Primary intraocular lymphoma (PIOL): An International Primary CNS Lymphoma Collaborative group report

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1534-1534
Author(s):  
S. Grimm ◽  
J. Pulido ◽  
K. Jahnke ◽  
D. Schiff ◽  
A. Hall ◽  
...  
Keyword(s):  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Local Therapy ◽  
Initial Therapy ◽  
Collaborative Group ◽  
Intraocular Lymphoma ◽  
Cns Lymphoma ◽  
Treatment Type ◽  
Increased Risk ◽  
Sites Of Relapse

1534 Background: PIOL is a hemopoietic tumor that arises in the retina, vitreous or optic nerve head, and carries a high risk of ocular and CNS relapse. The natural history and optimal management are unknown. Methods: A retrospective series of 81 patients with PIOL was assembled from 15 centers in 7 countries. Only patients with isolated ocular lymphoma were included; none had brain, spinal cord, or systemic lymphoma at diagnosis. Results: The median age at diagnosis was 65 (24–85). 58% were women. The median ECOG performance status was 0, and only three had a score > 1. The median latency from symptom onset to diagnosis was 6 months (0– 36). Slit lamp exam was positive in 51, negative in 6, and not reported in 24. Vitrectomy was positive in 72 and negative in 2. 6 had a positive choroidal or retinal biopsy and 1 had no ocular surgery. CSF cytology was positive in 10 (17%), negative in 48, and unknown in 23. 21 received local therapy at diagnosis: 6 intra-ocular methotrexate (400 ug), 14 ocular radiation (median 3600 cGy), and 1 both modalities. 52 received more extensive therapy including systemic chemotherapy alone in 20 and a combination of chemotherapy and radiotherapy in 32. 5 received no treatment and details are unknown in 3. 47 patients (58%) relapsed a median of 19 months (0.5–180) after initial therapy. Sites of relapse included brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Patients treated with ocular therapy alone did not have an increased risk of failing in the brain (p = 0.6). Progression free survival (PFS) and overall survival (OS) were 29.6 and 57 months respectively and were unaffected by the choice of therapy. CNS disease was the cause of death in 19/33 (58%). Conclusions: In this series, treatment type did not affect sites of relapse, PFS or OS in patients with PIOL. To minimize toxicity, the best initial therapy should be limited to intraocular chemotherapy or focal radiotherapy. Prospective clinical trials are needed to improve our understanding and treatment of this disease. No significant financial relationships to disclose.

Primary CNS Lymphoma of T-Cell Origin: A Descriptive Analysis From the International Primary CNS Lymphoma Collaborative Group

2005 ◽  
Vol 23 (10) ◽  
pp. 2233-2239 ◽  
Author(s):  
Tamara N. Shenkier ◽  
Jean-Yves Blay ◽  
Brian Patrick O’Neill ◽  
Philip Poortmans ◽  
Eckhard Thiel ◽  
...  
Keyword(s):  
T Cell ◽  
Performance Status ◽  
Descriptive Analysis ◽  
Eastern Cooperative Oncology Group ◽  
Primary Cns Lymphoma ◽  
Serum Lactate ◽  
Collaborative Group ◽  
Serum Lactate Dehydrogenase ◽  
Cns Lymphoma ◽  
Ecog Performance Status

Purpose To describe the demographic and tumor related characteristics and outcomes for patients with primary T-cell CNS lymphoma (TPCNSL). Patients and Methods A retrospective series of patients with TPCNSL was compiled from twelve cancer centers in seven countries. Results We identified 45 patients with a median age of 60 years (range, 3 to 84 years). Twenty (44%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Twenty-six (58%) had involvement of a cerebral hemisphere and sixteen (36%) had lesions of deeper sites in the brain. Serum lactate dehydrogenase was elevated in 7 (32%) of 22 patients, and CSF protein was elevated in 19 of 24 patients (79%) with available data. The median disease-specific survival (DSS) was 25 months (95% CI, 11 to 38 months). The 2- and 5-year DSS were 51% (95% CI, 35% to 66%) and 17% (95% CI, 6% to 34%), respectively. Univariate and multivariate analyses were conducted for age (≤ 60 v > 60 years), PS (0 or 1 v 2, 3, or 4), involvement of deep structures of the CNS (no v yes), and methotrexate (MTX) use in the primary treatment (yes v no). Only PS and MTX use were significantly associated with better outcome with hazard ratios of 0.2 (95% CI, 0.1 to 0.4) and 0.4 (95% CI, 0.2 to 0.8), respectively. Conclusion This is the largest series ever assembled of TPCNSL. The presentation and outcome appear similar to that of B cell PCNSL. PS 0 or 1 and administration of MTX are associated with better survival.

