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

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.

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Complete Response After High-Dose Methotrexate-Based Chemotherapy as a Major Prognostic Factor for Primary CNS Lymphoma: An Exploratory Analysis of the LNHCP93 Trial of the Groupe d'Etude Des Lymphomes De l'Adulte.

Blood ◽

10.1182/blood.v114.22.101.101 ◽

2009 ◽

Vol 114 (22) ◽

pp. 101-101

Author(s):

Hervé Ghesquières ◽

Celine Ferlay ◽

Agathe Bajard ◽

Catherine Sebban ◽

David Perol ◽

...

Keyword(s):

Multivariate Analysis ◽

Prognostic Factor ◽

Performance Status ◽

Primary Cns Lymphoma ◽

Complete Response ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Methotrexate ◽

Dose Methotrexate ◽

Status Number

Abstract Abstract 101 Background: Treatment of primary CNS lymphoma (PCNSL) is based on high-dose methotrexate (HD-MTX) containing chemotherapy (CT) followed by brain radiotherapy (RT). Initial CT allowed 30% to 63% of complete response (CR) in recent large series. After CT, consolidation RT can increase the CR rate up to 80%. Despite this high rate of response after initial treatment, the outcome of patients remained poor. The impact of the quality of response on outcome is not well known as well as the outcome of PR patients who converted to CR after RT. We assessed these questions in patients with newly diagnosed PCNSL treated with HD-MTX-containing CT followed by RT in the prospective LNHCP93 GELA study. Methods: 99 patients were treated in this prospective phase II study between 1995 and 2002. Patients younger than 61 years received C5R protocol (Blay et al. Blood 1995), Patients aged 61-70 years received reduced doses of C5R protocol and patients older than 70 years received a specific schedule with MTX, vepeside and cyclophosphamide. After CT, brain RT was planned: 20 Gy whole brain and a 36 Gy boost to the tumor bed. Responses after CT and after RT were evaluated by MacDonald criteria. Evaluation of response was made at time of the beginning of RT, 21-35 days after the last course of CT, and one month after the end of RT. Results: Median age of the 99 PCNSL patients was 63 years (range, 20-82), 51% were male, 51% had performance status >1, and 58% had involvement of deep structures of brain. Forty-five patients were younger than 61 years, 36 were aged 61-70 years and 18 older than 70 years. After a median follow-up 83 months, median overall survival (OS) and progression-free survival (PFS) were 33 and 20 months, respectively. Seventeen patients (17%) died of acute toxicity during CT; 3 patients (3%) did not receive RT; 8 patients (8%) progressed or had stable disease after CT and 3 patients (3%) had no available data. Thus, 68 patients were assessable for this exploratory study with thirty-six patients (36%) in PR and 32 patients (32%) in CR after CT. Sixteen of PR patients converted to CR after RT (44% of PR patients after CT). Median OS of patients in CR and PR after CT was 80 and 34 months with a 5-year OS probability of 65% and 29%, respectively (p=0.02). Median PFS of patients in CR and PR after CT was 60 and 21 months with a 5-year PFS probability of 56% and 17%, respectively (p=0.03). In univariate and multivariate analysis, age and response were the two prognostic factors for OS but not performance status, number of tumors at diagnosis, site of tumor (involvement of deep structures). Only response to CT was predictive of PFS in multivariate analysis but not age, performance status, number of tumors, site of tumor at diagnosis. 5-year OS was 65% for CR patients before RT compared to 31% and 28% for PR patients who converted to CR after RT and for patients not in CR after RT, respectively (p=0.06). The 5-year PFS probability was 56% for CR patients before RT compared to 13% and 20% for patients who converted to CR after RT and those not in CR after RT, respectively (p=0.09). Conclusion: Despite the inherent bias of response analysis as a prognostic factor, this analysis of a prospective study of PCNSL patients showed that only patients achieving CR after CT may experience long term survival. This study also showed that PR patients who converted to CR after RT had a poor outcome, similar to patients that did not reach a CR after chemoradiotherapy. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v112.11.3591.3591 ◽

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.1534 ◽

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.

