Significance of MYC rearrangement and chemotherapy type on survival outcomes of patients with central nervous system lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7548-7548
Author(s):  
Natalie Sophia Grover ◽  
Allison Mary Deal ◽  
Stephanie Mathews ◽  
Ashley Freeman ◽  
Christopher Dittus ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Statistical Significance ◽  
Performance Status ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Performance Status ◽  
High Dose ◽  
Single Institution ◽  
Significant Difference

7548 Background: Central nervous system lymphoma (CNSL) has a poor prognosis and an optimal treatment regimen has not been established. Due to the rarity of this disease and frequently poor performance status at diagnosis, there have been few prospective therapeutic clinical trials in this patient population. We therefore performed a retrospective analysis of prognostic factors and treatment outcomes of patients with CNSL treated at a single institution. Methods: Pathology records were used to identify patients diagnosed with CNSL from 1/1/2005 to 9/1/2016 at the University of North Carolina Cancer Hospital. Information about demographics, disease characteristics, treatment, and outcomes was gathered from the electronic medical record. Overall (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. Results: We identified 100 patients with CNSL. 49% had primary CNSL (PCNSL). 78% of cases were diffuse large B cell lymphoma. Out of 51 patients evaluated for MYC translocation by FISH, 13 were positive (3 PCNSL and 10 secondary CNSL). Out of 74 patients treated with chemotherapy, 51% received methotrexate (MTX), procarbazine, and vincristine (MPV), with or without rituximab, 28% were treated with other high dose MTX based regimens, with or without rituximab, and 20% received a non-MTX based regimen. There was no significant difference in OS between PCNSL and secondary CNSL (13.7 vs 7.9 months, p = 0.97). Patients with MYC translocation had a worse OS compared to those without MYC translocation (5.1 vs 29.5 months, p = 0.004). Patients treated with MPV had a longer PFS compared to those treated with other high dose MTX based regimens or those who were treated with a non-MTX based regimen (19.1 vs 10.9 vs 3.9 months, p = 0.05), but difference in OS did not reach statistical significance (29.5 vs 22.4 vs 10.6 months, p = 0.12). Conclusions: In this single institution analysis of CNSL, MYC translocation was associated with worse survival. MPV was associated with improved PFS compared to other chemotherapy regimens. Further prospective studies are needed comparing MPV to other MTX-based regimens in CNSL.

scholarly journals Treatment of secondary central nervous system involvement in systemic aggressive B cell lymphoma using R-MIADD chemotherapy: a single-center study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuchen Wu ◽  
Xuefei Sun ◽  
Xueyan Bai ◽  
Jun Qian ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cns Involvement ◽  
The Central Nervous System ◽  
Secondary Central Nervous System

Abstract Background Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined. Methods We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients. Results Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0–44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%). Conclusions These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.

scholarly journals Evaluation of The Effectiveness and Side Effects of Radiotherapy in Patients With Primary Nervous System Lymphoma. A Single Center Experience

2020 ◽  
Vol 7 ◽  
Author(s):  
Timur Koca ◽  
Aylin Fidan Korcum ◽  
Yasemin Şengün ◽  
Melek Gamze Aksu ◽  
Mine Genç
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Side Effects ◽  
Disease Free Survival ◽  
Central Nervous System Lymphoma ◽  
Field Size ◽  
High Dose ◽  
Free Survival ◽  
Significant Difference

Aim: In this study, we aimed to evaluate the overall and progression-free survival, the radiotherapy process and the early and late adverse effects in patients who underwent radiotherapy (RT) for primary nervous system lymphoma in our clinic.Method: Between January 2010 and September 2019, 16 patients who received radiotherapy due to primary central nervous system lymphoma in our clinic were examined according to their statistically significant differences in terms of survival and side effects.Results: The median disease-free survival of the patients was 6 months, and the median overall survival was 12.5 months. 18.75% of the patients could not receive chemotherapy but only radiotherapy. Radiotherapy doses were range from 2600 to 5000 cGy. When patients were evaluated in terms of radiotherapy dose, field size and chemotherapy, no statistically significant difference in overall survival was detected. Cognitive disorders were observed as the most common late side effects while the most common acute side effects in patients were headaches.Conclusion: In the treatment of primary central nervous system lymphoma, changes in radiotherapy portals and radiotherapy doses can be predicted in patients who received high-dose methotrexate chemotherapy or not. Furthermore, it has been considered that more comprehensive studies are needed to increase the success of treatment and provide standardization in treatment, especially in patients with elderly and comorbid diseases.

