High-dose methotrexate for elderly patients with primary CNS lymphoma

The introduction of methotrexate (MTX)-based chemotherapy has improved median survival for patients with primary CNS lymphoma (PCNSL). Older age is a negative prognostic marker in patients with PCNSL and may increase the likelihood of MTX toxicity. We studied the response and adverse effects of intravenous high-dose MTX in patients who were 70 or more years of age at the time of diagnosis. We identified 31 patients at our institution diagnosed with PCNSL at age > or =70 years (median, 74 years) who were treated with high-dose MTX (3.5-8 g/m(2)) as initial therapy from 1992 through 2006. The best response to MTX was determined by contrast-enhanced MRI. Toxicity was analyzed by chart review. These 31 patients received a total of 303 cycles of MTX (median, eight cycles per patient). Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. In 30 evaluable patients, the overall radiographic response rate was 96.7%, with 18 complete responses (60%) and 11 partial responses (36.7%). Progression-free survival and overall survival were 7.1 months and 37 months, respectively. Grade I-IV toxicities were observed in 27 of 31 patients and included gastrointestinal disturbances in 58% (3.2% grade III), hematological complications in 80.6% (6.5% grade III), and renal toxicity in 29% (0% grade III/IV). High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL.     

Long-term Remission of Primary Central Nervous System Lymphoma by Intensified Methotrexate Chemotherapy

High-dose (1–3.5g/m²) methotrexate (MTX) followed by whole-brain radiation therapy (WBRT) has consistently improved length of survival in primary central nervous system lymphoma (PCNSL), but the prognosis remains dismal. To optimize and enhance the dose intensity of MTX, we applied MTX at 8g/m² to 20 patients with PCNSL. In an effort to lower the risk of neurotoxic treatment sequelae, the WBRT dose was reduced to 30Gy in cases of complete remission after MTX therapy. Further, omission of WBRT and administration of stereotactic radiotherapy (SRT) were undertaken in 3 older patients. The overall response rate to the MTX therapy was 83%. The median progression free survival (PFS) was 54 months with a median overall survival (OS) of 57 months. Achieving a complete response after MTX therapy was significantly associated with a longer PFS. Late neurotoxicity was encountered in 4 (50%) of 8 patients who were aged 60 years or older and received WBRT, but in none of 12 patients who were aged less than 60 years or avoided WBRT. All older patients who underwent SRT sustained complete remission without a dementing disease. Intensifying the MTX dosage to 8g/m² appears more promising in comparison to results reported with MTX doses of 1–3.5g/m². In younger patients, the establishment of complete remission by intensified MTX therapy and subsequent WBRT with a relatively lower dose could promise durable tumor remission with an acceptable neurotoxicity. In older patients, WBRT should be avoided to sustain a meaningful survival, and SRT may provide a valid strategy in terms of enhancing local disease control without undue risk.     

AIDS-related Central Nervous System Lymphomas

Purpose: To evaluate combined radio-chemotherapy in patients with AIDS-related lymphomatous meningitis (LM) or primary central nervous system lymphoma (PCNSL).Patients and methods: Eighteen men and 2 women with AIDS had cytologically documented LM. Fifteen patients had systemic non-Hodgkin's lymphoma with LM and 5 patients had PCNSL with CSF dissemination. Standardized pre-treatment evaluations included contrast cranial MRI, placement of an intraventricular reservoir, contrast spine MRI, ophthalmologic evaluation and ¹¹¹Indium-DTPA CSF flow studies. Regions of bulky or symptomatic disease were treated with limited-field irradiation. Concurrent systemic chemotherapy was administered in 18 patients. All patients were scheduled to receive intraventricular methotrexate (MTX) according to a concentration×time (C×T) drug schedule. In cytologic or clinical failures, patients were treated with salvage therapy using intraventricular ara-C and in a similar manner, patients were treated with intraventricular thio-TEPA following cytologic relapse or clinical failure intraventricular following intraventricular ara-C.Sixty-seven patients (63 men; 4 women) with PCNSL underwent a standardized pre-treatment evaluation as in patients with LM and were treated according to 3 schedules. In the first group (n=15), comfort care was offered. In the second group (n=45), whole brain radiotherapy was administered. In the third group (n=7), patients were treated with combined radio- and chemotherapy using systemic procarbazine, CCNU and vincristine (PCV-3). The third group was selected based on a Karnofsky performance status 60, no evidence of disseminated PCNSL, a CD4 count 200, no concurrent opportunistic infection and a patient's desire for aggressive therapy.Results: In the LM patient group, 16 patients were evaluable as 4 patients subsequently withdrew consent for treatment. Median time to tumor progression/survival were as follows: not-treated (n=4) 12 days/1 month; treated non-responding (n=6) 30 days/2 months; and treated responding (n=10) 130 days/6 months. In the PCNSL patient group, median range survival were as follows: comfort care (n=15) 1.5/0.5–3 months; whole brain radiotherapy (n=45) 4/1.5–5 months; and combined radio-chemotherapy (n=7) 13/10–18 months.Conclusions: Combined radio- and chemotherapy is appropriate for a small subset of patients with AIDS and either LM or PCNSL. This approach results in meaningful palliation not strikingly dissimilar from that seen in non-AIDS patients.     

