scholarly journals Immunogenicity of high-dose influenza vaccination in patients with primary central nervous system malignancy

2018 ◽  
Vol 5 (3) ◽  
pp. 176-183
Author(s):  
Roy E Strowd ◽  
Gregory Russell ◽  
Fang-Chi Hsu ◽  
Annette F Carter ◽  
Michael Chan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Influenza Vaccine ◽  
Elderly Patients ◽  
Influenza Vaccination ◽  
Standard Dose ◽  
High Grade Glioma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Central Nervous System Malignancy

Abstract Background For cancer patients, rates of influenza-associated hospitalization and death are 4 times greater than that of the general population. Previously, we reported reduced immunogenicity to the standard-dose influenza vaccine in patients with central nervous system malignancy. In other poorly responding populations (eg, elderly patients), high-dose vaccination has improved efficacy and immunogenicity. Methods A prospective cohort study was designed to evaluate the immunogenicity of the Fluzone® high-dose influenza vaccine in brain tumor patients. Data on diagnosis, active oncologic treatment, and immunologic status (eg, CD4 count, CD8 count, CD4:CD8 ratio) were collected. All patients received the high-dose vaccine (180 µg). Hemagglutination inhibition titers were measured at baseline, day 28, and 3 months following vaccination to determine seroconversion (≥4-fold rise) and seroprotection (titer ≥1:40), which were compared to our prior results. Results Twenty-seven patients enrolled. Diagnoses included high-grade glioma (85%), CNS lymphoma (11%), and meningioma (4%). Treatment at enrollment included glucocorticoids (n = 8, 30%), radiation (n = 2, 7%), and chemotherapy (n = 9, 33%). Posttreatment lymphopenia (PTL, CD4 ≤ 200) was observed in 4 patients (15%). High-dose vaccination was well tolerated with no grade III-IV toxicity. Overall, seroconversion rates for the A/H1N1, A/H3N2, and B vaccine strains were significantly higher than in our prior study: 65% vs 37%, 69% vs 23%, and 50% vs 23%, respectively (all P < .04). Seroconversion was universally poor in patients with PTL. While seroprotection at 3 months declined in our prior study, no drop was observed following high-dose vaccination in this cohort. Conclusions The immunologic response to HD influenza vaccination was higher in this cohort than standard-dose influenza vaccination in our prior report. These findings mirror those in elderly patients where high-dose vaccination is the standard of care and raise the possibility of an immunosenescence phenotype.

scholarly journals Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3479
Author(s):  
Andrea Morales-Martinez ◽  
Fernando Lozano-Sanchez ◽  
Alberto Duran-Peña ◽  
Khe Hoang-Xuan ◽  
Caroline Houillier
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Treatment Strategies ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
Current Treatment ◽  
Cns Lymphoma ◽  
High Dose ◽  
Consolidation Phase

The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.

Immunologic response to high-dose influenza vaccination in patients with primary central nervous system malignancy (PCNSM).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e20669-e20669
Author(s):  
Roy E. Strowd ◽  
Gregory Russell ◽  
Michele Harmon ◽  
Annette F Carter ◽  
Michael D Chan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Influenza Vaccination ◽  
High Dose ◽  
Immunologic Response ◽  
Central Nervous System Malignancy

Lymphomatous meningitis in primary central nervous system lymphoma

2006 ◽  
Vol 21 (5) ◽  
pp. 1-7 ◽  
Author(s):  
Marc C. Chamberlain
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Therapy ◽  
Mr Imaging ◽  
Primary Cns Lymphoma ◽  
Chemotherapeutic Agents ◽  
Cranial Computed Tomography ◽  
Cns Lymphoma ◽  
High Dose ◽  
Lymphomatous Meningitis

