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British Journal of Haematology Jan 2021A few prospective trials in HIV-positive patients with Burkitt lymphoma (BL) or high-grade B-cell lymphoma (HGBL) have been reported. Investigated therapies have shown...
A dose-dense short-term therapy for human immunodeficiency virus/acquired immunodeficiency syndrome patients with high-risk Burkitt lymphoma or high-grade B-cell lymphoma: safety and efficacy results of the "CARMEN" phase II trial.
A few prospective trials in HIV-positive patients with Burkitt lymphoma (BL) or high-grade B-cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose-dense, short-term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36-day polychemotherapy induction followed by high-dose cytarabine-based consolidation and response-tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)- conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV-positive adults (median age 42, range 26-58; 16 males) with untreated BL (n = 16), HGBL (n = 3) or double-hit lymphoma (n = 1) were enrolled. All patients had high-risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non-haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47 days; interquartile range 41-54), was complete in 13 patients and partial in five [overall response rate = 90%; 95% confidence interval (CI) = 77-100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow-up of 55 (41-89) months, 14 patients are relapse-free and 15 are alive, with a five-year progression-free survival and an overall survival of 70% (95% CI = 60-80%) and 75% (95% CI = 66-84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability.
Topics: Acquired Immunodeficiency Syndrome; Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Burkitt Lymphoma; Carmustine; Cytarabine; Etoposide; Female; HIV Infections; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, B-Cell; Male; Melphalan; Middle Aged; Transplantation, Autologous
PubMed: 33085777
DOI: 10.1111/bjh.17188 -
Journal of Virus Eradication Feb 2020Adults living with HIV have an increased risk of malignancy yet there is a paucity of data for adolescents and young adults (AYA) with perinatally acquired HIV (PaHIV).
BACKGROUND
Adults living with HIV have an increased risk of malignancy yet there is a paucity of data for adolescents and young adults (AYA) with perinatally acquired HIV (PaHIV).
METHODS
Retrospective cohort analysis of all-cause mortality and malignancies in AYA with PaHIV aged 10-24 years attending a tertiary unit from 01 January 2004 to 31 December 2017, assessing cancer presentation, immunology and comparing mortality and malignancy incidence to age-matched UK general population rates.
RESULTS
A total of 290 AYA with PaHIV contributed 2644 person-years of follow up. Six (2.0%) died within the study period at a median age of 17 years (interquartile range [IQR]15-19), 3 of malignancy, 2 with end-stage HIV and 1 with cryptococcal meningitis. Overall mortality rate was 2.3/1000 person-years, with an age-matched general population rate of 0.2/1000 person-years. Eight (2.8%) were diagnosed with a malignancy; 6 with lymphoma (=3 Hodgkin's, =1 Burkitt's, =2 B-cell) and one each with hepatocellular carcinoma and gastrointestinal adenocarcinoma. At cancer diagnosis the median age was 19 years (IQR 14-23), median CD4 T cell count was 453 cells/mm (IQR 231-645) and median length of HIV viremia was 15 years (IQR 12-17). The incidence rate of a malignancy was 3.0/1000 person-years in AYA with PaHIV, whilst that in the age-matched general population is 0.2/1000 person-years.
CONCLUSION
AYA living with PaHIV had an increased risk of all-cause mortality and of malignancy compared to their uninfected peers, with the excess in malignancy driven by lymphomas. It is hoped that earlier access to antiretroviral therapy will mitigate some of the AIDS-defining and non-AIDS defining risks for future generations.
PubMed: 32175089
DOI: No ID Found -
BMJ Case Reports Oct 2021Cerebral phaeohyphomycosis refers to central nervous system infection by dematiaceous mould or by dark walled fungi which contain the dark pigment melanin in their cell...
Cerebral phaeohyphomycosis refers to central nervous system infection by dematiaceous mould or by dark walled fungi which contain the dark pigment melanin in their cell wall which adds to the virulence of fungus. These dematiaceous fungi can cause a variety of central nervous infections including invasive sinusitis, brain abscess, meningitis, myelitis and arachnoiditis. among these dematiaceous fungi is the most common cause of brain abscess in immunocompetent and immunocompromised individuals and is known to occur worldwide though is predominantly reported from subtropical regions especially the Asian subcontinent. It is difficult to differentiate these abscesses radiologically from high-grade gliomas, primary central nervous system lymphoma or other infections including toxoplasmosis, nocardiosis, tuberculosis and listeriosis. We describe a 19-year-old male patient with a cerebral abscess caused by where the diagnosis could be suspected by typical MR spectroscopic findings and by identifying the fungus from a lymph node biopsy.