Analysis of Key Factors Associated with Response to Salvage High-Dose Methotrexate Rechallenge in Primary Central Nervous System Lymphoma with First Relapse

Background: Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin’s lymphoma that occurs in the central nervous system. Although sensitive to chemotherapy, 35–60% of PCNSL patients still relapse within 2 years after the initial treatment. High-dose methotrexate (HD-MTX) rechallenge is generally used in recurrent PCNSL, especially for patients who have achieved a response after initial methotrexate (MTX) treatment. However, the overall remission rate (ORR) of HD-MTX rechallenge is about 70–80%. Additionally, the side effects of HD-MTX treatment endanger the health of patients and affect their quality of life. Methods: This is a retrospective study of patients with first relapse PCNSL at Huashan Hospital, Fudan University between January 2000 and November 2020. By comparing the clinical characteristics and radiological manifestations of first relapsed PCNSL patients with remission and non-remission after receiving HD-MTX rechallenge, we screened out the key factors associated with HD-MTX rechallenge treatment response, to provide some help for the selection of salvage treatment strategies for patients with recurrent PCNSL. Additionally, patients with remission after HD-MTX rechallenge were followed up to identify the factors related to progression-free survival of the second time (PFS2) (time from the first relapse to second relapse/last follow-up). The Kruskal–Wallis and Pearson chi-square tests were performed to examine the univariate association. Further, multivariable logistic regression analysis was used to study the simultaneous effect of different variables. Results: A total of 207 patients were enrolled in the study based on the inclusion criteria, including 114 patients in the remission group (RG) and 81 patients in the non-remission group (nRG), and 12 patients were judged as having a stable disease. In Kruskal–Wallis and Pearson chi-square tests, progression-free survival rates for first time (PFS1) and whether the initial treatment was combined with consolidated whole brain radiotherapy (WBRT) were related to the response to HD-MTX rechallenge treatment, which was further validated in regression analysis. Further, after univariate analysis and regression analysis, KPS was related to PFS2. Conclusions: For PCNSL patients in their first relapse, HD-MTX rechallenge may be an effective salvage treatment. PFS1 and whether initial treatment was combined with consolidation WBRT were associated with HD-MTX rechallenge treatment response. In addition, patients with higher KPS at the time of the first relapse had a longer PFS2 after HD-MTX rechallenge treatment.     

Clinical Outcomes of RTOG 9310 Protocol for Primary Central Nervous System Lymphoma: Single-Center Experience with 87 Patients

The Radiation Therapy Oncology Group (RTOG) 9310 protocol clinical trial established high-dose methotrexate (HDMTX) as the standard for primary central nervous system lymphoma (PCNSL). We aimed to investigate the RTOG 9310 protocol’s PCNSL outcomes by examining progression-free survival (PFS) and overall survival (OS) rates and determining the influential factors. Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL and treated with the RTOG 9310 protocol. All received HDMTX 2.5 g/m² and vincristine 1.4 mg/m²/day for 1 day during weeks 1, 3, 5, 7, and 9, and procarbazine 100 mg/m²/day for 1 day during weeks 1, 5, and 9. Dexamethasone was administered on a standard tapering schedule from the first week to the sixth week. Whole brain radiotherapy (WBRT), consisting of 45 Gy for patients with less than a complete response to the chemotherapy or 36 Gy for complete responders, was started 1 week after the last dose of chemotherapy was administered. Within three weeks of the completion of WBRT, patients received two courses of cytarabine, which were separated by 3–4 weeks. Clinical, radiological, and histopathological characteristics were retrospectively reviewed. All patients completed five HDMTX cycles and a mean follow-up of 60.2 (range, 6–150) months. Twenty-eight (32.2%) patients experienced recurrence during follow-up. The mean time to recurrence was 21.8 months, while the mean PFS was 104.3 (95% confidence interval (CI), 90.6–118.0) months. Eleven (12.6%) patients died; the mean OS was 132.1 (95% CI, 122.2–141.9) months. The 3- and 5-year survival rates were 92.0% and 87.4%, respectively. One patient experienced acute renal failure, while the remainder tolerated any cytotoxic side effects. On multivariate analysis, the Eastern Cooperative Oncology Group performance score ≤ 2; the International Extranodal Lymphoma Study Group low-risk status; XBP-1, p53, and c-Myc negativity; homogenous enhancement; gross total resection, independently correlated with long PFS and OS. The RTOG 9310 protocol is effective for PCNSL and features good outcomes.     