Primary and Secondary Central Nervous System Lymphoma: Outcomes from Houston Methodist Cancer Center

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Cesar Gentille Sanchez ◽  
Ethan Burns ◽  
Ibrahim Muhsen ◽  
Humaira Sarfraz ◽  
Carlo Guerrero ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cancer Center ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Female Ratio ◽  
Multiagent Chemotherapy

Introduction Primary Central Nervous System Lymphoma (PCNSL) is a rare form of extra-nodal non-Hodgkin Lymphoma (NHL), with diffuse large B-cell Lymphoma (DLBCL) reported in 90% of cases. Secondary CNS lymphoma (SCNSL) may occur as an isolated recurrence of previously diagnosed NHL or occur simultaneously as a manifestation of systemic disease. Comparative data on survival in treated PCNSL and SCNSL in the real-world setting is lacking. We present a retrospective analysis of outcomes in PCNSL and SCNSL patients treated at the Houston Methodist Cancer Center. Methods We retrospectively identified patients with a diagnosis of PCNSL or SCNSL from 2015 to 2020. Data collected included age, race, sex, diagnosis (PCNSL, SCNSL), histology and immunohistochemistry, treatment type (chemotherapy, radiation), transplant rates as well as outcomes (alive/dead). Responses were classified as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Survival was analyzed using Kaplan-Meier methodology, and log-rank tests were used to compare survival distributions. P < 0.05 was considered statistically significant. Results There were 50 patients with CNS lymphoma identified between 2015 and 2020; 68% were PCNSL. Out of 43 with available pathology, 2 patients were T-cell lymphomas and 41 DLBCL. Out of the DLBCL cases, 95% of cases expressed CD20 while close to 60% were positive for MUM1, bcl-2 and bcl-6. Less than 15% of cases were positive for CD10. CD30 was positive in 17% of cases. Cerebral hemispheres (76%) was the most common organ involved, followed by ocular (8%), intraventricular space (6%) and cerebellum (6%). Median age at diagnosis was 67 years; male to female ratio was 1.27. Caucasian (62%) and Hispanic (24%) were most common ethnicities. Epstein-Barr Virus was positive in 14% of patients (5 in PCNSL and 2 in SCNSL). One patient with SCNSL had human immunodeficiency virus. The median follow-up time was 9.1 months. Multiagent chemotherapy including high dose methotrexate (MTX), cytarabine and rituximab was given to 48% of the patients while 32% received high dose MTX alone plus rituximab. From the latter group, five out of sixteen patients received temozolomide. Other regimens were used in 6% of the cases. Median dose of MTX in a multiagent chemotherapy regimen was 2.5gr/m2 and 2.25gr/m2 when used alone or with temozolomide. Median number of cycles given was 3. Radiation therapy alone was given to 8% of cases. Three patients did not receive treatment. For patients with PCNSL, overall response rate (ORR) was 82.8% (CR 65.5%, PR 13.8%, SD 3.4%). ORRs were similar between multiagent chemotherapy and methotrexate alone (+/- temozolomide) with 86.7% and 83.3% respectively. ORR for SCNSL was 57.1% (CR 35.7%, PR 21.4%); only 1 patient was treated with MTX alone. Further lines of therapy were required in 9.3% of patients. Consolidation with whole brain radiation was given in 22% of the cases (29.4% for PCNSL and 6.3% for SCNSL). Autologous stem cell transplant was performed in 10% of the patients (2 PCNSL, 3 SCNSL). Overall survival for patients with PCNSL was 74.8 months and 10.1 months for SCNSL (p=0.0444) (Figure 1). Survival was not significant between patients receiving multiagent chemotherapy and MTX alone or in combination with temozolomide (3-year OS 57.3% vs 73.4%, p= 0.5652) (Figure 2). Conclusion Most patients diagnosed with PCNSL are non-germinal center DLBCL. Median MTX dose was lower than 3gr/m2 with excellent ORR of over 80% in PCNSL. Response rates were lower in SCNSL and in general, patients with PCNSL had better outcomes. Survival did not differ significantly between regimens, suggesting that a lower intensity therapy may perform similarly to multiagent chemotherapy. These results need to be confirmed by prospective studies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Primary Central Nervous System Lymphoma in an Immunocompetent Patient Presenting as Multiple Cerebellar Lesions: A Case Report and Review of Literature