Topics: Adult; Antifungal Agents; Ascomycota; Brain Abscess; Humans; Immunocompromised Host; Lymphadenitis; Male; Young Adult
PubMed: 34706919
DOI: 10.1136/bcr-2021-246108 -
BioRxiv : the Preprint Server For... Dec 2023Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor...
Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor survival outcomes. We utilized comprehensive multi-omics analyses of CSF from patients with lymphoma LMD to demonstrate an immunosuppressive cellular microenvironment and identified dysregulations in proteins and lipids indicating neurodegenerative processes. Strikingly, we found a significant accumulation of toxic branched-chain keto acids (BCKA) in the CSF of patients with LMD. The BCKA accumulation was found to be a pan-cancer occurrence, evident in lymphoma, breast cancer, and melanoma LMD patients. Functionally, BCKA disrupted the viability and function of endogenous T lymphocytes, chimeric antigen receptor (CAR) T cells, neurons, and meningeal cells. Treatment of LMD mice with BCKA-reducing sodium phenylbutyrate significantly improved neurological function, survival outcomes, and efficacy of anti-CD19 CAR T cell therapy. This is the first report of BCKA accumulation in LMD and provides preclinical evidence that targeting these toxic metabolites improves outcomes.
PubMed: 38187773
DOI: 10.1101/2023.12.18.572239 -
British Journal of Haematology Nov 2019
Topics: Humans; Lymphoma, B-Cell; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Middle Aged
PubMed: 31423572
DOI: 10.1111/bjh.16163 -
Brain Tumor Research and Treatment Oct 2019Only sporadic reports of fluorescence-guided surgery (FGS) have been published for non-glioma conditions. In this study, we focus on epidemiological data of fluorescence...
BACKGROUND
Only sporadic reports of fluorescence-guided surgery (FGS) have been published for non-glioma conditions. In this study, we focus on epidemiological data of fluorescence patterns and report the diverse experiences of FGS in non-gliomas.
METHODS
During 8.5 years between July 2010 and January 2019, 900 FGS for brain tumor performed in Seoul National University Hospital. Among them, a total of 73 histologically proven non-glioma patients were analyzed. Indications for FGS have been the possibility of anaplastic tumor in intra-axial tumors in preoperative MRI and an attempt to reproduce known anecdotal experiences of 5-Aminolevulinic Acid (5-ALA) fluorescence.
RESULTS
In cases of brain tumors except for gliomas, the most frequent cases were brain metastasis (23 cases) followed by lymphomas (9 cases) and meningeal tumors (8 cases). And there were embryonal tumors (6 cases), hemangioblastomas (4 cases), and solitary fibrous tumor/hemangiopericytomas (3 cases). Most brain metastases, meningiomas, primary central nervous system lymphomas, and treatment effect cases showed positive fluorescence. Moreover, some non-tumorous conditions also showed positive fluorescence. However, hemangioblastoma and germ cell tumor did not observe any fluorescence at all.
CONCLUSION
5-ALA induced fluorescence is not limited to glioma but is also evident in non-glioma and non-neoplastic conditions. This 5-ALA-induced fluorescence may be used as an intraoperative tool for various brain conditions.
PubMed: 31686441
DOI: 10.14791/btrt.2019.7.e39 -
Biomedicine & Pharmacotherapy =... Jan 2022Polymerase chain reaction (PCR) analysis of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid (CSF) remains vital for evaluating active EBV infection involving the... (Review)
Review
Polymerase chain reaction (PCR) analysis of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid (CSF) remains vital for evaluating active EBV infection involving the central nervous system (CNS). CSF EBV DNA was often found in conjunction with other microbial infection affecting the CNS among patients infected with human immunodeficiency virus (HIV). Sometimes CSF EBV DNA is detectable in patients without neurological symptoms. This review focused on the clinical and laboratory features of CNS EBV infection among patients with HIV, and discussed various types of EBV-associated CNS infections, and predominant neoplasms involving CNS such as primary central nervous system lymphoma (PCNSL), CNS-non-Hodgkin's lymphoma, smooth muscle tumors and leiomyosarcomas, EBV encephalitis or myelitis, EBV meningitis and EBV coinfection with other causative agents were also included. Furthermore, the metagenomic next-generation sequencing technique with high sensitivity for the detection of pathogenic coinfection in the CSF were also reviewed. We concluded that CSF EBV-DNA detection with high sensitivity and specificity could be a useful diagnostic tool for CNS lymphoma among HIV patients; however, it is still unknown for other CNS diseases. We further summarized and conclude that positive CSF EBV-DNA detection combined with specific brain focal lesions could be a minimally invasive method to diagnose PCNSL. The occurrence of positive CSF EBV-DNA was influenced by PCR detection limit, PCR methods, immunocompromised status, the possible influence of anti-herpetic therapy and anti-HIV therapy, and the size and location of a tumor mass. Uniform PCR methods as vital diagnostic tools and optimal EBV-DNA load threshold need to be established.