Primary Central Nervous System Lymphomas Express Vh Genes with Intermediate to High Somatic Mutations

Primary central nervous system lymphoma (PCNSL) is a rare disease, especially among non-AIDS patients. Although almost all PCNSLs belong to the diffuse large B-cell lymphoma (DLBL) category, its clinical course differs from that of other types of DLBL. To elucidate the histogenesis of PCNSL, we analyzed the source of the cells from its variable region (VH) sequences using the polymerase chain reaction (PCR) method to amplify the immunoglobulin heavy chain (IgH) gene of DNA extracted from paraffin sections. Fifteen patients with AIDS-unrelated PCNSL of DLBL type, (7 males and 8 females), were evaluated. Only one case showed positive evidence of EBV infection. The prognosis was very poor with a median survival of 9 months. Analysis of the VH sequences revealed that the VH4 family was used in 4 cases and the VH3 family in 2 cases. The homology with previously published germline sequences was random, ranging from 82.7-93.2%, showing intermediate to high somatic mutations. In 3 of 6 cases, the existence of intraclonal diversity was suspected. These findings suggest that PCNSLs are histogenetically derived from antigen selected B cells in the germinal center (GC) environment.     

Primary intraocular lymphoma: an International Primary Central Nervous System Lymphoma Collaborative Group Report.

BACKGROUND: Primary intraocular lymphoma (PIOL) is an uncommon subset of primary central nervous system lymphoma. Because it is rare and difficult to diagnose, the natural history and optimal management are unknown. PATIENTS AND METHODS: A retrospective study of 83 HIV negative, immunocompetent PIOL patients was assembled from 16 centers in seven countries. RESULTS: Median age at diagnosis was 65. Median ECOG performance status was 0. Presenting symptoms included blurred vision, decreased visual acuity, and floaters. Median time to diagnosis was 6 months. Diagnosis was made by vitrectomy (74), choroidal/retinal biopsy (6) and ophthalmic exam (3). Eleven percent had positive CSF cytology. Initial treatment was categorized as focal in 23 (intra-ocular methotrexate, ocular radiotherapy) or extensive in 53 (systemic chemotherapy, whole brain radiotherapy). Six received none; details are unknown in one. Forty-seven relapsed: brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Median time to relapse was 19 months. Focal therapy alone did not increase risk of brain relapse. Median progression free (PFS) and overall survival (OS) were 29.6 and 58 months, respectively, and unaffected by treatment type. CONCLUSION: Treatment type did not affect relapse pattern, median PFS or OS. Focal therapy may minimize treatment toxicity without compromising disease control.     

Ongoing Protocols for Non-AIDS Primary Central Nervous System Lymphoma

The optimal treatment for primary central nervous system lymphoma (PCNSL) remains undefined. In this paper, we review the main multi-institutional ongoing protocols for PCNSL. Most of the current protocols evaluate the efficacy of combination high-dose methotrexate-based chemotherapy and brain irradiation in phase II studies. Some trials focus on chemotherapy alone as initial treatment, in order to minimize long-term cognitive sequellae. Because old age appears as a major predisposing factor for combined RT and CT neurotoxicity some specific protocols have been proposed to this particular population.     