2019 ◽  
Vol 7 ◽  
pp. 232470961989354
Author(s):  
Gliceida M. Galarza Fortuna ◽  
Kathrin Dvir ◽  
Christopher Febres-Aldana ◽  
Michael Schwartz ◽  
Ana Maria Medina
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Lesion ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Immunocompetent Patient ◽  
Cns Lymphoma ◽  
High Dose ◽  
Older Woman ◽  
Non Hodgkin Lymphoma

Primary central nervous system (CNS) lymphoma (PCNSL) is an uncommon extranodal non-Hodgkin lymphoma often presenting as a single brain lesion within the CNS. On histopathological evaluation of PCNSL a positive CD10, which is frequently observed in systemic diffuse large B-cell lymphoma, is present in approximately 10% of PCNSL. We describe a case of CD10-positive PCNSL presenting with multiple posterior fossa enhancing lesions in an immunocompetent older woman with a history of breast cancer successfully treated by the RTOG 0227 protocol consisting of pre-irradiation chemotherapy with high-dose methotrexate, rituximab, and temozolomide for 6 cycles, followed by low-dose whole-brain radiation and post-irradiation temozolomide.

What Is The Optimal Dose Of Methotrexate In Primary Central Nervous System Lymphoma Treatment Regimens?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3040-3040
Author(s):  
Samir Dalia ◽  
Samantha L Price ◽  
Peter Forsyth ◽  
Celeste M. Bello ◽  
Bijal D. Shah ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Total Dose ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Significant Difference ◽  
Treatment Data ◽  
Dose Reductions

