scholarly journals ML-7 Liquid biopsy for MYD88 mutation in cerebrospinal fluid in patients with suspected primary CNS lymphoma

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi23-vi23
Author(s):  
Yamagishi Yuki ◽  
Nobuyoshi Sasaki ◽  
Yuko Matsushita ◽  
Saki Shimizu ◽  
Yoshie Matsumoto ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Complete Response ◽  
Digital Pcr ◽  
Cns Lymphoma ◽  
High Dose ◽  
Mr Images ◽  
Ataxic Gait ◽  
Surgical Biopsy

Abstract Background: Treatment intervention for central nervous system lymphoma (CNSL) requires pathological diagnosis by surgical biopsy. However, there are some cases in which the risk of surgery is high due to age, comorbidities, localization of lesions, etc. We are developing a CNSL diagnostic method based on the detection of MYD88 L265P mutation by digital PCR (dPCR) using CSF-DNA, and a high accuracy with a sensitivity of 92.9% and a specificity of 100% has been reported. Here, we report two cases with suspected brain stem CNSL, whose treatment strategy was determined by integrated clinico-laboratory information including neurological presentations, imaging, and the result of liquid biopsy. Result: Case 1. A 63-year-old woman visited our hospital with a complaint of right hemiplegia, which deteriorated in two months. MR images revealed a contrast-enhancing lesion in the left midbrain-ventral pons, suggesting CNSL. Biopsy was not considered because of its location, while dPCR using CSF-DNA showed a cluster of MYD88 mutation signals. Based on these work-ups, she was treated with high-dose methotrexate-based chemotherapy, resulting in a complete response with marked improvement of symptoms. Case 2. An 83-year-old man was referred for a history of diplopia and ataxic gait lasting for a month. MR images revealed an invasive lesion on his right midbrain-dorsal pons. Biopsy was declined due to the location, and liquid biopsy using CSF-DNA was performed to assist the diagnosis. In the first test, the CSF-DNA yield was too insufficient to determine the mutation signal by dPCR. The second dPCR using sufficient amount of CSF-DNA resulted in the Target/Total value of 0.049% which was lower than the threshold, suggesting the absence of MYD88 mutation. The patient underwent radiation therapy accordingly.Conclusions: CSF MYD88 mutation analysis by dPCR may have clinical utility and requires sufficient amount of CSF-DNA for exclusion of noise signals.

scholarly journals High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junyao Yu ◽  
Huaping Du ◽  
Xueshi Ye ◽  
Lifei Zhang ◽  
Haowen Xiao
Keyword(s):  
Meta Analysis ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Dose Methotrexate

AbstractWith the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

scholarly journals P14.113 The role of maintenance high-dose methotrexate chemotherapy in elderly primary CNS lymphoma patients with complete response to induction immunochemotherapy

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii95-iii95
Author(s):  
K Mishima ◽  
M Shirahata ◽  
J Adachi ◽  
T Suzuki ◽  
T Fujimaki ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Maintenance Treatment ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Complete Response ◽  
The Elderly ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Abstract BACKGROUND The addition of high-dose methotrexate (HD-MTX)-based chemotherapy to whole brain irradiation (WBRT) has improved the prognosis of primary central nervous system lymphoma (PCNSL). However, the high neurotoxicity rates observed, especially in the elderly, raised interest in chemotherapy-only treatments. Withholding radiotherapy substantially decreases the risk of neurotoxicity, however, disease control may be compromised. Therefore, developing a novel treatment for the elderly PCNSL patients (ePCNSL) is crucial. In the elderly who cannot tolerate WBRT as a consolidation, maintenance treatment may serve as a feasible approach after an initial response. We treated ePCNSL with induction immunochemotherapy with rituximab (RIT) and HD-MTX, maintenance chemotherapy with HD-MTX and deferred WBRT. Here, we retrospectively investigated the prognosis for ePCNSL that became CR after the induction chemotherapy. MATERIAL AND METHODS Newly diagnosed ePCNSL (median age: 74 years) received biweekly RIT/ HD-MTX (375 mg/m2/dose; 3.5g/m2/dose) for 6 cycles (induction) followed by monthly RIT/MTX for 2 cycles (consolidation) and then were treated differently according to the radiological response. With CR patients, HD-MTX was continued with every 3 months (maintenance) for 2 years. Patients who did not obtain consent for maintenance therapy were followed up. RESULTS Of the 42 ePCNSL (median age 74 years), 26 had CR after induction and consolidation, of which 18 cases were carried out maintenance (M +) and 8 cases were followed up (M-). The median age was 74 and 76, respectively. Median progression-free survival (mPFS) was 73 months in the M+ group and 24.6 months in the M- group. Median overall survival (mOS) is 92.5 months versus 27.6 months, respectively. Both mPFS (P= 0.025) and mOS (P =0.0003) were significantly prolonged by maintenance therapy. In addition, ePCNSL with tumors involvement of deep brain structure had a poor prognosis. CONCLUSION It was suggested that maintenance treatment with HD-MTX may improve the prognosis for ePCNSL that reached complete response after induction therapy.

