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Background and Aim: 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., Patients and 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., (© 2010 John Wiley & Sons A/S.)

Background and Objective: Central nervous system (CNS) involvement in patients diagnosed with non-Hodgkin's lymphoma (NHL) or other lymphoproliferative disorders is an infrequent complication with a poor prognosis. The prophylaxis and treatment of CNS involvement in these patients are not homogenous. The aim of this prospective longitudinal study was to report the current practice of CNS prophylaxis and treatment in patients with lymphoproliferative disorders in Spain., Methods: Prospective study conducted from June 2005 to June 2006. Adult patients (> or = 18 yr) diagnosed with NHL or other lymphoproliferative disorders who received CNS prophylaxis or treatment were consecutively included through online registration., Results: 228 patients from 33 hospitals were included. The mean (SD) age was 52 (16) yr and 144 (63%) were males. CNS therapy was given to 41 cases and consisted of triple intrathecal (IT) therapy (TIT, methotrexate, cytarabine and hydrocortisone) in 22, liposomal depot cytarabine in 18 and methotrexate in one. In addition, 4 patients received cranial radiotherapy. CNS prophylaxis (n = 187) consisted of TIT (166 cases), IT methotrexate (17), IT liposomal depot cytarabine (3) and IT cytarabine (1), whereas cranial or craniospinal radiotherapy was administered to 2 patients. The main reasons for CNS prophylaxis cited by the investigators included extranodal involvement (89 patients), raised serum lactate dehydrogenase level (87), IPI score > 2 (62), bulky mass (43), extranodal involvement in more than one organ (33), age over 60 yr (28) and human immunodeficiency virus infection (13)., Conclusions: The results of this study point out the generalized use of TIT therapy both for CNS prophylaxis and therapy in patients with lymphoproliferative disorders in Spain. The introduction of the new formulations of drugs, especially liposomal depot cytarabine for CNS involvement, and the scarce use of radiotherapy are also of note. Similar to other studies, the absence of homogeneous criteria for CNS prophylaxis is of note.

Background and Objective: Central nervous system (CNS) involvement in patients diagnosed with acute leukemias (AL) is an uncommon complication with poor prognosis. The indication and the schedules of prophylaxis and treatment of CNS involvement in AL are not homogenous among countries and within the same country. The aim of this prospective longitudinal study was to analyze and report the practice of CNS prophylaxis and treatment in patients with AL in Spain., Patients and Method: Prospective study conducted from June 2005 to June 2006. Adult patients (> or = 18 yr.) diagnosed with AL who received CNS prophylaxis or treatment were consecutively included through online registration., Results: 265 patients from 32 hospitals were included. Mean (standard deviation) age was 44 (16) yr. and 133 (50%) were males. For acute lymphoblastic leukemia patients (n = 158), CNS therapy was given to 12 cases (10 at diagnosis and 2 at relapse) and consisted of triple intrathecal therapy (TIT, methotrexate, cytarabine and hydrocortisone) in 11 and liposomal depot cytarabine in one. CNS prophylaxis (n = 146) consisted of TIT in 135 cases, intrathecal methotrexate in 7, intrathecal cytarabine in 2 and intrathecal liposomal depot cytarabine in 2. No cranial irradiation either for prophylaxis or therapy was given in any case. In acute myeloblastic leukemia patients (n = 107), CNS therapy was administered to 17 cases (9 at diagnosis and 8 at relapse). Intrathecal therapy consisted of TIT in 11, intrathecal liposomal depot cytarabine in 5 and intrathecal cytarabine in one. One patient also received craniospinal irradiation. CNS prophylaxis (n = 90) consisted of TIT in 68 cases and intrathecal methotrexate in 22., Conclusions: In Spain, the patterns of CNS prophylaxis and therapy for AL are homogeneous. TIT was the most frequent schedule for CNS prophylaxis and therapy. The lack of use of cranial or craniospinal irradiation and the administration of new drugs (i.e.: liposomal depot cytarabine) for CNS therapy and prophylaxis is of note.

Recurrence of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) confers a poor prognosis, although to the authors' knowledge, only a few studies have analyzed this issue in adults. For the current study, the authors analyzed the frequency, predictive factors, and prognosis of CNS involvement and recurrence in adult patients with ALL who did not receive cranial irradiation for CNS prophylaxis. Four hundred sixty-seven adult patients (age > or = 15 years) with ALL were treated on 4 protocols: ALL-89 (standard-risk and high-risk ALL; n = 108 patients), ALL-93 (high-risk ALL; n = 222 patients), ALL-96 (standard-risk ALL; n = 84 patients), and ALL3-97 (Burkitt leukemia; n = 53 patients). CNS prophylaxis consisted of intrathecal methotrexate, cytarabine, and hydrocortisone together with high-dose systemic methotrexate and cytarabine. The mean age (+/- standard deviation) was 33 years (+/- 16 years), and 272 patients were males. ALL subtypes included an early pre-B phenotype (15%), a common phenotype (45%), a pre-B phenotype (5%), a mature B phenotype (11%), and a T phenotype (24%). CNS involvement at diagnosis was observed in 18 patients (3.9%). Of 159 recurrences, 22 occurred (5.8%) in the CNS (14 isolated and 8 combined). A lactate dehydrogenase level > 1000 U/L was the only factor associated with the risk of CNS recurrence. A complete remission was attained in 7 of 22 patients (32%). The median overall survival after recurrence was 0.7 years for patients with isolated CNS recurrence, 0.13 years for patients with combined recurrence, and 0.41 years for patients with bone marrow recurrence (P = .11). The only 2 survivors underwent stem cell transplantation. The frequency of CNS recurrence in adult patients with ALL who do not receive radiotherapy for CNS prophylaxis was similar to the frequency observed in protocols that included cranial irradiation. A lactate dehydrogenase value >1000 U/L was the only factor found to be associated with CNS recurrence. The prognosis for patients who develop CNS recurrence is poor, identical to that for patients who develop bone marrow recurrence., (Copyright 2006 American Cancer Society.)