Final results of a multicenter trial addressing role of CSF flow cytometric analysis in NHL patients at high risk for CNS dissemination

This prospective study compared diagnostic and prognostic value of conventional cytologic examination (CC) and flow cytometry (FCM) of baseline samples of cerebrospinal fluid in 174 patients with newly diagnosed aggressive NHL. FCM detected a neoplastic population in the CSF of 18 out of 174 patients (10%), CC only in 7 (4%) (p< 0.001); 11 patients (14%) were discordant (FCM+/CC-). At a median follow up of 46 months, there were 64 systemic progressions, 10 CNS relapses, including two patients with both systemic and CNS relapse. Two-year PFS and OS were significantly higher in patients with FCM-negative CSF (62% and 72%) compared with those FCMpositive CSF (39% and 50%) with a 2-year CNS relapse cumulative incidence of 3%(95%CI:0-7) vs.17%(95%CI:0-34)(p= 0.004), respectively. Discordant patients showed a significant increased risk of CNS progression at 2-year respect to both negative patients (HR 8.16, 95%CI:1.45-46). In conclusion, FCM positivity in CSF of patients with high-risk NHL is associated with a significantly higher CNS relapse risk and poorer outcome. Brain parenchyma was the commonest site of CNS failure, suggesting that the combination of i.v drugs with a higher CNS bioavailability and intrathecal chemotherapy is advisable to prevent CNS relapses in FCM+ patients.