Clinical Significance of the Presence of Occult CNS Involvement Assessed by Cytofluorometry in Patients with Non Hodgkin’s Lymphoma and High Risk of CNS Relapse

Background and objective. Several studies have demonstrated that flow cytometry (FCM) improves the sensitivity of conventional cytology (CC) for the identification of leptomeningeal disease in aggressive lymphomas with high risk of central nervous system (CNS) involvement. A previous report from our group showed infiltration by FCM study in 27 out of 123 (22%) newly diagnosed aggressive B-cell lymphomas, while CC was positive in only 7 (6%). However, the clinical significance of the occult disease in CNS (FCM positive and CC negative) remains unknown.

Patients and Methods. At the time of the analysis, 68 out of 123 patients of the previous study had adequate follow-up (median of follow-up for the alive patients [n=42] of 18 months [range 12–30]). In this cohort of patients the CNS involvement during follow-up was assessed according to CC and FCM results in cerebrospinal fluid at the time of diagnosis.

Results. Three groups were defined according to the results of CC and CFM: Group 1, patients without CNS involvement (CC and FCM negatives, n=49); Group 2, patients with occult CNS disease (FCM positive and CC negative, n=11); Group 3, patients with CNS disease (CC and FCM positive, n=8). The groups were comparable for the main clinical and biological characteristics and histological subtypes of NHL. In the Group 1, 40 patients received intrathecal (IT) prophylaxis, 2 received CNS therapy due to the presence neurological symptoms and 7 did not receive any prophylaxis. In the Group 2, CNS prophylaxis was administered to 7 patients, whereas the 4 remaining received active therapy. The 8 patients of the Group 3 received active CNS therapy. Overall, 6 patients showed CNS relapse/progression, 2 in the Group 1 (4.1%) (both with diffuse large B cell lymphoma [DLBCL]) and 4 in the Group 3 (50%) (3 with Burkitt’s lymphoma and the remaining with DLBCL). None of the patients of the Group 2 showed CNS relapse or progression during follow-up. As expected, patients of Group 3 showed a significant increase in CNS relapse compared to those from Groups 1 (p<0.001) and 2 (p=0.038). However, the incidence of CNS relapse in patients of Groups 1 and 2 was not statistically different (p=0.496).

Conclusions. Up to now, and different from previous studies, the presence of occult CNS disease in our cohort of patients with NHL and high risk of CNS disease was not associated with a higher risk of CNS relapse. This feature could be due to the fact that most of the patients received adequate CNS prophylaxis, that could be sufficient to eliminate the occult disease.