CEOP方案联合大剂量甲氨喋呤治疗有中枢复发倾向的侵袭性淋巴瘤

目的探讨CEOP方案联合大剂量甲氨喋呤治疗有中枢复发倾向的侵袭性淋巴瘤的临床疗效。方法7例有中枢复发倾向的侵袭性淋巴瘤均接受CEOP方案联合大剂量甲氨喋呤(3.0 g·m-2,静脉滴注6h,第10天)化疗。结果 7例患者中,6例可评价疗效,均达到完全缓解。主要毒副反应为骨髓抑制(其中Ⅲ、Ⅳ度粒细胞减少发生率为41%)和谷丙转氨酶升高(44%),非血液学毒性少而轻,6疗程因粒细胞减少甲氨蝶呤给药延迟至第15天,无治疗相关性死亡发生。结论 CEOP方案联合大剂量甲氨喋呤治疗侵袭性淋巴瘤近期疗效较好,可作为有中枢复发倾向的侵袭性淋巴瘤的治疗方案,治疗过程中应当注意骨髓抑制和谷丙转氨酶升高的防治。     

Systemic Chemotherapy with Vincristine,Cyclophosphamide, Doxorubicin and Prednisolone Following Radiotherapy for Primary Central Nervous System Lymphoma: A Phase II Study

We treated 23 patients with primary central nervous system lymphoma with a protocol of conventional radiation up to 55±5Gy followed by 4 to 6 cycles of intravenous doxorubicin (30mg/m2), vincristine (1mg/m2) and cyclophosphamide (350mg/m2), and oral prednisolone (8–30mg/m2) (VEPA chemotherapy) repeated at 2-week intervals. The median age of the 23 patients was 59 years, and the median World Health Organization performance status score was 2. Seventeen patients received 4 or more courses of the chemotherapy, but 6 received only 1 or 2 courses for various reasons. The median survival time for all 23 patients was 25.5 months and their 5-year survival rate was 23%. These values were 34 months and 32%, respectively, for the 17 patients who received 4–6 courses of chemotherapy. After treatment, decline in performance status unaccompanied with tumor recurrence was observed in 44% of the patients; the incidence was apparently higher in older than in younger patients. The survival results obtained with this combined radiochemotherapy regimen appear to be better than those reported in most previous studies of patients treated with radiation alone. Post-irradiation VEPA chemotherapy appears to be worthy of further evaluation.     

High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma

We conducted a prospective Phase II study of high-dose methotrexate (HD-MTX) and rituximab with deferred whole brain radiotherapy in patients with newly diagnosed B-cell primary central nervous system lymphoma with a primary objective of evaluating progression-free survival (PFS). Forty patients (25 men; 15 women), ages 18–93 years (median 61.5), were treated. All patients received biweekly HD-MTX/rituximab (8 g/m²/dose; 375 mg/m²/dose) for 4–6 cycles (induction) and following best radiographic response, with every 4 weeks HD-MTX (8 g/m²/dose) for 4 cycles (maintenance). Neurological and neuroradiographic evaluation were performed every 4 weeks during induction therapy and every 8 weeks during maintenance therapy. All patients were evaluable. A total of 303 cycles of HD-MTX (median 8 cycles; range 4–10) was administered. HD-MTX/rituximab-related toxicity included 16 grade 3 adverse events in 13 patients (32.5%). Following induction, 8 patients (20%) demonstrated progressive disease and discontinued therapy; 32 patients (80%) demonstrated a partial (8/40; 20%) or complete (24/40; 60%) radiographic response. At the conclusion of maintenance therapy (6–10 months of total therapy), 28 patients (70%) demonstrated either a partial (1/28) or complete (27/28) response. Overall, survival of these 28 patients ranged from 11 to 80 months (median 33.5). Survival in the entire cohort ranged from 6 to 80 months with an estimated median of 29 months. Overall, PFS ranged from 2 to 80 months (median 21.0). HD-MTX/rituximab and deferred radiotherapy demonstrated similar or better efficacy similar to other HD-MTX-only regimens and reduced time on therapy on average to 6 months.     

