Clinical significance of occult cerebrospinal fluid involvement assessed by flow cytometry in non-Hodgkin's lymphoma patients at high risk of central nervous system disease in the rituximab era.
OBJECTIVE
Flow cytometry (FCM) analysis of cerebrospinal fluid (CSF) is more sensitive than conventional cytology (CC) for diagnosis of lymphomatous meningeosis, but the clinical significance of occult central nervous system (CNS) disease (positive FCM with negative CC) remains unknown.


METHODS
CSF samples from 105 patients with newly diagnosed aggressive lymphomas at high risk of CNS involvement were prospectively studied by both CC and FCM, and results were correlated with cumulative incidence of CNS relapse and overall survival (OS). Patients were divided into three groups: 1) patients without CNS involvement (CC-/FCM-; n=83); 2) individuals with occult CNS disease (FCM+/CC-; n=15); and 3) cases with CNS disease (CC+/FCM+; n=7).


RESULTS
Six cases showed CNS relapse or progression: two in Group 1 (2.4%), two in Group 2 (13%) and two in Group 3 (28.5%) (Group 2 vs. 1, P=0.04; Group 3 vs. 1, P<0.001). Patients from Groups 2 (P=0.05) and 3 (P<0.001) also showed a higher cumulative incidence of CNS relapse than those from Group 1. Significant differences were observed in OS between FCM-/CC- and FCM+/CC+ cases (P=0.02), while patients with occult CNS disease (FCM+/CC-) displayed intermediate OS rates, although differences did not reach statistical significance.


CONCLUSIONS
The presence of occult CNS involvement at diagnosis in patients with NHL at high risk of CNS disease is associated with a higher probability of CNS relapse.
Clinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Spain.
Juan-Manuel
JM
Sancho
Alberto
A
Orfao
Sandra
S
Quijano
Olga
O
García
Carlos
C
Panizo
Elena
E
Pérez-Ceballos
Guillermo
G
Deben
Antonio
A
Salar
Eva
E
González-Barca
Natalia
N
Alonso
Jose-Antonio
JA
García-Vela
Javier
J
Capote
Francisco-Javier
FJ
Peñalver
Mariano
M
Provencio
Jesús
J
Arias
Josefa
J
Plaza
Dolores
D
Caballero
Marta
M
Morado
Evarist
E
Feliu
Josep-Maria
JM
Ribera
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid / Q000150:complications / Q000175:diagnosis; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000134:cerebrospinal fluid* / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008853:Microscopy / Q000379:methods; D008875:Middle Aged; D011237:Predictive Value of Tests; D012008:Recurrence; D012307:Risk Factors; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab