment or due to relapse. 3 of 10 (30%) patients who did not have CNS involvement at presentation received CNS prophylaxis (one patient received high dose methotrexate, the three other received intrathecal chemotherapy).7 of 10 (70%) patients received anthracycline containing chemotherapy with Rituximab as upfront, the other three were unfit for intensive chemotherapy. Treatment at relapse or on progression included various modalities including High Dose Methotrexate, High Dose Cytarabine or both, Whole Brain Radiotherapy, Intrathecal Chemotherapy, Temozolamide, however all patients received Rituximab. Only one patient underwent autologous stem cell transplant but relapsed shortly afterwards. After CNS involvement, all patients (n=7) were uniformly refractory to chemotherapy/radiotherapy or both. 3 patients were unfit to receive any treatment and died within a month of diagnosis. Median survival was only 3.5 months from the time of CNS involvement (range: 1-8 months). None of the patients were alive beyond 8 months of CNS involvement.

Discussion: To our knowledge this is the first case series of DLBCL with secondary CNS involvement from Middle East. This study shows that CNS involvement is rare but associated with extremely poor outcome as shown in other studies, with a median survival of only 3.5 months. None of the patients were responsive to therapy or were alive beyond 8 months of CNS involvement. It is interesting to note even 3 patients who had received some form of CNS prophylaxis also had CNS involvement, suggesting aggressive nature of disease and ineffective current form of CNS prophylaxis, even if given. Further studies are needed to define incidence and characteristics and outcomes of these patients from this region. Though numbers are small to make any specific recommendation, patients with high risk disease should be considered for intensive CNS prophylaxis upfront otherwise CNS involvement later would invariably associated with dismal outcome irrespective of any therapy. There is certainly urgent need for improvement in how we manage these high risk patients with probable inclusion of novel B cell antagonists and aggressive CNS prophylaxis upfront through well designed clinical trials.