Characteristics and outcomes of elderly patients with primary CNS lymphoma (PCNSL)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2070-2070
Author(s):  
D. E. Ney ◽  
A. S. Reiner ◽  
H. D. Skinner ◽  
K. S. Panageas ◽  
L. M. DeAngelis ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Salvage Therapy ◽  
Primary Cns Lymphoma ◽  
Initial Therapy ◽  
Cns Lymphoma ◽  
Small Subset ◽  
High Dose ◽  
Chemotherapeutic Regimen ◽  
Systemic Involvement ◽  
Entire Cohort

2070 Background: The incidence of PCNSL is increasing and is highest in those ≥ 65 years of age. Systemic chemotherapy (CT) ± radiotherapy (RT) improves survival, but treatment related toxicity is greatest in this population. The optimal treatment has yet to be determined. The aim of this study was to characterize older patients with PCNSL at our institution and identify outcomes related to treatment. Methods: We identified patients ≥ 65 years of age treated for PCNSL from 1986 to 2008. Charts were reviewed for demographics, treatment details, tumor progression, and survival. Approval for this study was obtained from the IRB at MSKCC. Results: 174 patients were identified with a median age of 72 years (range: 65–89). 60% of patients had a stereotactic biopsy for diagnosis; 93% had a histologic or cytologic diagnosis. 14 patients had evidence of systemic involvement with detailed staging evaluation. 82% of patients received a high-dose methotrexate (3.5g/m2) regimen, only 13% did not receive CT. Among the patients who received CT, 76% had a radiographic response (CR+PR), 3% had stable disease while 12% progressed. Only 26% had RT as part of initial therapy. CR rate to initial therapy was 67%, 52% of these patients eventually relapsed. Median time to progression was 24 months (range: 1–91). Among the patients who relapsed, 85% received salvage therapy consisting of CT (n = 42), RT (n = 14), or both (n = 7) while 15% received no further treatment. 48% of patients had a CR or PR to salvage therapy while 26% had PD; the remainder were not evaluated. Median overall survival for the entire cohort was 25 months (range: 0.5 to 177+) with a 3-year survival of 36%. 17% developed late treatment-related neurologic toxicity. Administration of RT was associated with the development of neurotoxicity (p < 0.0001). 39 patients remain alive with a median follow-up of 34 months (range: 0.5–177). Conclusions: Elderly patients can receive an aggressive chemotherapeutic regimen with good outcomes. Systemic staging is also valuable as a small subset of patients will have systemic involvement at diagnosis. Clinical trials to optimize treatments for this population are critical. No significant financial relationships to disclose.

Elderly patients with primary CNS lymphoma: Results from the G-PCNSL-SG-1 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2007-2007
Author(s):  
Patrick Roth ◽  
Peter Martus ◽  
Philipp M. Kiewe ◽  
Robert Moehle ◽  
Hermann A. Klasen ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Salvage Therapy ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
The Elderly ◽  
Response To Therapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Younger Patients ◽  
The Impact

2007 Background: Age is the most important therapy-independent prognostic factor in patients with primary central nervous system lymphoma (PCNSL). Here we aimed at providing an analysis of the impact of higher age on response to therapy, toxicity, and survival in the largest PCNSL trial ever performed to date. Methods: Response to therapy, toxicity and survival of PCNSL patients enrolled in the G-PCNSL-SG-1 trial evaluating the role of radiotherapy after high-dose methotrexate (HD-MTX)-based chemotherapy were monitored. Subjects aged 70 or more were compared to younger patients. Results: Of all eligible patients (n=526), 126 (24%) were aged 70 or more. In the per protocol population, 66 of 318 patients (21%) were at least 70 years old. Among the eligible patients, the rate of complete and partial responses (CR+PR) to HD-MTX-based chemotherapy was 44% in the elderly compared to 57% in the younger patients (p=0.016). A higher rate of grade III/IV leukopenia was observed in the elderly (34% versus 21%, p=0.007). Also, death on therapy was more frequent (18% versus 11%; p=0.027) in these patients. In contrast, there was no other major age-dependent toxicity. Survival analyses revealed shorter progression-free survival (PFS) (4.0 versus 7.7 months, p=0.014) and overall survival (OS) (12.5 versus 26.2 months, p<0.001) in the elderly population. The PFS of CR patients was 35.0 months in younger patients compared to 16.1 in the elderly (p=0.024). Salvage therapy was used less commonly in elderly patients. When salvage WBRT was applied in patients who had failed on HD-MTX-based chemotherapy, there was no association between age and survival (p=0.633). Conclusions: Elderly PCNSL patients have a lower response rate and higher mortality on HD-MTX-based chemotherapy. Their PFS is shorter and they receive less salvage therapy which may contribute to the poor prognosis.

scholarly journals ACTR-25. RETHINKING THE DOGMA: HOW IMPORTANT IS TREATMENT OF THE CSF IN PATIENTS WITH PRIMARY CNS LYMPHOMA (PCNSL)?

