Primary Central Nervous System B-cell Research Articles

ABCL-038 HIV Status Affects Access to Autologous Stem Cell Transplant in Primary Central Nervous System B-Cell Lymphomas in a Minority Rich, Ethnically Diverse and Socioeconomically Disadvantaged Population at Montefiore Medical Center/Albert Einstein College of Medicine

Primary CNS lymphoma (PCNSL) is a rare, aggressive neoplasm showing frequent relapses. Though autologous stem cell transplant (ASCT) has shown survival benefits, data regarding access to and outcomes of ASCT in racial minorities and socioeconomically disadvantaged groups is limited. To identify variables, such as race/ethnicity, socioeconomic status (SES), and HIV status, associated with access to ASCT and outcomes in patients with PCNSL. Retrospective cohort including patients from 06/01/2000 to 04/05/2022. Tertiary oncologic center. Fifty-three PCNSL patients with a median age at diagnosis of 63 years were included. The cohort was 7% Asian, 29% Black, 27% Hispanic, 17% White, and 20% other. Eighteen percent of the patients were HIV positive, thrice the global prevalence of HIV in PCNSL patients. Electronic health records were reviewed. SES was measured using the area deprivation index (ADI), composed of 17 categories and validated for a range of health outcomes and disease domains (Kind et al. NEJM 2018). Correlation of different demographic variables with access to ASCT and overall survival (OS). The most common induction chemotherapy and conditioning regimens were remdesivir and TBC (thiotepa, busulfan, and cyclophosphamide), respectively. Our population had a higher poverty index than the national average (median NY state ADI: 5th percentile). Thirty-two percent of the patients in our cohort received ASCT (17/53), better than the national average of 12.9% in PCNSL patients in 2020. In a logistic regression model, HIV-positive status was significantly associated with decreased access to ASCT (P=0.01). ADI and race/ethnicity did not affect access to ASCT. One-year OS was 80%, and no significant difference was found between those treated with ASCT and those who were not. Median OS was not reached in ASCT recipients. When adjusted for the other variables, Karnofsky scores >90 at diagnosis were associated with increased access to ASCT (P=0.04). In our population, HIV positivity limited access to ASCT, but race/ethnicity did not. Neighborhood disadvantage (ADI) also did not affect access to ASCT as patients were within a narrow range of extremely low socioeconomic status. Analyzing larger datasets of HIV-positive individuals with PCNSL can provide further insights into factors affecting ASCT access and outcomes.

Alteration of BAFF and APRIL in the cerebrospinal fluid based on the therapeutic response in primary central nervous system B-cell lymphoma

We evaluated the cerebrospinal fluid (CSF) levels of the B-cell activating factor of the tumor necrosis factor family (BAFF) and A proliferation-inducing ligand (APRIL) in two cases of primary central nervous system B-cell lymphoma (PCNSBL) before and after treatment. One patient achieved clinical remission, and demonstrated decrease in the CSF levels of both BAFF and APRIL after treatment. Meanwhile, the other patient with insufficient therapeutic response showed increase in the BAFF levels despite decrease in APRIL levels. This report suggests that the combination of BAFF and APRIL levels could be useful in estimating the therapeutic efficacy in treating PCNSBL as reliable CSF markers.

Technical and anatomical aspects of endoscopically assisted septostomy in unilateral ventriculoperitoneal shunt placement for the management of isolated lateral ventricles

Abstract Background Isolated lateral ventricle is a specific form of non-communicating hydrocephalus that is caused by an obstruction of the foramen of Monro. The condition was previously treated with bilateral shunt placement. However, the emergence of endoscopic surgery has provided more options in the management of this condition. Case description 46-year-old female presented with obstructive hydrocephalus caused by a right thalamic primary central nervous system B-cell lymphoma. Endoscopic septostomy with unilateral shunt placement was performed because of bilateral foramen of Monro obstruction. Conclusion Endoscopic septostomy can be used as a tool to avoid bilateral shunt placement in certain cases of bilateral isolated lateral ventricles.