First Results of the Acsé Pembrolizumab Phase II in the Primary CNS Lymphoma (PCNSL) Cohort

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Khe Hoang-Xuan ◽  
Roch Houot ◽  
Carole Soussain ◽  
Marie Blonski ◽  
Anna Schmitt ◽  
...  
Keyword(s):  
Objective Response ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Moderate Activity ◽  
Multicentric Study ◽  
First Results ◽  
Duration Of Response

Background: AcSé Pembrolizumab is a Phase 2, open-label, single-arm, multi-cohort, multicentric study investigating the efficacy and safety of pembrolizumab monotherapy in patients with advanced rare cancers (NCT03012620). Here, we report the first results of Pembrolizumab in the cohort of Primary Central Nervous System Lymphoma (PCNSL). Methods: Main inclusion criteria were: relapsed or refractory PCNSL after one or several lines of treatment including high dose Methotrexate based chemotherapy, pathologically confirmed diffuse large B cell lymphoma, age>18, HIV negative, concurrent steroid medication at a dose no greater than prednisone 20 mg/day or equivalent. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycles for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to IPCG at 84 day after the start of treatment. Secondary endpoints included best response (ORR), duration of response, progression-free survival (PFS), overall survival (OS), and safety. Analysis used all enrolled patients. Results: 50 patients suffering from PCNSL, including 9 primary vitreoretinal lymphoma (PVRL) were included from July, 2017 to October, 2019. Median age was 72 years (range: 43 to 83), Median PS (ECOG) was 1 (range 0-1). The median number of cycles was 4 (range 1-35). At 84 days from start of treatment, 6 patients responded (4 CR+2PR). Overall, 3 patients whose response was not assessed were considered as failures, and the rates of ORR (CR+PR), stable disease (SD), progressive disease (PD) were 26% (13/50, 8 CR + 5 PR), 10% (5/50), 58% (29/50), respectively. ORR was 29% (12/41) and 11% (1/9) in primary cerebral lymphoma and PVRL respectively. After a median follow-up of 6.7 months (range 0.2-27.4), median PFS was 2.6 months, with 6-month PFS of 29.8% and 6-month OS of 60.4%. In responders, median duration of response was estimated at 10 months (95%CI, 2.7 to 12.5). Grade III and IV toxicities related to the drug were observed in 4 patients (8%) and one patient (2%) respectively. No related toxic death was reported. Conclusion: Pembrolizumab shows moderate activity in relapsed/ refractory PCNSL with acceptable toxicity, supporting further studies evaluating its use in combination therapies. Disclosures Hoang-Xuan: BTG: Consultancy, Research Funding. Houot:Bristol-Myers Squibb: Honoraria; MSD: Honoraria; Gilead: Honoraria; Kite: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Schmitt:Celgene: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen: Honoraria. Ahle:Roche: Honoraria; Novartis: Honoraria; Biogene: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria. Bories:Abbvie: Consultancy; Celgen: Consultancy; Gilead: Consultancy; BMS: Honoraria; Novartis: Honoraria. Houillier:BTG: Consultancy.

scholarly journals PC3 - 130 A Meta-Analysis on the use of High-Dose Methotrexate Only Versus Combination Chemotherapy for the Treatment of Newly-Diagnosed Patients with Primary CNS Lymphoma