✓Lymphomatous meningitis (LM) due to primary central nervous system (CNS) lymphoma is an uncommon problem in neurooncology and can occur at time of diagnosis or recurrence. Notwithstanding frequent focal signs and symptoms, LM is a disease affecting the entire neuraxis, and therefore staging and treatment need to encompass all cere-brospinal fluid (CSF) compartments. Central nervous system staging of LM includes contrast agent–enhanced cranial computed tomography (CT) or Gd-enhanced magnetic resonance (MR) imaging, Gd-enhanced spinal MR imaging, CT myelography, and radionuclide CSF flow study. Treatment of LM includes involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy can benefit patients with LM and can obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (methotrexate, cytosine arabinoside, and thiotepa) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of LM is palliative and the expected median survival of patients is 4 to 6 months, it often provides stabilization and protection from further neurological deterioration. In patients with primary CNS lymphoma, CNS prophylaxis has been recommended (using a combination of high-dose systemic chemotherapy and intra-CSF chemotherapy), but the strategy remains controversial because high-dose systemic methotrexate is commonly used as an adjuvant therapy. Patients with primary CNS lymphoma at high risk as defined by positive CSF cytology or neuroradiography consistent with LM may benefit from the inclusion of intra-CSF chemotherapy.

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 &lt; 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.

Methotrexate and Temozolomide Plus Intrathecal Liposomal Cytarabine for Primary or Secondary Central Nervous System Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4899-4899
Author(s):  
Lorenzo Falchi ◽  
Marco Gunnellini ◽  
Ilaria Angeletti ◽  
Laura Franco ◽  
Anna Marina Liberati
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Contrast Enhancement ◽  
Cell Lymphoma ◽  
Cns Lymphoma ◽  
Liposomal Cytarabine ◽  
Delayed Neurotoxicity ◽  
Cns Prophylaxis

Abstract Abstract 4899 Treatment of central nervous system (CNS) lymphoma remains challenging, and balance between therapeutic effectiveness and toxicity is difficult to find. The addition of systemic chemotherapy to whole brain radiotherapy has significantly improved the outcome of these patients. However, this combined strategy is burdened with possible acute and/or delayed severe neurotoxicity, particularly in elderly patients. Chemotherapy-only approaches, with or without concomitant intrathecal (IT) therapy, for CNS lymphoma have been explored. Moreover, deferring radiotherapy to the time of first or subsequent relapse may reduce the risk of severe neurotoxicity, without altering outcome. Recently, high-dose methotrexate and temozolomide (HD-MTX-TMZ) without IT CNS prophylaxis have been studied in PCNSL elderly patients. This regimen appears effective, while substantially decreasing acute and/or delayed neurotoxicity. Conflicting data exist regarding the safety of combining IT liposomal cytarabine (LC) and systemic CNS-penetrating therapy. We report our preliminary experience with HD-MTX-TMZ plus IT LC used upfront or as salvage in 4 primary or secondary CNS lymphoma patients, only one of which under the age of 60 (56). Treatment consisted of induction: MTX 3g/ms d 1, 10, 20, TMZ 100 mg/ms d 1–5; and maintenance for ≥SD patients, and for up to 5 additional cycles: MTX 3g/ms d 1, TMZ 100 mg/ms d 1–5, every month. Fifty mg IT LC were given concomitantly for up to 6 doses planned. LC doses were separated by at least 14 days from one another and at least 7 days from HD-MTX. Pt n. 1 (56 year-old male) had a history of testicular diffuse large B cell lymphoma (DLBCL), stage IVA. He received chemo-radiotherapy with 4 concomitant IT LC injections as CNS prophylaxis. Complete response (CR) was achieved. Two months later, he presented with headache and dizziness. MRI and PET revealed metabolically active righ cerebellar lesion. Karnofsky performance status (KPS) was 50%. Rituximab plus TMZ and IT MTX were initiated but soon discontinued due to a G4 CMV-related pneumonia. After complete recovery, HD-MTX-TMZ was started with concomitant 4 IT LC injections, and precautionary stem cell harvest. No significant G3-4 toxicities were observed during treatment. At 9 months of follow-up post-treatment, the lesion is stable with no contrast enhancement at MRI and PET is negative, suggesting a CRu. Pt 2 (76 year-old male) was referred in May 2009 with a diagnosis of CNS peripheral T-cell lymphoma not otherwise specified with MRI- and PET-documented multiple brain localizations (i.e. hypophyseal infundibulum, cavernous sinus, cerebellum). KPS was 60%. He was treated with systemic steroids and TMZ 150 mg/ms d 1–5/28. In August 2009 disease progressed after two cycles, and HD-MTX-TMZ was started. IT LC was added as CNS prophylaxis with 4 drug injections. Toxicity consisted of G2 renal insufficiency and G3 steroid-induced diabetes mellitus, both resolved. Treatment resulted in marked shrinkage of all lesions, with no contrast enhancement and PET is negative, indicating CRu, which is stable at 5 months of follow-up. Pt 3 (68 year-old female) was diagnosed with PCNSL, DLBCL, with left cerebellar localization. KPS was 50%. HD-MTX-TMZ and concomitant IT LC injections were initiated as first-line therapy. Four maintenance cycles and 5 IT LC injections have been performed so far. Toxicities included G3 atrial fibrillation. Interim MRIs documented very good partial remission of the disease. Pt 4 (71 year-old female) was diagnosed with DLBCL stage IIIE (i.e. subcutaneous facial localization) in July 2009, and treated with R-COMP (liposomal doxorubicine in lieu of the free formulation) for 8 cycles. She obtained CR, but in July 2010 presented with aphasia and facial hemiparesis. Brain MRI showed multiple subcortical lesions in both hemispheres, biopsy-confirmed to be lymphoma. The first IT LC injection and HD-MTX dose were given without significant toxicity. All patients completed induction and 5 maintenance cycles. HD-MTX-TMZ and concomitant IT LC therapy appeared feasible and overall well tolerated. No acute neurologic complications were observed. Follow-up is too short to make comments on delayed neurotoxicity. Increasing the number of LC injections might be reasonable and at least 7 days should be interposed between systemic and IT therapy. HD-MTX-TMZ plus IT LC deserves further evaluation in a larger prospective setting. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Assessing Steroid Toxicity in the Elderly with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5557-5557
Author(s):  
Vidhya Nair ◽  
Hadi Mohammed ◽  
Sharmeen Mahmood ◽  
Pushpinderdeep Singh Kahlon ◽  
Philip Kuriakose
Keyword(s):  
Central Nervous System ◽  
Multiple Myeloma ◽  
Nervous System ◽  
Adverse Effects ◽  
Elderly Patients ◽  
Dose Reduction ◽  
The Elderly ◽  
High Dose ◽  
Full Dose ◽  
Starting Dose