Primary CNS Lymphoma: Treatment with Combined Chemotherapy and Radiotherapy

Primary central nervous system lymphoma (PCNSL) is a relatively uncommon primary brain tumor, but it has become the focus of many clinical trials because of its rising incidence and unique sensitivity to systemic chemotherapeutic agents. Radiotherapy can achieve high response rates and remissions in most patients, but survival is usually only 12–18 months because disease recurs. The addition of systemic chemotherapy, particularly intravenous methotrexate, had markedly improved disease control and many patients can achieve a durable remission and occasionally cure of their disease. Conventional systemic lymphoma drug combinations such as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are ineffective. High-dose methotrexate is the single most active and important agent in the treatment of this disease. Whether improved disease control can be accomplished by adding other drugs to high-dose methotrexate or whether it is sufficient as a single agent has yet to be answered. High-dose methotrexate combined with cranial irradiation yields a median survival of at least 40 months and five year survival rates of 22%. However, neurotoxicity is substantial in a significant proportion of patients, particularly those over the age of 60 at the time of treatment. As many as 50% of such patients develop severe dementia. This is particularly important in a disease where approximately half of patients above the age of 60 had presentation. Efforts are now being directed towards not only improving disease control but also minimizing late neurotoxicity. Most efforts are currently directed towards using chemotherapy as the sole modality in the treatment of PCNSL, but both an optimal chemotherapy regimen, and the role of radiotherapy remain to be determined.     

大剂量甲氨喋呤联合消瘤芥治疗复发难治性恶性淋巴瘤12例临床观察

目的观察大剂量甲氨喋呤(MTX)联合消瘤芥(AT-1258)治疗复发难治性恶性淋巴瘤的效果及毒副反应。方法观察12例复发难治性淋巴瘤患者,给予MTX 2~3 g/m2联合AT-1258 20~40 mg化疗,同时给予水化、碱化、利尿、保肝及营养支持治疗。结果4例霍奇金淋巴瘤近期有效率为75%,8例非霍奇金淋巴瘤近期有效率为62.5%,总有效率为66.7%,未发生严重的毒副反应。结论大剂量甲氨喋呤联合消瘤芥治疗复发难治性恶性淋巴瘤是一种安全有效的方案。     

Clinicopathological Features, Survival And Prognostic Factors Of Primary Central Nervous System Lymphomas: Trends in Incidence of Primary Central Nervous System Lymphomas and Primary Malignant Brain Tumors in A Well-Defined Geographical Area; Population-Based Data from the Danish Lymphoma Registry, Lyfo, And the Danish Cancer Reistry

It has been claimed that Primary Central Nervous System Lymphoma! (PCNSL), a rare neoplasm accounting for only a small fraction of malignant brain tumors and extrancdal non-Hcdgkin lymphomas (NHL), occur with increasing frequency in immunologically normal as well as in immunocompromised individuals. In an attempt to characterize the clinicopathological features, outcome and prognostic factors of PCNSL we here report our experience in a large unselected series of patients from a well-defined region. In addition, we present data on trends in incidence of PCNSL and primary malignant brain tumors in a well-defined geographical area. In a Danish population-based NHL registry (LYFO) representing a population of 2.7 million all new cases of NHL were registered during the approximate I I-year period from 1st January 1983 to 3 1st May 1994. Incidence data of primary malignant tumors of the brain and central nervous system in western Denmark for the period 1971-1990 have been obtained from the Danish Cancer Registry. During the approximate I I-year period 3 124 new cases of NHL were registered. Of these, I 152 (37%) were extranodal and 48 were non-AIDS related PCNSL accounting for4.2% ofextranodal NHL and 1.5% of all NHL, respectively. The average annual incidence rate of non-AIDS related PCNSL during the period was I .56 cases per million population (age range: 15-85 yrs, median: 62 yrs, MIF ratio: I).In a 23-year period there was no trend towards an increasing incidence of non-AIDS related PCNSL in a well-defined population. PCNSL accounted for 1.7% of all primary malignant brain tumors. Incidence of primary malignant brain tumors was stable, except for age ranges over 70 years. However, diagnostic artifacts might be responsible for this apparent increase. Histologically, 85% were high grade. Using the Kiel classification centroblastic diffuse (60%) and immunoblastic lymphoma (13%) were the most common subtypes. Forty-three patients had 6-cell lymphoma and no T-cell lymphoma was detected. Forty-seven cases were diagnosed pre mortem. Treatment included surgical resection (26 patients), whole brain irradiation (WBRT) (43 patients) and chemotherapy (28 patients). Median survival for those receiving either WBRT or WkRT and chemotherapy was 8 months and 20 months, respectively (p = 0.78). Overall survival was 53%. 38% and 26% at I, 2 and 5 years. Cox-regression analysis identified only one factor having independent impact on survival in PCNSL performance score 2 2 (pc 0.001. RR = 5.8     