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi18-vi18
Author(s):  
Dawit Aregawi ◽  
Agnieszka Korfel ◽  
Uwe Schlegel ◽  
Michael Glantz
Keyword(s):  
Initial Treatment ◽  
Primary Cns Lymphoma ◽  
Initial Therapy ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Csf Cytology ◽  
Group Iii ◽  
Group Ii

Abstract INTRODUCTION PCNSL constitutes a small but important fraction of adult malignant primary brain tumors. These tumors frequently and often dramatically respond to high-dose methotrexate-containing regimens, but almost inevitably recur. Following initial treatment and at the time of recurrence, no widely accepted treatment paradigm exists. In particular, no consensus exists regarding the need to treat the CSF at the time of PCNSL diagnosis. METHODS We identified three independent cohorts of adults with PCNSL in which some patients received intra-CSF chemotherapy as part of their initial therapy, and others did not. All patients were comparable with respect to demographic and disease characteristics (study-level data). Data on CSF involvement, response, relapse, and survival were extracted and summary statistics were calculated from these three studies using the inverse variance method and random effects model. RESULTS The three cohorts were treated with: HD MTX/rituximab/ifosfamide followed by either HD MTX/cytarabine/ifosfamide (group Ia), or cytarabine/thiotepa and autologous stem cell transplant (group Ib) (n=80); HDMTX/rituximab/vinca alkaloids/ifosfamide/cytarabine (group II) (n=48); or HD MTX/rituximab (group III). Intra-CSF chemotherapy consisted of MTX/cytarabine/prednisolone (group Ia only, n=43); MTX/cytarabine/prednisolone (group II, n=30); or liposomal cytarabine (group III, n=21). One- and two-year survivals were greater in the IT chemotherapy compared to the no-IT chemotherapy groups (RR 1.25 [1.16–1.34] and 1.20 [1.14–1.26] respectively, p&lt; 0.001 for both). Relapse involving the CSF was greater in the non-IT chemotherapy group (RR 2.31 [2.03–2.62], p&lt; 0.001). In one cohort, comparison of pre-treatment CSF cytology from ventricular vs lumbar sites was possible. CSF cytology was positive in 81% of ventricular specimens vs 14.3% of lumbar specimens (p&lt; 0.0001). CONCLUSIONS CSF involvement by tumor occurs in most patients with PCNSL. Including intra-CSF chemotherapy in the initial treatment regimen of these patients may improve overall survival and reduce the frequency of relapses involving the CSF. Well-designed prospective trials are warranted.

scholarly journals High-dose methotrexate for elderly patients with primary CNS lymphoma

2009 ◽  
Vol 11 (2) ◽  
pp. 211-215 ◽  
Author(s):  
Jay-Jiguang Zhu ◽  
Elizabeth R. Gerstner ◽  
David A. Engler ◽  
Maciej M. Mrugala ◽  
Whitney Nugent ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Immuno-Chemotherapy with Rituximab, Methotrexate, Lomustine, and Procarbazine for the Treatment of Primary CNS Lymphoma in Patients >65 Years.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3712-3712
Author(s):  
Kristina Fritsch ◽  
Benjamin Kasenda ◽  
Anna Markert ◽  
Jürgen Finke ◽  
Gerald Illerhaus
Keyword(s):  
Elderly Patients ◽  
Conflicts Of Interest ◽  
Alkylating Agents ◽  
Objective Response ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Karnofsky Performance Score

Abstract Abstract 3712 Poster Board III-648 Introduction Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma (NHL) confined to the CNS and/or eyes at presentation. PCNSL have a poor prognosis dispite good initial response to steroids and whole brain irradiation (WBRT). Addition of high-dose methotrexate (MTX) to therapy has improved the prognosis of patients with PCNSL, resulting in median survival rates of up to 60 months (mo). However, most patients eventually relapse. Surviving patients, particularly elderly treated with combined radio-chemotherapy are at substantial risk of developing leukoencephalopathy. We developed a protocol with high-dose MTX combined with the lipophilic alkylating agents procarbacine and lomustine and the anti-CD20 monoclonal antibody rituximab (R-MPL protocol), especially adapted for elderly patients with PCNSL. Here we report the results of 28 patients treated with combined immuno-chemotherapy with R-MPL protocol within a monocentric study. Methods Patients ≥65 yrs with PCNSL were treated with up to 3 cycles of R-MPL protocol: rituximab (375mg/m2 d-6, 1, 15, 29), MTX (3g/m2 d2, 16, 30), procarbazine (60 mg/m2 p.o., d1-10) and lomustine (110 mg/m2 p.o., d1). Cycles were repeated d42. Inclusion criterias were age ≥65 yrs and biopsy proven PCNSL. There was no lower limit of Karnofsky Performance Score. Results 28 patients (median age 75 yrs., range 65-83 yrs.) received R-MPL protocol. 2 patients died, one due to pulmonary embolism 2 weeks after initiation of treatment, the other had a perforation of the sigmoid and both were not evaluable for response. Objective response was seen in 25 of 26 patients (96,2%) with 19 CR and 6 PR. In 5 patients, MTX was not tolerated after 1 (n=4) and 2 (n=1) applications due to cholestatic hepatitis (n=1) and renal impairment (n=4). 2 patients with refractory disease could successfully be salvaged with AraC/thiotepa (n=1) and HDT and ASCT (n=1), respectively. 5 patients experienced relapse and could not be salvaged. After a median follow-up of 26 mo (range 2-35) 10 patients (35,7 %) are alive and disease-free. By intend-to-treat-analysis the 12-mo and 24-mo is 69% and 52% respectively. Severe leukoencephalopathy has not been observed. Most recent follow-up data will be presented in detail. Conclusion The immuno-chemotherapy protocol presented here is safe and shows high efficacy in treating elderly patients with PCNSL. A prospective phase-II trial will be initiated. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High-dose chemotherapy and autologous stem cell transplant in elderly patients with primary CNS lymphoma: a pilot study