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

Blood ◽

10.1182/blood.v110.11.1364.1364 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1364-1364 ◽

Cited By ~ 1

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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Prognostic model for primary CNS lymphoma (PCNSL): Recursive partitioning analysis (RPA) of the MSKCC PCNSL population

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.1531 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 1531-1531 ◽

Cited By ~ 1

Author(s):

L. E. Abrey ◽

L. Benporat ◽

K. S. Panageas ◽

J. Yahalom ◽

L. M. Deangelis

Keyword(s):

Overall Survival ◽

Prognostic Model ◽

Proportional Hazards ◽

Prognostic Score ◽

Performance Status ◽

Univariate Analysis ◽

Primary Cns Lymphoma ◽

Cox Proportional Hazards ◽

Cns Lymphoma ◽

Analysis And Design

1531 Background: Increasingly there is a need to develop a simple prognostic score that can be used in the analysis and design of PCNSL studies as well as for clinical management. Recently the IELSG published a 3 group prognostic model incorporating patient age, performance status, serum LDH, location of brain lesions and CSF total protein; however, only 105 of their 378 patients had all of the variables available to develop this score. Methods: We analyzed 338 patients (median age 60; median KPS 70) seen and treated for PCNSL at MSKCC between 1983 and 2003. The median survival was 37 months and median follow up of surviving patients is 35 months. Univariate analysis of potential prognostic factors was performed using the Kaplan Meier product limit method. Significant univariate variables were included in a multivariate analysis using the Cox proportional hazards regression model. Patients were separately analyzed using the IELSG prognostic score. Finally, RPA was employed as an independent method of developing specific prognostic categories. Results: In the univariate analysis, age, hemiparesis, mental status changes, creatinine clearance and KPS were significant predictors of overall survival; in the multivariate model only age and KPS remained as significant predictors. 113 patients had adequate information (all 5 variables) to be analyzed using the IELSG prognostic score; while this correlated significantly with overall survival, the comparison between groups 2 and 3 was not statistically significant (p = 0.10). RPA of all 338 patients identified 3 subgroups: age ≤ 50 (median OS 9.2 y), age > 50 and KPS ≥ 70 (median OS 3.2 y) and age > 50 and KPS < 70 (median OS 1 y) that significantly separated our entire PCNSL population (p < 0.001). Conclusions: The use of RPA allows for easy discrimination of 3 prognostic groups of patients with PCNSL. In contrast to the IELSG score the MSK RPA classification includes information that is readily available on all patients and can be easily incorporated into the analysis or design of clinical research. No significant financial relationships to disclose.

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c-Kit (CD117) Expression Is a Poor Prognostic Factor for Relapse and Overall Survival in Patients with Newly Diagnosed AML.

Blood ◽

10.1182/blood.v108.11.4510.4510 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4510-4510

Author(s):

Cristina Rodriguez ◽

Tao Jin ◽

Rony Abou Jawde ◽

Wael Saber ◽

Rachid Baz ◽

...

Keyword(s):