Secondary Analysis of Radiation Therapy Oncology Group study (RTOG) 9310: An Intergroup Phase II Combined Modality Treatment of Primary Central Nervous System Lymphoma

Summary Purpose: To determine whether a lower dose of hyperfractionated whole brain radiation reduces central nervous system morbidity without compromising survival for primary CNS lymphoma (PCNSL) patients receiving combined modality treatment. Materials and Methods: One hundred and two patients received a course of pre-radiation chemotherapy, followed by whole brain radiation, followed by cytosine-arabinoside. Initial radiation dose was 45 Gy/25 fractions (RT) then the study was amended to reduce this dose for complete responders to induction chemotherapy to 36 Gy/30 fractions/3 weeks (HFX). Eighty-two patients received radiotherapy and were evaluable for toxicity analysis (66 RT patients and 16 HFX patients). MMSE scores and survival for the 40 patients who received radiotherapy after complete response to chemotherapy (27 RT and 13 HFX) were compared. There were no notable differences in pre-treatment patient characteristics between the RT and HFX groups. Results: Neurotoxicity: By 4 years, there were 8/82 (10%) grade 5 neurotoxicities which included 2/16 (13%) grade 5 encephalopathies and 0/27 in the RT group of complete responders to chemotherapy. Survival: There was no statistically significant difference in overall or progression-free survival (PFS) between the chemotherapy-complete responders who received RT and HFX. Cognitive function testing: MMSE scores improved at 8 months across both treatment groups. Analysis of the area under the MMSE curve at 8 months showed no statistically significant difference between RT and HFX groups (P=0.81). Leukoencephalopathy occurred later in the HFX group than in the RT patients. Conclusion: Although the HFX schedule represented a 25% reduction in biologically effective tumor dose in comparison, PFS and overall survival were not significantly affected. The HFX regimen delayed but did not eliminate severe neurotoxicity from chemoradiation in PCNSL patients. Presented at the American Society of Radiation Oncology, October 2001, San Francisco, California.     

原发中枢神经系统淋巴瘤40例治疗与预后分析

目的 比较不同治疗方法对原发中枢神经系统淋巴瘤患者的有效性及安全性.方法 收集40例原发中枢神经系统淋巴瘤患者,分为3组,其中单纯手术组10例、手术联合化疗组15例、手术联合放化疗组15例,对3组进行生存分析比较.结果 随访7~53个月,中位生存时间手术联合放化疗组(45个月)和手术联合化疗组(30个月)高于单纯手术组(17个月),差异均有统计学意义(P均<0.05).3 a生存率手术联合放化疗组(72.2%)高于手术联合化疗组(40.8%)和单纯手术组(27.3%,P均<0.05).结论 手术联合放化疗可有效治疗原发中枢神经系统淋巴瘤,且患者耐受性好.     

Intravenous Methotrexate as Initial Treatment for Primary Central Nervous System Lymphoma: Response to Therapy and Quality of Life of Patients

In anticipation of a consortium study of methotrexate (MTX) therapy provided to patients with primary central nervous system lymphoma (PCNSL) we have provided intravenous MTX without irradiation therapy to 31 non-immunosuppressed individuals. Twenty (65%) achieved complete response and 11 (35%) partial response to therapy. For the 31 patients the median survival was 30.43 months with an actuarial median follow up time of 30.69 months. The 2+ year survival was 63% for all patients and 90% for complete responders. Of 375 drug cycles, grade 3 leukopenia was identified in 3 cycles, mucositis in 6 cycles and delayed drug clearance in 47 cycles. Recurrences included brain (9/20) and/or spinal fluid (2/20). The median Karnofsky scale improved from 40 (10–80) prior to therapy to 90 after treatment. Eleven patients, in complete response for a median of 22+ months after diagnosis were evaluated using 4 instruments that assess Quality of Life Functional Assessment of Cancer Therapy – Brain (FACT-BR) modified, Symptom Questionnaire, Social Adjustment Scale-Self-Report and Problem Solving Inventory. Their psychosocial adjustment, well-being and stress coping abilities were comparable to the normative groups. Further there was no evidence of any MTX-induced, Magnetic Resonance Imaging (MRI)-detected encephalopathy in these individuals and there was preservation of clinical cognition and memory. We conclude that therapy with MTX, without radiation can be used in PCNSL patients without limitations of age or pretreatment Karnofsky scores. Further rates of response and median survival approach those of therapies using multiple drugs and radiation, but with a less likely risk of dementia.