Importance of Radiotherapy in the Outcome of Patients With Primary CNS Lymphoma: An Analysis of the CHOD/BVAM Regimen Followed by Two Different Radiotherapy Treatments

2002 ◽  
Vol 20 (1) ◽  
pp. 231-236 ◽  
Author(s):  
E. M. Bessell ◽  
A. López-Guillermo ◽  
S. Villá ◽  
E. Verger ◽  
B. Nomdedeu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Complete Response ◽  
Cns Lymphoma ◽  
Reduced Dose ◽  
Increased Risk ◽  
Risk Of Relapse ◽  
All Treatment

PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS: Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS: Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P = .01). The 5-year overall survival (OS) was 36%. Age (< 60 v ≥ 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P = .04). CONCLUSION: Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS.

Treatment of Primary CNS Lymphoma in the Elderly, a Multicenter Retrospective Analysis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3591-3591
Author(s):  
Jacoline E.C. Bromberg ◽  
Jeanette Doorduyn ◽  
Macha Schuurmans ◽  
Philip Poortmans ◽  
Martin J.B. Taphoorn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Performance Status ◽  
Primary Cns Lymphoma ◽  
The Elderly ◽  
Cns Lymphoma ◽  
Combined Modality Treatment ◽  
Significant Prognostic Factor ◽  
Adequate Treatment ◽  
Increased Risk

Abstract Patients with primary CNS lymphoma (PCNSL) are preferably treated with high-dose Methotrexate (HD-MTX)-based chemotherapy followed by consolidation radiotherapy in many centers. As elderly patients have an increased risk of complications with this approach, they are frequently treated with chemotherapy or radiotherapy alone. Little is known about the efficacy and toxicity of either of these treatments in elderly patients outside clinical studies. We analysed all patients aged 60 or above referred with PCNSL to 5 Dutch centers between 1998 and 2007. 110 patients were identified. We excluded: patients who were not treated because of a poor condition (n=25), patients with EBVrelated NHL (n=3), patients with PCNSL confined to the eyes (n=3), and patients with missing information on follow-up (n=5). The remaining 74 patients had a median age of 65 years (range 60–82), and a median KPS of 70% (range 30–100). Twenty-nine of them were treated with radiotherapy only, 19 with chemotherapy only and 26 with both; 19 of these 26 received radiotherapy after failure of chemotherapy. Median KPS was 70 in both single treatment modality groups and 80 in the group receiving both modalities. The response rate (CR or PR) was 69% (20/29) in patients treated with radiotherapy only and 63% (12/19) in patients treated with chemotherapy only. Timing of both response evaluation and radiotherapy after chemotherapy were highly variable in the group treated with both modalities, therefore these patients are only included in the overall survival analyses. Median overall survival (OS) was 20 months: 7 months for patients treated with radiotherapy only, 23 months for those treated with chemotherapy only, and 31 months for combined modality treatment (p=0.01). The KPS was a significant prognostic factor for as well PFS as OS (p<0.001): median PFS and OS were 3 and 4 months respectively in patients with KPS < 70 and 18 and 25 months in patients with a KPS ≥ 70. Forty of the 45 patients receiving chemotherapy were planned for treatment with a MTX dose of 3g/m2. There were 2 toxic deaths. Ten of the 40 patients received delayed or reduced doses, or aborted chemotherapy because of toxicity. Delayed encephalopathy was reported in 15 patients: 7/30 patients after radiotherapy, 1/19 after chemotherapy only and 7/26 after combined treatment. Five died as a consequence of the encephalopathy. Conclusion: Performance status is the most important single variable determining prognosis in elderly patients. Overall survival after HD-MTX-based treatment for PCNSL in the elderly appears to approach survival obtained in younger patients, provided the performance status is adequate. Treatment related mortality of HD-MTX-based chemotherapy seems not to be increased in older patients.