Abstract Introduction Primary central nervous system lymphoma (PCNSL) is a rare disorder with a poor prognosis. The mainstay of treatment is single agent or combination high dose (≥3.5g/m2) methotrexate (HDMTX) based regimens. There is no consensus as to which dose of HDMTX improves outcomes in patients with PCNSL but doses of MTX greater than 3 g/m2 intravenously achieve therapeutic cerebrospinal fluid (CSF) concentrations. Purpose To determine if there is an optimal or total dose of HDMTX in PCNSL therapies that results in improved progression free (PFS) or overall survival (OS). Methods Patients at Moffitt Cancer Center with PCNSL were identified using our institutional database between January 1, 2000 and September 30, 2011. Patients with complete treatment data who were treated with HDMTX were included in this study. HDMTX was defined as MTX at a dose ≥ 3.5g/m2. Patient demographics, clinical, and treatment data were collected and analyzed. Treatment information collected included the starting dose of HDMTX, IV rituximab use, MTX toxicity and clearance, cycles of MTX, and total amount of MTX administered (g/m2). Data were analyzed using descriptive statistics and the Kaplan-Meier (KM) method was used to estimate median PFS and OS using the log rank test. P value of <0.05 was considered significant. All data was analyzed using SPSS statistical software version 21.0. Results A total of 51 patients were identified (Table 1). Median PFS was 13months (0-33) and median OS 43months (29-57). The addition of IV rituximab or other chemotherapy failed to improve PFS or OS. HDMTX dose reductions or the total dose of HDMTX administered did not significantly impact PFS or OS. Similarly, when comparing dosing of HDMTX there was no significant difference in 8g/m2 versus 3.5g/m2 (PFS p=0.56, OS p=0.68), or between patients receiving 8g/m2 versus <8g/m2 (PFS p=0.77, OS p=0.6) (Figure 1). Patients receiving 8g/m2 versus those receiving <8g/m2 of HDMTX had similar baseline characteristics except for more liver function abnormalities in the 8g/m2 group. Conclusions Differences in initial dosing of HDMTX or total dose of HDMTX therapy did not influence outcomes in our patients with PCNSL. Dose reductions in HDMTX, addition of other chemotherapeutic agents, or rituximab were not associated with improved PFS or OS. An intriguing plateau was observed in OS in the 8gm/m2 arm despite similar PFS, suggesting that the receipt of novel therapies in the relapsed setting may contribute to OS. Multicenter collaborative clinical trials are needed to further assess the optimal initial dose of HDMTX to administer in PCNSL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals ML-02 MULTIAGENT IMMUNOCHEMOTHERAPY, R-MPV-A, FOR PATIENTS WITH SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii32-ii32
Author(s):  
Motoo Nagane ◽  
Keiichi Kobayashi ◽  
Kuniaki Saito ◽  
Daisuke Shimada ◽  
Yoshie Matsumoto ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Response Rate ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
University Hospital ◽  
High Dose ◽  
Serious Adverse Events

Abstract BACKGROUNDS Standard of care (SOC) for primary central nervous system lymphoma (PCNSL) has been induction therapy with high-dose methotrexate (MTX)-based multiagent immunochemotherapies followed by consolidation, and we have shown that one such regimen, R-MPV-A have superior efficacy over HD-MTX alone with whole brain radiotherapy (WBRT). While SOC for secondary CNS involvement of systemic diffuse large B-cell lymphoma (DLBCL)(SCNSL) has not been established. Here we report the outcome of R-MPV-A for patients with SCNSL. PATIENTS AND METHODS Fifteen patients with SCNSL treated with R-MPV-A from January 2014 to January 2019 in Kyorin University Hospital were eligible. Prior treatment for systemic DLBCL was mostly R-CHOP. Response and survival outcomes were evaluated. RESULTS Median age was 68.0 y (55–84), male/female 6/9, median KPS 70 (40–90), histopathological confirmation was achieved in 12 patients (80%; biopsy 11). RMPV (rituximab+MTX+procarbazine+vincristine) 3 cycles in 3, 4–7 cycles in 6, 8 cycles in 5. WBRT and cytarabine were delivered in 6 and 9 patients, respectively. R-MPV resulted in 6 CRs/CRus, 5 PRs, 1 SD, and 2 PDs (Response rate 73%). R-MPV-A including consolidation led to 9 CRs/CRus, 2 PRs, 1 SD, and 2 PDs (complete response rate 60%). With median F/U period of 11.2 m (0.1–51.5), 1y-PFS and 2y-PFS of R-MPV-A were 66.0% and 56.6%, 1y-OS and 2y-OS were 72.2% and 72.2%, respectively. Median PFS/OS were not reached. Consolidation cytarabine was associated with better outcome. Three deaths occurred during the treatment (20%; two during R-MPV with aged 70s, KPS 40 and 50; one presented MTX clearance delay). No other serious adverse events were observed. CONCLUSIONS These results suggest the certain efficacy of R-MPV-A for SCNSL. Being heavily pretreated frequently, precautions should be taken to identify high risk cases.

scholarly journals NQPC-06 FUNCTIONAL OUTCOMES OF INITIAL TREATMENTS FOR PATIENTS WITH PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA ASSESSED BY ADL AND NEUROCOGNITIVE FUNCTION

