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Role of CNS intrathecal prophylaxis in DLBCL
Figure 1. PRISMA Flow diagram of search strategy and inclusion/exclusion.
patients often were at higher risk of relapse than patients not receiving IT prophylaxis. Univariable analysis was performed in all studies and no study demonstrated clear evidence of a reduction in the risk of CNS relapse when IT prophylaxis was used. Multivariable analyses were per- formed and described in nine studies (Tables 3A-C). IT prophylaxis was not found to be a univariable or multi- variable factor associated with a statistically significant reduction in the risk of CNS relapse in any of the studies examined.
No adjusted analyses were described in one study.28 Adjusted analyses were reported in the remaining four studies in a variety of forms 1. Adjustment for CNS-IPI (n=2);24,27 2. Propensity matching to analyse survival (pro- gression-free and overall survival) but not CNS relapse (n=1);29 3. Proportional hazard ratio to assess interaction between rituximab and IT prophylaxis with a univari- able/multivariable analysis looking at clinical risk factors
associated with CNS relapse and not IT prophylaxis (n=1).30 None of these adjusted analyses showed that IT prophylaxis provided any benefit in reducing the risk of CNS relapse in the anti-CD20 antibody era.
Of note, no individual analysis reported the morbidity associated with IT prophylaxis in terms of the risk of adverse events, for example, risk of systemic infection, post lumbar puncture headache or dural leak.
Quality and statistical appraisal
We identified a range of study types including post hoc analyses of randomised clinical trials, prospective and ret- rospective cohort studies. None of the studies prospective- ly asked whether CNS IT stand-alone prophylaxis reduces the rate of CNS relapse. Although the absolute number of patients included within each study was relatively large, the absolute event number across studies was low. As a result, the statistical power within each study to provide
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