Background The mainstay of treatment for Multiple Myeloma (MM) includes various combinations of chemotherapy, which generally includes high dose steroids. The median age at diagnosis for MM is above 60 years. Patients above the age of 70 may not be considered for an auto peripheral blood transplant, resulting in being treated with chemotherapy alone. This often leads to a relatively long period of steroid exposure. Increasing age is a risk factor for decreased tolerance to steroids, and increased drug toxicity. As such, the steroid dose (usually Dexamethasone) is often considered for reduction in patients above a certain age. However, there are no clear guidelines regarding a standard dose to use in the elderly, nor is there uniformity among clinicians in the way doses are chosen. Purpose To assess a) the starting dose of Dexamethasone (dex) in the elderly, b) frequency of dose reduction of dexamethasone, c) adverse effects of dex treatment in the elderly with MM, and d) average time after dose reduction. Methods We performed a 10 year retrospective chart review on patients, age 70 or greater treated at Henry Ford Health System with a diagnosis of MM from 2000-2015. Patients were grouped by age 70-75 years, 76-80 years, and greater than 80 years based on when treatment was initiated. We investigated the starting treatment dose of dex, ranging from 1-20 mg weekly and 21-40 mg weekly. Secondly, we assessed for the occurrence of dose reduction; and, if present, the length of time to reducing the dose. Lastly, the types of adverse effects to dex leading to dose reduction were grouped by system, such as, central nervous system, musculoskeletal, endocrine, gastrointestinal and psychiatric. Data collected was categorical, thus, no statistical tests were performed as this was a descriptive study. Results A total of 150 patients were reviewed and 91 patients met the inclusion criteria. Of these patients, 8 (8.8%) were started at doses between 1-20 mg and majority (62.5%) were ages 70-75, thus, there was no relation between lower starting dose and age. Of the 91 patients, 24 (26.4%) had a dose reduction and 11 (12.1%) had both chemotherapy and dex discontinued prior to therapy completion. Majority (87.5%) of patients that had a dose reduction were initially started at 40 mg. The reasons for dose reduction included adverse effects grouped by musculoskeletal (29.17%), psychiatric (16.67%), endocrine (12.3%), central nervous system (4.17%), and gastrointestinal (4.17%). Of note, 8 patients (33.3%) had dose reductions as result of their clinical trial requirement. The average length of dex therapy before dose reduction was 17.2 months. Conclusion The majority of elderly patients (age 70 or above) with MM tolerated full doses of dex without adverse effects. Secondly, there was no relation between lower starting dose for dex and advanced age. However, since there were limited patients (n=8) who started at a low dose, other than those on clinical trials, we were not able to do a comparison of starting doses. But we were able to show that the majority of patients tolerated full dose, despite their age. The most frequent cause of steroid toxicity was musculoskeletal, such as leg swelling. On average, elderly patients were able to tolerate full dose of dex for over 1 year prior to requiring a dose reduction. Summary Our data demonstrates no correlation between advanced age in MM and lack of tolerability of high dose steroids. In conclusion, current findings do not justify reduced doses solely based on age alone. Future studies could include investigating statistical analysis on steroid exposure and survivorship. Disclosures Kuriakose: Alexion: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy.