2020 ◽  
Vol 4 (14) ◽  
pp. 3378-3381
Author(s):  
Elisabeth Schorb ◽  
Benjamin Kasenda ◽  
Gabriele Ihorst ◽  
Florian Scherer ◽  
Julia Wendler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Elderly Patients ◽  
Stem Cell Transplant ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Key Points

Key Points Age-adapted high-dose chemotherapy and autologous stem cell transplantation is safe and highly effective in elderly patients with PCNSL.

scholarly journals HDMTX-based polychemotherapy including intraventricular therapy in elderly patients with primary CNS lymphoma: a single center series

2020 ◽  
Vol 13 ◽  
pp. 175628642095108
Author(s):  
Sabine Seidel ◽  
Thomas Kowalski ◽  
Michelle Margold ◽  
Alexander Baraniskin ◽  
Roland Schroers ◽  
...  
Keyword(s):  
Complete Remission ◽  
Elderly Patients ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Cerebrospinal Fluid Leak ◽  
Ommaya Reservoir ◽  
Cns Lymphoma ◽  
High Dose ◽  
Karnofsky Performance Score

Background: To investigate outcome and toxicity of high-dose systemic methotrexate (HDMTX)-based polychemotherapy and intracerebroventricular (ICV) chemotherapy via an Ommaya reservoir in elderly patients with primary central nervous system lymphoma (PCNSL). Methods: We performed a retrospective analysis on patients ⩾65 years with first diagnosis of PCNSL admitted to our center between January 2015 and December 2019. These patients were treated with a standardized chemotherapy protocol in case of absent contraindications for HDMTX-based chemotherapy. The protocol contained induction therapy with systemic rituximab, methotrexate and ifosfamide and consolidation treatment with systemic cytarabine (AraC) and ICV methotrexate, prednisolone and AraC. Results: Of a total of 46 patients seen in this period, 3 did not qualify for HDMTX. Thus, 43 patients were included in this analysis. Median age was 74 years (range 65–86), median Karnofsky performance score was 50 (range 20–90). Of the 43 patients, 32 (74.4%) completed treatment including ICV therapy. Complete remission/complete remission unconfirmed was achieved in 26 of 43 patients (60.5%), partial response (PR) in 3 (7%); 5 (11.6%) had progressive disease, and 3 (7.0%) died due to treatment-related complications; in the remaining 6 (14.0%) therapy could not be completed. Median progression free survival was 16 months (95% confidence interval 8–24 months) and median overall survival had not been reached after a median follow up of 23 months (range 1–52 months); the 75th percentile survival time was 12 months. No Ommaya reservoir infection was observed. Complications of ICV treatment were pericatheter leucencephalopathy in two patients and surgical scar dehiscence with cerebrospinal fluid leak in one patient. Conclusion: Toxicity of HDMTX plus ICV chemotherapy for elderly patients with PCNSL was manageable and outcome was excellent for patients treated with this protocol.

First-line temozolomide therapy and MGMT status in elderly patients with primary CNS lymphoma

2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
M Glas ◽  
D Kurzwelly ◽  
P Roth ◽  
K Rasch ◽  
E Weimann ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
First Line

scholarly journals SS-4 High dose chemotherapy with autologous hematopoietic stem cell transplantation for CNS lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii2-ii2
Author(s):  
Eisei Kondo
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Hematopoietic Stem

Abstract High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDT-ASCT) is listed as a consolidation therapy option for primary central nervous system (CNS) lymphoma in the guidelines of western countries. The advantages of HDT-ASCT for primary CNS lymphoma as consolidation are believed to be high rates of long-term remission and lower neurotoxicity, even though its eligibility is limited to younger fit patients. In the Japanese guideline, HDT-ASCT for primary CNS lymphoma is however not recommended in daily practice, mainly because thiotepa was unavailable since 2011. The Japanese registry data for hematopoietic transplantation have shown that primary CNS lymphoma patients were treated with various HDT regimens and thiotepa-containing HDT was associated with better progression free survival (P=.019), lower relapse (P=.042) and a trend toward a survival benefit (Kondo E et al, Biol Blood Marrow Transplant 2019). A pharmacokinetic study of thiotepa(DSP-1958) in HDT-ASCT for lymphoma was conducted in 2017, and thiotepa was approved for HDT-ASCT in lymphoma this March, meaning that optimal HDT regimen for CNS lymphoma is now available in Japan. The treatment strategy of CNS lymphoma needs further development to improve survival and reduce toxicity.

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