Isolated leptomeningeal infiltration of a primary CNS B-cell lymphoma diagnosed by flow cytometry and confirmed by necropsy

The diagnosis of the isolated leptomeningeal involvement of a primary central nervous system B-cell lymphoma without parenchyma lesions may be difficult. Patients with leptomeningeal meningeosis lymphomatosa can present with various neurologic deficits. To demonstrate the impact of cerebrospinal fluid (CSF) flow cytometry in the diagnosis of an isolated leptomeningeal manifestation of B-cell lymphoma by presenting an interesting case report. Flow cytometric analysis of B-cell monoclonality of the CSF was performed as complementary diagnostic procedure in addition to CSF cytology. Final diagnosis was confirmed by necropsy. We suspected isolated leptomeningeal manifestation of B-cell lymphoma with palsy of the VI and VII cranial nerves in a 79-year-old male, because of mononuclear pleocytosis in CSF. Interestingly, the decisive diagnostic hint was given by implementation of flow cytometry of the CSF. Diagnosis was confirmed by postmortem autopsy. Our case shows that flow cytometry of the CSF in addition to conventional CSF cytology has the potential to accelerate diagnosis of lymphomeningeal infiltration of B-cell lymphoma.

A Collision Tumor: Primary Central Nervous System B-Cell Lymphoma and Anaplastic Astrocytoma

A collision tumor in the central nervous system (CNS) is a rare entity. We report a case of a collision tumor with primary CNS lymphoma and astrocytoma in an otherwise healthy young male and the diagnostic challenge associated with it. The tumor showed 2 histologic patterns. The predominant component consisted of anaplastic astrocytoma with gemistocytic appearance, and the lymphoma cells were kappa restricted B cells with variable cell sizes and some plasmacytoid differentiation. In situ hybridization demonstrated that the lymphoma cells were Epstein-Barr virus (EBV) positive. The patient was neurologically asymptomatic for 2 and half years following surgery, chemotherapy, and radiation.

The Development of Primary Central Nervous System B-Cell Lymphoma in Multiple Sclerosis

When coupled with classical clinical signs and symptoms, magnetic resonance imaging can significantly aid in the diagnosis of multiple sclerosis (MS). However, the differential diagnosis of multiple sclerosis is large and, in the absence of pathognomonic clinical features, can be challenging to diagnose initially. Some conditions, such as primary central nervous system lymphoma (PCNSL) and progressive multifocal leukoencephalopathy (PML), can mimic clinically some of the symptoms prominent in multiple sclerosis. Early treatment with corticosteroids can dramatically improve patient symptoms in MS and PCNSL. We report a case of a man diagnosed with histologically confirmed relapsing remitting multiple sclerosis who subsequently developed histologically confirmed primary central nervous system lymphoma. Immunosuppressant therapy in the treatment of multiple sclerosis may be a potential catalyst in the development of central nervous system lymphoma. The course of his disease and treatment are presented and the current literature reviewed.

Meningioma interdigitated with primary central nervous system B-cell lymphoma: A case report and literature review

Background:Simultaneous presentation of multiple primary central nervous system (CNS) malignancies is extremely rare. There have been only eight cases of meningiomas co-existing with primary cerebral lymphoma, reported in the literature.Case Description:We present a case of a patient who underwent surgical resection of an olfactory grove meningioma that was interdigitated with a primary CNS B-cell lymphoma. Following surgery, the patient was treated with high-dose methotrexate, and has no evidence of recurrence after 18 months.Conclusion:Because of the early recognition of these two distinct pathologies, the patient received directed adjuvant therapies, and has exceeded the survival of all other cases reported in the literature.

Intrathecal Administration of Rituximab for the Treatment of Primary Central Nervous System B-Cell Lymphoma.