Flow Cytometry ◽

Overall Survival ◽

Multivariate Analysis ◽

Induction Chemotherapy ◽

De Novo ◽

Newly Diagnosed ◽

Increased Risk ◽

The Mean ◽

Wbc Count ◽

Risk Of Relapse

Abstract Background: C-kit (CD117), a tyrosine kinase receptor, is expressed on most myeloid blasts and is thought to be important in the pathogenesis of AML. Activation of the c-kit receptor leads to phosphorylation and activation of downstream signaling proteins which are important for cell survival and proliferation. Previous studies have demonstrated conflicting results regarding the prognostic impact of c-kit expression. This discordance is likely secondary to limitations in the current method used to measure c-kit. The aim of this study was to evaluate c-kit quantitatively using the mean fluorescent index (MFI), and determine whether this index predicted outcome in patients with newly diagnosed AML. Methods: We conducted a retrospective review of 183 patients with newly diagnosed AML treated with induction chemotherapy at the Cleveland Clinic between January 1998 and December 2005. Flow cytometry was performed on bone marrow or peripheral blood. Blasts were stained with antibodies against CD45 and c-kit (BD Biosciences San Jose, CA). CD45-stained cells without c-kit antibody were used as a negative control. Flow cytometry was performed on FACS Caliber instruments, and data were acquired using Cell Quest software. Using a CD45/orthogonal gate to isolate blasts, the MFI was calculated as the mean channel number (MCN) of the blasts/MCN autofluorescence. Known prognostic factors including: age, WBC count at diagnosis, AML etiology (de novo vs. secondary AML) and cytogenetics (as defined by CALGB criteria) were obtained. Cox proportional hazards analysis was used to identify univariate and multivariate correlates of complete remission (CR), overall survival (OS), relapse after remission, and progression-free survival (PFS). Only variables significant in the univariate setting were included in multivariate analysis. Results were summarized as the hazard ratio (HR) with 95% confidence intervals (CI). Results: All patients underwent anthracycline-based induction chemotherapy. 96 (52.5%) patients were male with a median age of 57 years (17–79). Cytogenetics were favorable in 24 patients (13.1%), intermediate in 98 (53.6%), poor in 47 (25.7%) and unknown in 14 (7.6%). AML was secondary in 52 patients (28.4%) and de novo in 131 patients (71.6%). Median WBC count at diagnosis was 10.3 k/uL [4–259 k/uL]. 139 patients (76%) achieved a CR following induction chemotherapy, and 66 patients (36.1%) relapsed after achieving CR. Median c-kit MFI was 13.1 [0–251.1]. On univariate analysis, c-kit MFI(per 50 unit increase) was associated with an increased risk of AML relapse (HR=1.33 [CI=1.01–1.74 p=.041] ), and a trend towards inferior PFS and OS, HR=1.24 (CI=.97–1.57 p=.08) and HR=1.29 (CI=.99–1.67 p=.06), respectively. On multivariate analysis, c-kit MFI correlated with worse OS (HR=1.37 [CI=1.04–1.82 p=.026]) and an increased risk of relapse (HR=1.32 [CI=1.01–1.73 p=.043]). A trend towards decreased PFS was also seen, but did not reach statistical significance (HR=1.21 [CI=.96–1.53 p=.11]). Conclusion: C-kit MFI, independently of known prognostic factors, predicts OS and risk of relapse in patients with newly diagnosed AML. Whether inhibiting c-kit in patients with AML will alter prognosis is the basis of ongoing clinical trials.

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Rituximab-Lenalidomide-Ibrutinib Combination for Relapsed/Refractory Primary CNS Lymphoma

Neurology ◽

10.1212/wnl.0000000000012515 ◽

2021 ◽

Vol 97 (13) ◽

pp. 628-631

Author(s):

Caroline Houillier ◽

Cecile Moluçon Chabrot ◽

Marie-Pierre Moles-Moreau ◽

Lise Willems ◽

Guido Ahle ◽

...

Keyword(s):

Karnofsky Performance Status ◽

Performance Status ◽

Primary Cns Lymphoma ◽

Complete Response ◽

Rapid Onset ◽

High Rate ◽

Cns Lymphoma ◽

T Cell Therapy ◽

Heavily Pretreated ◽

Rate Of Response

Background and ObjectivesTo evaluate the efficacy and tolerance of the association rituximab-lenalidomide-ibrutinib (R2I) in relapsed/refractory (R/R) primary CNS lymphoma (PCNSL).MethodsR/R PCNSL patients treated with R2I were retrospectively selected and analyzed from the French LOC database.ResultsFourteen patients (median age: 63 years, median Karnofsky Performance Status: 75%) received R2I, administered after a median of 2 previous lines of chemotherapy, including autologous stem cell transplantation (ASCT) in 5 cases. The best response was complete response in 4/14 patients and partial response in 4/14 patients, achieved in a median of 2.5 months. Three responder patients received consolidation treatment (WBRT: N = 2, ASCT: N = 1) after R2I, and R2I served as a bridge before CAR-T cell therapy for one patient. R2I was discontinued due to toxicity in 3/14 patients. There were no toxicity-related deaths.DiscussionThe R2I combination resulted in a high rate of response of rapid-onset in heavily pretreated patients with poor prognosis, with manageable toxicity, and allowed 3 patients to proceed to consolidation. Although preliminary, these results support the use of R2I for R/R PCNSL failing conventional chemotherapies.Classification of EvidenceThis study provides Class IV evidence that combination of rituximab-lenalidomide-ibrutinib induces a high rate of response in heavily pretreated R/R PCNSL.

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

Scientific Reports ◽

10.1038/s41598-020-80724-0 ◽

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.

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How I treat primary CNS lymphoma

Blood ◽

10.1182/blood-2011-03-321349 ◽

2011 ◽

Vol 118 (3) ◽

pp. 510-522 ◽

Cited By ~ 100

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.

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