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii30-ii30
Author(s):  
Mikiko Taku ◽  
Keiichi Kobayashi ◽  
Yuki Yamagishi ◽  
Kuniaki Saito ◽  
Daisuke Shimada ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Induction Therapy ◽  
Social Adjustment ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Central Nervous System Lymphoma ◽  
Neurocognitive Function ◽  
Remission Induction ◽  
High Dose

Abstract BACKGROUNDS Primary central nervous system lymphoma (PCNSL) frequently causes severe damage of activities of daily living (ADL) and neurocognitive function (NCF) due to extensive brain infiltration, necessitating their appropriate assessment and measures even in clinical practice. Since few studies have focused on the changes in the level of ADL and NCF in the course of PCNSL treatment, we retrospectively analyzed the effect of initial treatment of PCNSL in view of ADL and NCF. METHODS Among 55 patients (13 male/9 female) with newly-diagnosed PCNSL treated in our institution from January 2014 to June 2019, 22 were evaluated with both ADL and NCF. Remission induction therapies consisted of high-dose methotrexate alone (two patients), R-MPV (rituximab, methotrexate, procarbazine, and vincristine)(17 patients), and R-MPV+radiaotherapy (three patients), according to the patients’ conditions. Rehabilitation staffs intervened from the beginning, providing specific exercises and periodically evaluating scores of Karnofsky Performance Status (KPS) and Mini Mental State Examination (MMSE). RESULTS Mean age was 68.4 yo (range 34 to 85). After induction therapies, there were 11 complete responses (CRs), eight partial responses (PRs), and three progressive diseases (PDs). Both KPS and MMSE scores improved after induction therapy, from median 70 (40–90) to 80 (50–90), and from 24 (0–30) to 27(0–30), respectively. Among three patients who underwent RT, MMSE declined in two (one CR/one PR). CONCLUSIONS Case-adjusted induction therapies resulted in significant radiographical responses, and the longitudinal evaluation of ADL and NCF by rehabilitation staffs could validate their maintenance or improvement over time through effective treatments and early rehabilitation intervention. However, three was difficulty in assessing patients with higher brain dysfunction such as aphasia and social adjustment disorder. Further study is needed to include more patients and to explore more appropriate evaluation batteries and timings during and after completion of induction therapy for PCNSL.

A rare type primary central nervous system lymphoma with primarily psychiatric diagnosis- a case report

2017 ◽  
Vol 41 (S1) ◽  
pp. S489-S490
Author(s):  
U. Cikrikcili ◽  
B. Saydam ◽  
M. Aktan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Neuropsychiatric Symptoms ◽  
Clinical Manifestations ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Histopathological Diagnosis ◽  
High Grade

Primary central nervous system lymphoma (PCNSL) is a high-grade malignant B-cell non-Hodgkin neoplasm that is an infrequent variant of all intracranial neoplasms (1%) and all lymphomas (< 1%)PCNSL is documented mainly in immunocompromised patient groups, although it may also be diagnosed in immunocompetent patients. It affects mainly the eyes, supratentorial areas, or the spinal cord. The lesions are typically localized in frontal lobes, corpus callosum and basal ganglia. Additionally, lesions might rarely be detected at infratentorial areas and in medulla spinalis. Even though a wide spectrum of treatment options are available, such as chemotherapy, radiotherapy, or surgery; response rates are low and prognosis is poor in spite of appropriate treatment.The case we reported here is 57-year-old male presented with symptoms of aggresivity, impulsivity, depressive mood and personality changes. Histopathological diagnosis was CD5 positive diffuse large B cell lymphoma, which is very rare in high-grade lymphomas. There were no neurological signs related to CNS tumor and the clinical manifestations responded very well to chemotherapy consisting of high dose methotrexate, vincristine and procarbazine. The significance of such neuropsychiatric symptoms in the course of treatment for PCNSL has been previously documented as well. These behavioral and emotional symptoms might manifest themselves based on where the neoplasm is localized. Therefore, psychiatrists should be more aware of the uncommon manifestation of the disorder as reported in this case. Consultation for differential diagnosis might also be necessary in such cases.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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