scholarly journals Consensus Recommendations for MRI and PET Imaging of Primary Central Nervous System Lymphoma: Guideline Statement from the International Primary CNS Lymphoma Collaborative Group (IPCG)

2021 ◽  
Author(s):  
Ramon F Barajas Jr ◽  
Letterio S Politi ◽  
Nicoletta Anzalone ◽  
Heiko Schöder ◽  
Christopher P Fox ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Imaging ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Response Assessment ◽  
Integrated Approach ◽  
Collaborative Group ◽  
Cns Lymphoma ◽  
Consensus Recommendations

Abstract Advanced molecular and pathophysiologic characterization of Primary Central Nervous System Lymphoma (PCNSL) has revealed insights into promising targeted therapeutic approaches. Medical imaging plays a fundamental role in PCNSL diagnosis, staging, and response assessment. Institutional imaging variation and inconsistent clinical trial reporting diminishes the reliability and reproducibility of clinical response assessment. In this context, we aimed to: 1) critically review the use of advanced PET and MRI in the setting of PCNSL; 2) provide results from an international survey of clinical sites describing the current practices for routine and advanced imaging, and 3) provide biologically based recommendations from the International PCNSL Collaborative Group (IPCG) on adaptation of standardized imaging practices. The IPCG provides PET and MRI consensus recommendations built upon previous recommendations for standardized brain tumor imaging protocols (BTIP) in primary and metastatic disease. A biologically integrated approach is provided to addresses the unique challenges associated with the imaging assessment of PCNSL. Detailed imaging parameters facilitate the adoption of these recommendations by researchers and clinicians. To enhance clinical feasibility, we have developed both “ideal” and “minimum standard” protocols at 3T and 1.5T MR systems that will facilitate widespread adoption.

How I treat primary CNS lymphoma

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 510-522 ◽  
Author(s):  
Andrés J. M. Ferreri
Keyword(s):  
Molecular Mechanisms ◽  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Poor Performance ◽  
Cns Lymphoma ◽  
Poor Performance Status ◽  
Level Of Evidence ◽  
Therapeutic Decisions ◽  
New Ideas ◽  
Rare Malignancy

Abstract Primary CNS lymphoma (PCNSL) is a rare malignancy with peculiar clinical and biologic features, aggressive course, and unsatisfactory outcome. It represents a challenge for multidisciplinary clinicians and scientists as therapeutic progress is inhibited by several issues. Molecular and biologic knowledge is incomplete, limiting the identification of new therapeutic targets, and the particular microenvironment of this malignancy, and sanctuary sites where tumor cells grow undisturbed, strongly affects treatment efficacy. Moreover, active treatments are known to be associated with disabling neurotoxicity, posing the dilemma of whether to intensify therapy to improve the cure rate or to de-escalate treatment to avoid sequels. The execution of prospective trials is also difficult because of the rarity of the tumor and the impaired general condition and poor performance status of patients. Thus, level of evidence is low, with consequent uncertainties in therapeutic decisions and lack of consensus on primary endpoints for future trials. Despite this unfavorable background, laboratory and clinical researchers are coordinating efforts to develop new ideas, resulting in the recent publication of studies on PCNSL's biology and molecular mechanisms and of the first international randomized trials. Herein, these important contributions are analyzed to provide recommendations for everyday practice and the rationale for future trials.

scholarly journals Management and outcome of primary CNS lymphoma in the modern era

Neurology ◽  
2020 ◽  
Vol 94 (10) ◽  
pp. e1027-e1039 ◽  
Author(s):  
Caroline Houillier ◽  
Carole Soussain ◽  
Hervé Ghesquières ◽  
Pierre Soubeyran ◽  
Olivier Chinot ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Real Life ◽  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Population Based ◽  
Cns Lymphoma ◽  
High Dose ◽  
Population Based Study

ObjectiveReal-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL.MethodsThe French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed.ResultsWe identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients <60 years of age received consolidation treatment in 77% of cases, consisting of whole-brain radiotherapy (WBRT) (54%) or high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) (23%). Among patients >60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (<60 years: not reached [NR], 70%, and 61%; >60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis.ConclusionsOur study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.

scholarly journals NQPC-5 Does high-dose methotrexate-based chemotherapy for relapsed primary CNS lymphoma increase a risk of leukoencephalopathy with prior whole brain radiotherapy?