scholarly journals Single-Agent Ibrutinib in Recurrent/Refractory Central Nervous System Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 783-783 ◽  
Author(s):  
Christian Grommes ◽  
Alessandro Pastore ◽  
Igor Gavrilovic ◽  
Thomas Kaley ◽  
Craig Nolan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adverse Events ◽  
Clinical Response ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Methotrexate Chemotherapy

Abstract BACKGROUND: Primary Central Nervous System Lymphoma (PCNSL) is an aggressive primary brain tumor with median progression free survival (PFS) after upfront methotrexate-based chemotherapy of 2-3 years. Outcome and treatment options are poor for recurrent/refractory (r/r) disease. Response rates (ORR) range between 30-60% with a PFS of 2-5 months. Ibrutinib has shown promising clinical response in Mantel cell lymphoma, CLL, and Waldenström. This trial investigates Ibrutinib in patients with r/r PCNSL and SCNSL. METHODS: Eligible patients had r/r PCNSL or Secondary CNS Lymphoma (SCNSL), age≥18, ECOG≤2, normal end-organ function, and unrestricted number of CNS directed prior therapies. In patients with SCNSL disease, systemic disease needed to be absent. RESULTS: Twenty patients were enrolled (3 at 560 mg; 17 at 840 mg). Median age was 69 (range 21-85); 12 were women. Median ECOG was 1 (0: 2, 1: 12, 2: 6). 65% had PCNSL and 35% SCNSL; 70% had recurrent disease. Eleven had parenchymal disease, 3 isolated cerebrospinal fluid (CSF) involvement and 6 both. Five grade 4 adverse events were observed in 4 patients (lymphopenia (2), sepsis (1), neutropenia (2)). Ten patients developed grade 3 toxicities, including lymphopenia in 3 patients, thrombocytopenia in 2, hyperglycemia in 2, lung infection in 2, neutropenia in 1, urinary tract infection in 1, colitis in 1, and fungal encephalitis in 1. The most common toxicities were hyperglycemia, anemia, and thrombocytopenia. After a median follow-up of 193 days, 19/20 patients were evaluated for response: 8 CR, 7 PR, 1 SD and 3 PD; 75% (15/20) ORR. The median PFS is 7.29 months (95% CI: 3.80-15.43 months (longest: 15.3 months)). The mean Ibrutinib concentration in the CSF 2h post administration at day 1 and 29 is 1.75 ng/mL (3.97 nM) and 2.51 ng/mL (5.6 nM) which is above the IC50 (1nM) required in vitro to reduce growth of lymphoma cells.An additional treatment arm has been added to the trial which will evaluate adverse events of the combination of ibrutinib and high-dose methotrexate chemotherapy. Enrollment into the combination arm is ongoing and updates will be presented at the meeting. CONCLUSION: Patients with CNS lymphoma tolerate Ibrutinib with manageable adverse events. Drug concentrations in CSF are higher at steady state (day 29) and meaningful CSF concentrations are reached. Clinical response was seen in 75% of CNS lymphoma patients. A combination arm will assess the adverse events of ibrutinib in combination with high-dose methotrexate chemotherapy. Disclosures No relevant conflicts of interest to declare.

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