Prevention and management of secondary central nervous system lymphoma

Abstract

Secondary central nervous system (CNS) lymphoma (SCNSL) is defined by the involvement of the CNS, either at the time of initial diagnosis of systemic lymphoma, or in the setting of relapse, either isolated or with synchronous systemic disease. The risk of CNS involvement in patients with diffuse large B-cell lymphoma is approximately 5%, however, certain clinical and biological features have been associated with a risk of up to 15%. There has been growing interest in improving the definition of patients at increased risk of CNS relapse, as well as identifying effective prophylactic strategies to prevent it. SCNSL often occurs within months of initial lymphoma diagnosis, suggesting presence of occult disease at diagnosis in many cases. The differing presentations of SCNSL present a therapeutic challenge of control of both systemic disease and CNS disease, which uniquely requires agents that penetrate the blood brain barrier. Outcomes are generally poor with a median overall survival of approximately 6 months in retrospective series, particularly those presenting with SCNSL after prior therapy. Prospective studies of intensive chemotherapies containing high-dose methotrexate (HD-MTX), followed by haematopoietic stem cell transplantation have shown the most favourable outcomes, especially for patients receiving thiotepa-based conditioning regimens. However, a proportion of patients will not respond to induction therapies or subsequently relapse, indicating the need for more effective treatment strategies. In this review we focus on the identification of high-risk patients, prophylaxis strategies and recent treatment approaches for SCNSL. The incorporation of novel agents to immunochemotherapy deserves further study in prospective trials.

Treatment Strategies and Prognostic Factors in Secondary Central Nervous System Lymphoma: A Multicenter Study of 124 Patients

“…Recently, position articles on SCNSL management have been published. 18,21 Hence, we conducted this retrospective real-world study of prognostic factors and long-term outcome in 124 SCNSL patients intensively treated in curative intention at 5 hematologic departments.…”

Imaging of Lymphomas Involving the CNS: An Update-Review of the Full Spectrum of Disease with an Emphasis on the World Health Organization Classifications of CNS Tumors 2021 and Hematolymphoid Tumors 2022

“…48 Although historically, it has been thought that secondary lymphomas presented with leptomeningeal involvement in a high proportion of cases (around 70% 11 ); more recent data differ, suggesting parenchymal involvement in 40%-60%, leptomeningeal in 20%-30%, and both in 10% (Fig 8). 49,50 This higher proportion of parenchymal involvement in secondary lymphoma is important to consider in the radiologic interpretation because it is nonspecific for differentiation from primary CNS lymphoma, in which parenchymal lesions are almost constant. 11 Despite these differing disease distributions, imaging can frequently overlap, and differentiation between primary and secondary must rely on other staging examinations, such as a PET/CT scan, bone marrow aspiration, testicular sonography, vitreal examination, and the patient's history of systemic lymphoma.…”

“…11 Despite these differing disease distributions, imaging can frequently overlap, and differentiation between primary and secondary must rely on other staging examinations, such as a PET/CT scan, bone marrow aspiration, testicular sonography, vitreal examination, and the patient's history of systemic lymphoma. 48,50…”

CAR T-cell-associated neurotoxicity in central nervous system hematologic disease: Is it still a concern?

“…SCNSL is more likely to occur in a relapsed setting of a systemic NHL. Secondary CNS relapses are uncommon yet with devastating complications; incidence can reach up to 15% in high-risk patients ( 44 ). Elevated risk factors of CNS relapse in the validated 6-score risk model (CNS-IPI) include age >60, performance status >1, elevated LDH, extranodal sites >1, stage III or IV disease, and kidney or adrenal involvement ( 45 ).…”

“…Elevated risk factors of CNS relapse in the validated 6-score risk model (CNS-IPI) include age >60, performance status >1, elevated LDH, extranodal sites >1, stage III or IV disease, and kidney or adrenal involvement ( 45 ). Double-hit lymphoma is also associated with a higher risk of CNS relapse ( 44 ). CNS recurrence is typically leptomeningeal or confined to the brain parenchyma rather than the spinal cord ( Figure 2 ).…”