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi22-vi22
Author(s):  
Keiichi Kobayashi ◽  
Nobuyoshi Sasaki ◽  
Kuniaki Saito ◽  
Yuki Yamagishi ◽  
Naomi Hanayama ◽  
...  
Keyword(s):  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Study Results

Abstract Backgrounds: Standard care for primary central nervous system lymphoma (PCNSL) comprises high-dose (HD) methotrexate (MTX) -based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). HD-MTX administration following WBRT has been suggested to increase a risk of leukoencephalopathy. However, given that there are no other agents with efficacy similar to or better than MTX, patients with relapsed PCNSL may often be treated with regimens containing HD-MTX if the initial MTX treatment achieved a long-term complete remission. Here, we retrospectively analyzed prevalence and an extent of white mater damages in association with prior WBRT in patients with relapsed PCNSL treated with HD-MTX based therapy. Patients & methods: Among 79 patients with relapsed/refractory PCNSL in a total of 162 patients with newly-diagnosed PCNSL treated in our institution from April, 2000 to February, 2021, 35 patients were identified with evaluable KPS, MMSE, and Fazekas scale data at both baseline and follow-up periods. Of the 35 patients, 22 were treated with chemotherapy at a relapse (10 with prior WBRT, while 12 without WBRT), and were included in this preliminary study. Results: In the WBRT group (male/female: 5/5), median age was 65 years (range, 45–73), initial median KPS was 70 (40–90), and median WBRT dose was 27 Gy (23.4–40). Median progression-free survival (mPFS) was 11.8 months, and median overall survival (mOS) was not reached. In the non-WBRT group (M/F 8/4), median age 75 (62–84), initial mKPS 80 (50–90), mPFS 16.2 m, and mOS not reached. Initial KPS and MMSE score tended to be worse in WBRT group, presumably due to enrichment of patients with poorer performance status and more comorbidities. A decline in the Fazekas score was not associated with MMSE deterioration.Conclusions: The preliminary analysis was not informative enough, and further extensive imaging analysis will be exploited.

scholarly journals Comparative DNA Flow Cytometric Study of Primary Intraocular and Central Nervous System Lymphomas

2020 ◽  
Vol 8 (2) ◽  
Author(s):  
Teresa Martinu ◽  
Claudia P. Correia ◽  
Andersson M. Figueiredo ◽  
Miguel N. Burnier Jr
Keyword(s):  
Flow Cytometry ◽  
Dna Content ◽  
Primary Cns Lymphoma ◽  
Spatial Location ◽  
Intraocular Lymphoma ◽  
Dna Flow Cytometry ◽  
Cns Lymphoma ◽  
Primary Intraocular Lymphoma ◽  
Human Tonsil ◽  
Tissue Samples

Primary intraocular lymphoma is generally considered as a subset of primary CNS lymphoma. This study attempts to show that they may in fact represent distinct entities by comparing their respective proliferation rates using DNA flow cytometry. Four samples of primary intraocular lymphoma and seven samples of primary CNS lymphoma were analyzed, all from paraffin-embedded tissue. All tumors were of the large B-cell type. A normal human tonsil sample was used as a control. Tissue samples were analyzed by DNA flow cytometry, which is a precise and objective method to measure DNA content and cell proliferation of a tumor. S-phase fraction (SPF) and DNA content were measured for each sample. The average SPF for primary intraocular lymphoma was significantly higher than that of primary CNS lymphoma, 23.8 (range: 18.9 to 29.6) versus 15.1 (range: 1.1 to 25.1) respectively. Of the 11 tumors analyzed, 2 brain tumors were aneuploid and 1 eye tumor was peridiploid. All other tumors were diploid. Thus, no significant pattern was detected in the DNA content of the tumors. This lack of clinical significance of tumor aneuploidy is consistent with data reported in the literature. The results of this study indicate that primary intraocular lymphoma is more aggressive and of higher grade than primary CNS lymphoma. The different proliferation rates of intraocular and CNS lymphomas may be explained by either their different spatial location or a distinct genetic composition, the latter reinforcing the hypothesis that the two are fundamentally different entities

