Central Nervous System Prophylaxis in Aggressive B-cell Lymphoma
Research type
Research Study
Full title
Assessing the effectiveness of CNS prophylaxis strategies in patients with diffuse large B-cell lymphoma and CNS-IPI ≥4 and high-grade B cell lymphoma: a multi-center, retrospective analysis
IRAS ID
293804
Contact name
Mark Bishton
Contact email
Sponsor organisation
North Metropolitan Health Service
Duration of Study in the UK
0 years, 11 months, 28 days
Research summary
Research Summary\nSecondary Central Nervous System Lymphoma (SCNSL) is an uncommon but devastating complication of lymphoma, with poor outcomes. Identifying patients at greatest risk is imperative to direct prophylactic intervention.The most widely adopted prognostic model to identify patients at highest risk of CNS progression is the CNS-International prognostic Index (IPI) score.The score incorporates the clinical factors from the established IPI (LDH, age, stage, extra-nodal sites, performance status), with an additional point added for the presence of kidney or adrenal lymphoma involvement. Low, intermediate and high risk groups have 2 year CNS relapse rates of 0.6%, 3.4% and 10.2% respectively. In high risk patients, CNS dissemination is responsible for up to 1/3 of lymphoma related deaths. In addition to the CNS-IPI there is additional prognostic impact of the number of extra-nodal sites of lymphoma at diagnosis and have identified additional specific high risk site of extra-nodal involvement (for example, uterine involvement). Selected anatomical sites, despite low CNS-IPI score, are also reported to have higher rates of CNS relapse; including testis with reported 5-year rates of CNS relapse of 15%, and breast with 5.5 year CNS relapse rates of 5.5%\nDespite the CNS-IPI score there remains little consensus as to which patients are truly ‘high risk’ and therefore which patients should be offered CNS prophylaxis, what therapy they should be offered (eg. Intrathecal vs high dose intravenous methotrexate), and how treatment should be incorporated into systemic lymphoma therapy (eg. Intercalated with frontline immunochemotherapy or administered following completion of immunochemotherapy).Since CNS relapse in aggressive lymphoma remains an uncommon event, large datasets are required to detect significant differences between prophylactic approaches. Data investigating the effectiveness of different CNS prophylactic interventions at reducing relapse remain scarce, and international practice varies widely. This study will assess the effectiveness of CNS prophylaxis in patients with high risk of CNS relapse.\n\nResults\nPatients with aggressive B-cell lymphoma have a risk of disease spreading to the brain or spinal cord (central nervous system, [CNS]). CNS progression or relapse is uncommon but devastating when it happens. There is no consensus regarding the best way to prevent this complication. High-dose methotrexate (HD-MTX) is frequently used to try and prevent this complication however there is limited evidence that it is effective, and it also has significant toxicities of its own.\nThis study was designed to determine whether HD-MTX is effective at preventing CNS progression in patients at higher risk of this complication. In this study of 2418 high-risk patients the use of HD-MTX did not result in a clinically meaningful reduction in the risk of CNS progression.
REC name
North of Scotland Research Ethics Committee 1
REC reference
21/NS/0021
Date of REC Opinion
12 Feb 2021
REC opinion
Favourable Opinion