Originally published as JCO Early Release 10.1200/JCO.2008.17.7089 on February 17 2009

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Identification of Leptomeningeal Disease in Aggressive B-Cell Non-Hodgkin's Lymphoma: Improved Sensitivity of Flow Cytometry

From the Servicio General de Citometría, Department of Medicine and Centro de Investigación del Cáncer (CIC; USAL/CSIC), Universidad de Salamanca, Salamanca; Servicio de Hematología, Hospital Universitario Germans Trias I Pujol Badalona, Universidad Autónoma de Barcelona; Servicio de Hematología, Clínica Universitaria de Navarra, Pamplona; Servicio de Hematología, Hospital Juan Canalejo, La Coruña; Servicio de Hematología, Hospital Morales Meseguer, Murcia; Servicio de Hematología, Hospital Universitario de Getafe; Servicio de Hematología, Fundación Hospital Alcorcón; Servicio de Hematología, Hospital La Paz; Servicio de Hematología, Hospital Puerta de Hierro; Servicio de Hematología, Hospital Sant Pau, Barcelona, Madrid; Servicio de Hematología, Hospital del Mar; Servicio de Hematología, Instituto Catalán de Oncología, Barcelona; Servicio de Hematología, Compleyo Hospitalario Universitario de Santiago, Santiago de Compostela; Servicio de Hematología, Hospital Xeral-Cies, Vigo; Servicio de Hematología, Hospital Xeral Calde, Lugo; Servicio de Hematología, Fundación Hospital Doctor Peset, Valencia; Servicio de Hematología, Hospital Puerta del Mar, Cádiz; Servicio de Hematología, Hospital Central de Asturias, Oviedo, Spain.

Corresponding author: Alberto Orfao, MD, PhD, Servicio General de Citometría, Laboratorio de Hematología Hospital Universitario Salamanca, Paseo de San Vicente, 58-182, 37007 Salamanca, Spain; e-mail: orfao{at}usal.es.

Purpose Here, we evaluate the sensitivity and specificity of a new 11-parameter flow cytometry (FCM) approach versus conventional cytology (CC) for detecting neoplastic cells in stabilized CSF samples from newly diagnosed aggressive B-cell non-Hodgkin's lymphoma (B-NHL) at high risk of CNS relapse, using a prospective, multicentric study design.

Patients and Methods Moreover, we compared the distribution of different subpopulations of CSF leukocytes and the clinico-biologic characteristics of CSF+ versus CSF–, patients, in an attempt to define new algorithms useful for predicting CNS disease.

Results Overall, 27 (22%) of 123 patients showed infiltration by FCM, while CC was positive in only seven patients (6%), with three other cases being suspicious (2%). CC+/FCM+ samples typically had more than 20% neoplastic B cells and/or one neoplastic B cell/µL, while FCM+/CC– samples showed lower levels (P < .0001) of infiltration. Interestingly, in Burkitt lymphoma, presence of CNS disease by FCM could be predicted with a high specificity when increased serum β2-microglobulin and neurological symptoms coexisted, while peripheral blood involvement was the only independent parameter associated with CNS disease in diffuse large B-cell lymphoma, with low predictive value.

Conclusion FCM significantly improves the sensitivity of CC for the identification of leptomeningeal disease in aggressive B-NHL at higher risk of CNS disease, particularly in paucicellular samples.

Written on behalf of the Spanish Group for the Study of CNS Disease in NHL.

Supported by Grant No. FIS 06/0824 from the Ministerio de Sanidad y Consumo, Madrid, Spain, and Grant No. RETICC RD06/0020/0035 from the Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain; by the "Acción Transversal del Cáncer" project, through an agreement between instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation (Madrid, Spain), and the Cancer Research Foundation of the University of Salamanca (Salamanca, Spain); by Mundipharma Pharmaceuticals, SL (Madrid, Spain); and by a grant from COLCIENCIAS, Bogotá-Colombia (S.Q.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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