Background: Patients with a primary central nervous system (CNS) lymphoma are very difficult to be treated. Regarding elderly patients, the side effects of the established strategies are considerable, particularly those caused by radiotherapy. Although with poor long term results, surgery, high dose chemotherapy and focal radiotherapy have been advised for these patients. Thus, new therapeutics strategies are needed. We report two cases of primary CNS B-cell lymphomas treated with rituximab intrathecally (ith). Case 1: In September 2003, a 59-year-old female with headache, paresthesia and weakness of the right limbs presented at our clinic. In August 2003 a brain biopsy of a parenchymal lesion was performed, vasculitis and cerebritis were found. The patient's condition progressively worsened during the next 3 months and she developed a right-side hemiparesis. A PCR test to ascertain the presence of Mycobacterim tuberculosis in brain tissue was positive and rifampicin was prescribed. The patient presented at our clinic in September 2003, and in December 2003 she underwent another brain biopsy and CD20+ diffuse large B-cell lymphoma was diagnosed. Chemotherapy with high-dose methotrexate (MTX) 3.5 g/m2 iv, MTX 12 mg ith and vincristine 1.4 mg/m2 was scheduled every 15 days for a total of 5 cycles. The patient experienced a partial remission. In February 2004, rituximab 25 mg ith was administered on days 1–2 and days 8–9. There was no toxicity during, or after the rituximab infusions. In March, after a total dose of 200 mg, there was a complete radiological remission of the lymphoma and a consistent clinical improvement. In June 2004, the lymphoma relapsed, affecting the same area of the brain and in July 2004 a re-treatment protocol consisting of MTX 8g/m2 and high dose cytarabine was started, without response. The patient died of sepsis, secondary to mucositis and pancytopenia in August 2004. Case 2: a 67-year-old male with a primary malignant B lymphoma CD20+ of the posterior fossa which relapsed after two surgeries, high dose chemotherapy and focal radiotherapy with lymphomatous meningitis. Complete remission was obtained after one course of high dose MTX (4g/m2) and intrathecal MTX, intercalated with three courses of systemic (350 mg/m2) and intrathecal rituximab (25mg/d - 8 days). The patient presented hepatotoxicity after the first dose of MTX iv. The relapse free survival is seven months until now and the patient is physically and intellectually fully recovered. No major side effects were observed with the administration of rituximab intrathecally.Conclusion: Intrathecal administration of rituximab had no toxicity and was well-tolerated. Further studies are necessary to establish the best dose and schedule to achieve an improvement in the therapeutic response.

Routine use of real-time quantitative PCR for laboratory diagnosis of Epstein-Barr virus infections.

Real-time quantitative polymerase chain reaction (PCR) on the LightCycler instrument (LC-PCR) was developed to measure the Epstein-Barr virus (EBV) load in clinical samples. LC-PCR detected two copies of the EBV genome per 500 ng of DNA. Its specificity was confirmed by assays in EBV-negative cell lines, other human herpesviruses and EBV-seronegative individuals. Excellent inter-assay reproducibility of LC-PCR was obtained in 43 samples (r = 0.983). LC-PCR results were compared with a routinely used ELISA-PCR of 150 samples and a good correlation was found (r = 0.956). A total of 88 individuals were studied, including healthy EBV-seropositive adults (n = 32), patients with EBV-associated disease (n = 34), and HIV-infected patients (n = 22); 37.5% of PBMC samples from healthy individuals contained EBV DNA, while no serum sample was positive. The viral load was significantly higher in PBMCS and saliva specimens in patients recently infected with HIV (19 and 39,400 copies/microg DNA, respectively), as well as in AIDS patients (122 and 331,130 copies/microg DNA) than in the control population (0 and 35 copies/microg DNA). This study confirmed that EBV load measurement with LC-PCR is helpful in the management of EBV-related post-transplantation lymphoproliferative disorders and probably of EBV-associated primary central nervous system B-cell lymphoma.