2016 ◽  
Vol 43 (S4) ◽  
pp. S20-S21
Author(s):  
M.C. Concepcion Sales
Keyword(s):  
Side Effects ◽  
Disease Progression ◽  
Combination Chemotherapy ◽  
Primary Cns Lymphoma ◽  
Complete Response ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cochrane Central Register ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Primary CNS Lymphoma (PCNSL) is an unusual extranodal form of Non-Hodgkin’s Lymphoma with a locally aggressive course but a rare tendency to disseminate systemically. There are various modalities available for the treatment of PCNSL which include chemotherapy, radiotherapy, surgery and immunotherapy. The effectiveness of adding another anti-neoplastic agent to HD-MTX have been optimized in small scale studies yet the “ perfect combination” has yet to be elucidated Objectives: This study aims to 1) compare the response to treatment of monotherapy with high-dose Methotrexate (HD-MTX) versus HD-MTX and an additional anti-neoplastic agent by evaluating complete response, partial response, stable disease and disease progression and 2) to compare the hematologic and non-hematologic side effects among patients subjected to monotherapy vs combination chemotherapy. Methodology: Journals from Medline, EMBASE, Cochrane Central Register of Control Trials (CENTRAL) and other relevant websites (www.clinicaltrials.org) without any restrictions in the year, language and status of publication were searched. Literatures cited by eligible studies and systemic reviews were also checked to identify useful articles. The following Medical Subject Headings (MeSH) were used: ‘primary CNS lymphoma’, ‘treatment’, ‘chemotherapy’ and ‘randomized control trial’. Statistical analysis was performed using the RevMan software version 5.1. Odds ratio (OR) and 95 % confidence interval (95% CI) were used as summary statistics. Results and Conclusion: The use of high-dose methotrexate and another anti-neoplastic agent showed benefit in terms of achieving complete response and delaying disease progression among patients diagnosed with PCNSL. However, the risks of hematologic toxicities such as anemia, neutropenia, thrombocytopenia and infection was higher in patients treated with the combination chemotherapy. Significant non-hematologic side effects such as mucositis was also observed in patients receiving an add-on to high dose methotrexate.

Treatment outcomes of patients with primary central nervous system lymphoma: Single center experience from south India.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13010-e13010
Author(s):  
Krishna Mohan V T Mallavarapu ◽  
Santa Ayyagari ◽  
Senthil Jagannathan Rajappa ◽  
Krishnam Raju Alluri ◽  
Sudha Murthy S
Keyword(s):  
Overall Survival ◽  
Treatment Outcomes ◽  
Treatment Protocol ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Single Center Experience ◽  
Dose Methotrexate

e13010 Background: Primary CNS Lymphoma (PCNSL) is a rare neoplasm of the brain accounting for 1-2% of all brain tumours. Incidence and histopathologic features of PCNSL in India has been reported; however, reports on therapy outcomes of the disease are lacking. We report treatment outcomes of patients with PCNSL at our institute. Methods: Case records of all patients treated for PCNSL between 2008 and 2012 were retrospectively analysed. Epidemiologic details, treatments given, progression free and overall survival were calculated. Patients who completed at least high dose methotrexate (1.5 gram/ m2) for 5 courses with or without RT were included for analysis. Overall survival (OS) was defined as time from diagnosis till death/lost to follow up. Results: A total of seventeen patients were analysed. The median age at diagnosis was 58 years and M: F ratio was 1.14:1. Thirteen out of seventeen patients were eligible for analysis; six could complete the total treatment protocol which included methotrexate, vincristine, procarbazine, Dexamethasone, Radiation therapy followed by high dose cytarabine. Median overall survival was 20 months (range 2-54 months). Among those who completed the protocol, median survival at 21 months was not reached with 66% survival. Conclusions: Treatment of PCNSL with at least high dose methotrexate with or without whole brain radiation offers moderate results. Completion of treatment protocol is associated with better overall survival.

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.

Early Relapses in Primary CNS Lymphoma (PCNSL) without Intraventricular Treatment.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4440-4440
Author(s):  
Ingo G.H. Schmidt-Wolf ◽  
Hendrick Pels ◽  
Annika Jurgens ◽  
Axel Glasmacher ◽  
Holger Schulz ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Response Duration ◽  
Complete Response ◽  
High Response Rate ◽  
High Rate ◽  
Cns Lymphoma ◽  
High Dose ◽  
Median Response ◽  
Kaplan Meier ◽  
Intraventricular Treatment

