ABSTRACT
BACKGROUND: We evaluated the frequency and prognostic impact of meningeal dissemination (MD) in immunocompetent adult patients with primary central nervous system lymphoma treated in a randomized phase III trial. PATIENTS AND METHODS: MD was evaluated at study entry and defined by lymphoma proof in the meningeal compartment detected by at least one of the following methods: cerebrospinal fluid (CSF) cytomorphology, detection of clonal B cells by IgH PCR in CSF or contrast enhancement of the leptomeninges on magnetic resonance imaging (MRI). RESULTS: Data on MD were available in 415 patients, of those, MD was detected in 65 (15.7%): in 44/361 (12.2%) by CSF cytomorphology, in 16/152 (10.5%) by PCR and in 17/415 (4.1%) by MRI. Major patients' characteristics and therapy did not significantly differ between patients with MD (MD+) versus those without MD (MD-). There was a significant correlation of MD with CSF pleocytosis (>5/µl; P < 0.0001), but no correlation with CSF protein elevation (>45 mg/dl). Median progression-free survival was 6.7 months [95% confidence interval (CI) 0-14.5] in MD+ and 8.3 months (5.7-10.8) in MD- patients (P = 0.95); median overall survival was 21.5 months (95% CI 16.8-26.1) and 24.9 months (17.5-32.3), respectively (P = 0.98). CONCLUSION: MD was detected infrequently and had no impact on outcome in this trial.
Subject(s)
Central Nervous System Neoplasms/pathology , Meningeal Neoplasms/secondary , Adult , Aged , Aged, 80 and over , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/mortality , Central Nervous System Neoplasms/therapy , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Lymphoma , Male , Meningeal Neoplasms/cerebrospinal fluid , Meningeal Neoplasms/mortality , Meningeal Neoplasms/therapy , Middle Aged , Prognosis , Randomized Controlled Trials as Topic , Young AdultABSTRACT
BACKGROUND: The impact of meningeal dissemination in primary CNS lymphoma (PCNSL) is debated, and the reported frequency varies. We prospectively evaluated the diagnostic value of PCR in comparison with CSF cytomorphology and MRI for diagnosing meningeal dissemination in PCNSL. METHODS: We evaluated 282 patients from a multicenter therapy study for PCNSL for the presence of meningeal dissemination: 205 with CSF cytomorphology, 171 with PCR of the rearranged immunoglobulin heavy-chain genes in CSF, and 217 with cranial MRI. RESULTS: Meningeal dissemination was found in 33 of 205 patients (16%) by cytomorphology, in 19 of 171 (11%) patients evaluated by PCR, and in 8 of 217 patients (4%) by MRI. Considering either of these methods, the relative frequency of meningeal dissemination was 17.4% (49 of 282 patients). PCR was monoclonal in 6 of 19 (32%) samples with positive cytomorphology, 1 of 13 samples (8%) with suspicious cytology, and in 10 of 105 (10%) cytologically negative samples. In 11 samples with positive and 12 with suspicious cytology, PCR showed only a polyclonal pattern. The probability of meningeal dissemination detection was higher in cases with CSF pleocytosis (>5/microL) with an OR of 2.48 (95% CI 1.15-5.34, p = 0.018). CSF protein had no predictive value for meningeal dissemination detection. CONCLUSIONS: We found a low rate of meningeal dissemination in primary CNS lymphoma in this large prospective study. The rate of discordant PCR and cytomorphologic results was high. Thus, the methods should be regarded as complementary. CSF pleocytosis had predictive value for meningeal dissemination detection.
Subject(s)
Lymphoma/diagnosis , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/secondary , Neoplasm Metastasis/diagnosis , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain/pathology , Cell Count/statistics & numerical data , Combined Modality Therapy , Cytological Techniques/statistics & numerical data , Female , Humans , Immunoglobulin Heavy Chains/analysis , Immunoglobulin Heavy Chains/blood , Lymphoma/immunology , Lymphoma/therapy , Magnetic Resonance Imaging/statistics & numerical data , Male , Meningeal Neoplasms/immunology , Meninges/pathology , Middle Aged , Neoplasm Metastasis/immunology , Polymerase Chain Reaction/statistics & numerical data , Predictive Value of Tests , Prospective Studies , Reproducibility of ResultsABSTRACT
BACKGROUND: Standard salvage therapy has not been established for recurrent primary central nervous system lymphoma (PCNSL). We report the final results of a prospective study on topotecan chemotherapy in relapsed or refractory PCNSL. PATIENTS AND METHODS: The study included 27 patients with a median age of 51 years and an ECOG performance status of 2. Fourteen patients were refractory to the last therapy, and 13 relapsed after a median period of 6.0 months. Pretreatment with up to four regimens included chemotherapy in 26 patients and whole brain irradiation in 14. A 30-min daily topotecan infusion of 1.5 mg/m(2) for 5 days was repeated every 3 weeks. RESULTS: The response rate was 33% with five complete (CR) and four partial remissions (PR). The median follow-up was 37.7 months. All complete responders had sustained remissions lasting for 9 to 28 months. The median event-free survival (EFS) was 2.0 months (9.1 months in responders), the overall survival (OAS) was 8.4 months. CTC grade 3-4 leukopenia occurred in 26% and thrombocytopenia in 11% of the patients. Eight of 12 patients alive without cerebral lymphoma > or = six months after topotecan exhibited deficits attributable to late neurotoxicity. CONCLUSION: Topotecan as monotherapy is active in relapsed and refractory PCNSL with tolerable toxicity.
Subject(s)
Antineoplastic Agents/therapeutic use , Central Nervous System Neoplasms/drug therapy , Lymphoma/drug therapy , Salvage Therapy , Topotecan/therapeutic use , Adult , Aged , Central Nervous System Neoplasms/mortality , Central Nervous System Neoplasms/radiotherapy , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Lymphoma/mortality , Lymphoma/radiotherapy , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Prospective Studies , Remission Induction , Survival AnalysisABSTRACT
The authors treated 16 immunocompetent patients with refractory or relapsed primary CNS lymphoma with topotecan. Fifteen patients had been pretreated with up to three chemotherapy regimens, three of them additionally with whole brain irradiation (WBI), and one with WBI alone. Four complete remissions and two partial remissions were achieved. Progression-free survival was 20% at 6 months and 13% at 12 months.