NIMG-68. SARCOPENIA AS MEASURED BY TEMPORALIS MUSCLE WIDTH IS A PREDICTOR OF SURVIVAL IN PRIMARY CNS LYMPHOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi145-vi145
Author(s):  
Alipi Bonm ◽  
Anthony Menghini ◽  
Jerome Graber
Keyword(s):  
Clinical Trials ◽  
Standard Deviation ◽  
Intraclass Correlation ◽  
Primary Cns Lymphoma ◽  
Muscle Thickness ◽  
Important Variable ◽  
Cns Lymphoma ◽  
Routine Practice ◽  
Temporalis Muscle ◽  
Increased Risk

Abstract Sarcopenia refers to a loss of skeletal muscle mass, which has been associated with increased risk of injury and decreased ability to perform activities of daily living. In multiple cancers including systemic lymphomas, sarcopenia has been strongly associated with survival and may be an important way to risk stratify patients in clinical trials as well as routine practice. Temporalis muscle width has been reported as an indicator of sarcopenia and independent predictor of outcomes in multiple settings including glioblastoma, brain metastases and subarachnoid hemorrhage. We evaluated temporalis width in primary CNS lymphoma (PCNSL) patients at presentation and outcomes. Using an institutional database of immunocompetent PCNSL patients treated at the University of Washington, two independent readers reviewed the initial MRIs for 104 patients who presented from 2011-2021 and measured the width of the temporalis muscle on axial T1 images. Median duration of follow up was 42.2 months (range 0.59-125.9 months). Median age at diagnosis was 65 (range 19-90 years), and patients were 42.8% male, 57.2% female. Interrater variability was acceptable with an average intraclass correlation coefficient of 0.934. Temporalis measurements were normally distributed, with mean 0.79 cm and standard deviation 0.18 cm. We divided patients into two groups, those with temporalis width less than or greater than 1 standard deviation below the mean (absolute value 0.60 cm). Temporalis width was strongly associated with survival among all patients (χ2=15.5, p&lt; 0.001) as well as patients 65 years or older (χ2=4.5, p=0.03). We conclude that sarcopenia as measured by temporalis muscle thickness is associated with survival in PCNSL and may be an important variable to consider in clinical trials and routine practice.

Treatment of Primary CNS Lymphoma with Induction High-Dose Methotrexate, Temozolomide, Rituximab Followed by Consolidation Cytarabine/Etoposide: A Pilot Study with Biomarker Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1364-1364 ◽  
Author(s):  
Samar Issa ◽  
Arthur Shen ◽  
Jon Karch ◽  
Cigall Kadoch ◽  
Marc Shuman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Immunohistochemical Analysis ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Biomarker Analysis

Abstract Background: There is no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). The goals of this study were: to determine the safety and efficacy of a methotrexate (MTX)-based induction therapy followed by high-dose consolidation chemotherapy and the elimination or deferral of whole brain irradiation, to identify molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 23 newly diagnosed, CD20-positive, immunocompetent PCNSL patients were treated with combination high-dose intravenous MTX (8 gm/m2), temozolomide (150 mg/m2/day) and intravenous rituximab (375 mg/m2) (MTR). Patients in complete remission (CR) after eight courses of MTX were offered consolidation with high-dose cytarabine (2 g/m2 x 8 doses) and etoposide (40 mg/kg over 96 hours) (AE). Candidate markers of outcome in PCNSL were identified by gene expression profile analysis of an independent, multicenter dataset of PCNSL tumors. Immunohistochemical analysis of one of these markers, death-associated protein-1 (DAP-1), was performed on paraffin sections of tumors from 18 of the patients treated with the MTR regimen. Results: MTR induction followed by AE consolidation was well tolerated with no treatment-related mortality or evidence for neurotoxicity. Thirteen patients (56.5%) attained CR with induction; 8 received consolidation; 5 in CR refused AE. Median progression-free (PFS) and overall survival (OS) has not yet been reached with a median follow-up of 33 months. Karnovsky performance status (KPS) correlated with improved survival (p<0.0281). Expression by lymphoma cells of DAP-1, a regulator of apoptosis, was associated with improved progression-free survival (p<0.03) and overall survival (p<0.038). Conclusions: Combination MTR followed by AE is well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A multi-center study has been initiated to further evaluate this regimen. DAP-1 may be a tumor suppressor whose expression in PCNSL predicts a favorable response to MTX-based therapy.

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