Abstract Background: A systemic and intraventricular polychemotherapy regimen (“Bonn protocol”) with deferred radiotherapy had resulted in durable responses in 75% of patients < 60 years with primary CNS lymphoma (PCNSL), but had been complicated by a high rate of Ommaya reservoir infections. Purpose: Here, efficacy and toxicity of this regimen but without intraventricular treatment was evaluated in PCNSL. Patients and Methods : From 08/03 to 11/05, 18 patients with PCNSL < 60 years (median age 53 years) were treated within a phase II trial with a high-dose methotrexate (MTX; cycles 1,2,4 and 5) and cytarabine (Ara-C; cycles 3 and 6) based systemic therapy including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide. Results: Study accrual was prematurely stopped in 11/05 due to a high rate of early relapses. Seventeen/18 patients were assessable for response: Nine (53%) achieved complete response (CR), two (12%) complete response/unconfirmed (CRu), two (12%) partial response (PR), four (24%) showed progressive disease (PD); in one treatment was stopped due to toxicity. Median follow-up is 23 months; Kaplan-Meier estimates for median response duration were ten months only in responding patients and for median time to treatment failure (TTF) eight months in the whole group; median overall survival (OS) has not yet been reached. Systemic toxicity was mainly hematologic. Conclusions: In patients < 60 years with PCNSL polychemotherapy without intraventricular treatment results in a high response rate, but is associated with early relapses in the majority of cases. This is in contrast to the results achieved with the same protocol but with inclusion of intraventricular treatment.

Primary CNS Lymphoma in a HIV Negative Population: A Review of Clinicopathologic Characteristics, Therapy, and Outcomes of 59 Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4858-4858
Author(s):  
Michael V. Jaglal ◽  
Bijal D. Shah ◽  
Jennifer L. Cultrera ◽  
Eduardo M. Sotomayor ◽  
Michael B Tomblyn ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Clinicopathologic Characteristics ◽  
Female Ratio ◽  
Common Location ◽  
Chi Square Analysis

Abstract Abstract 4858 Background Primary central nervous system lymphoma (PCNSL) is a rare aggressive variant of diffuse large B cell lymphoma (DLBCL) with a poor prognosis. Optimal therapeutic strategies have not been defined yet in primary CNS lymphoma. High dose Methotrexate (HD MTX) is an effective chemotherapeutic agent with superior outcomes compared to historical studies using whole brain radiation therapy (WBRT). The combination of HD MTX with WBRT showed improved response rates compared to chemotherapy (CT) alone, but was associated with greater risk of neurotoxicity in patients >60 years old. Purpose To review clinicopathologic characteristics, therapy and outcomes of 59 patients with primary CNS DLBCL without HIV. Methods This was a single center retrospective review of pts with confirmed diagnosis of primary CNS DLBCL from 1999 to 2012. Data was extracted from the Moffitt Cancer Center (MCC) electronic records. Baseline demographics, clinical, pathological and treatment data were collected and analyzed. Patients were stratified according to their treatment regimens including HD MTX (3g/m2) alone or in combinations and WBRT alone or in combination with CT. Descriptive statistical analyses were utilized. Chi square analysis and t- test were performed to compare categorical and continuous variables. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data was analyzed using SPSS version 19.0 statistical software. Results 59 patients who underwent CT and/or WBRT for PCNSL between 1999 and 2012 were identified. The age range at diagnosis was 17–85 years with median age of 64. 35 of 59 patients (59%) were ≥ 60 years old. Male to female ratio was 1.27:1 (33:26). The median ECOG PS was 1. A majority of patients presented with motor deficits, 29 out of 59. The most common location of lymphoma was in the cerebral hemispheres. The median survival of the entire cohort was 37 months. 18 of 59 pts (25%) survived ≥ 60 months. In the cohort of pts that survived ≥ 60 months, a majority 16 of 18 (89%) received HD MTX. Patients treated with initial WBRT and chemotherapy revealed inferior overall survival (OS) compare to patients treated with induction chemotherapy alone (OS 37 months vs. 66 months) (p=0.011). Patients over the age of 60 had worse outcomes compared to patients who were less than the age of 60 (OS 33 months versus 70 months) (p=0.023). Conclusions HD MTX was the most frequently utilized CT regimen in the cohort of patients surviving > 60 months. Administering WBRT combined with chemotherapy was associated with worse outcomes in this retrospective analysis. Patients with primary CNS lymphoma who are older than 60 have worse outcomes in this retrospective analysis compared to patients younger than 60. Disclosures: Sokol: Celgene: Honoraria, Speakers Bureau.

Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.

1998 ◽  
Vol 16 (9) ◽  
pp. 3000-3006 ◽  
Author(s):  
V Sandor ◽  
V Stark-Vancs ◽  
D Pearson ◽  
R Nussenblat ◽  
S M Whitcup ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Response Rate ◽  
Survival Rates ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Intraocular Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Free Survival

PURPOSE Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.

Sign in / Sign up

Export Citation Format

Share Document