Topics: Central Nervous System Diseases; Central Nervous System Neoplasms; DNA, Viral; Epstein-Barr Virus Infections; HIV Infections; High-Throughput Nucleotide Sequencing; Humans; Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 34781140
DOI: 10.1016/j.biopha.2021.112392 -
Indian Journal of Hematology & Blood... Apr 2020We report a case of a 26-year-old man diagnosed with nasal-type extranodal natural killer/T cell lymphoma (ENKTL) extending beyond the nasal cavity. Complete response...
OBJECTIVES
We report a case of a 26-year-old man diagnosed with nasal-type extranodal natural killer/T cell lymphoma (ENKTL) extending beyond the nasal cavity. Complete response was achieved after therapy, followed by rapid metastasis to the meningeal nerve fibres. The overall survival (OS) of the patient was 15 months. To better understand ENKTL with meningeal involvement, we summarized the clinical features of the 10 cases involving meningeal metastasis in ENKTL reported in the English literature.
METHODS
The patient was admitted for the ENKTL diagnosis, and positron emission tomography-computed tomography showed the disease stage and response. When central nervous system (CNS) infiltration was suspected, magnetic resonance imaging (MRI) of the brain and spinal cord was performed, as well as cerebrospinal fluid (CSF) analysis with flow cytometric immunophenotyping.
RESULTS
MRI of the brain and spinal cord revealed normal results. CSF analysis with flow cytometric immunophenotyping showed NK/T lymphoma cell infiltration.
CONCLUSION
Meningeal metastasis of ENKTL is rare; when patients present with nervous system symptoms, CNS metastasis should be considered as a possibility, even in the early stage. The OS of our patient was 15 months, which is the longest survival time reported in the literature, probably due to early diagnosis and comprehensive management, including intrathecal therapy, chemotherapy and radiotherapy of the whole brain and spinal cord.
PubMed: 32425394
DOI: 10.1007/s12288-019-01234-2 -
Cancer Medicine Jan 2020Marginal zone lymphoma of the central nervous system (CNS MZL) is rare. The clinical features, treatment, and prognosis are not well characterized. We performed a...
An international multicenter retrospective analysis of patients with extranodal marginal zone lymphoma and histologically confirmed central nervous system and dural involvement.
Marginal zone lymphoma of the central nervous system (CNS MZL) is rare. The clinical features, treatment, and prognosis are not well characterized. We performed a multicenter retrospective study of CNS MZL. Twenty-six patients were identified: half with primary and half with secondary CNS involvement. The median age was 59 years (range 26-78), 62% female and 79% with ECOG performance status ≤ 1. The most common disease site was the dura (50%). Treatment was determined by the treating physician and varied substantially. After a median follow up of 1.9 years, the estimated 2-year progression-free (PFS) and overall survival (OS) rates were 59% and 80%, respectively. Secondary CNS MZL was associated with 2-year OS of 58%. CNS MZL is rare, but relative to other forms of CNS lymphoma, outcomes appear favorable, particularly among the subset of patients with dural presentation and primary CNS presentation.
Topics: Adult; Aged; Central Nervous System Neoplasms; Combined Modality Therapy; Dura Mater; Female; Follow-Up Studies; Humans; Lymphoma, B-Cell, Marginal Zone; Male; Middle Aged; Prognosis; Retrospective Studies; Survival Rate
PubMed: 31808316
DOI: 10.1002/cam4.2732 -
Thoracic Cancer Sep 2022The prognosis of non-small-cell lung cancer (NSCLC) with leptomeningeal metastasis (LM) is poor. Detection of cell-free DNA (cfDNA) by next generation sequencing (NGS)...
BACKGROUND
The prognosis of non-small-cell lung cancer (NSCLC) with leptomeningeal metastasis (LM) is poor. Detection of cell-free DNA (cfDNA) by next generation sequencing (NGS) in cerebrospinal fluid (CSF) may facilitate diagnosis of LM and identification of drug resistance mechanisms, yet its clinical use needs to be further verified.
METHODS
We performed a retrospective cohort study to assess the genetic profiles of paired CSF and plasma samples in lung cancer patients with LM. Of 17 patients screened, a total of 14 patients with LM and paired NGS tests were enrolled.
RESULTS
All patients harbor driver gene mutations, including 12 epidermal growth factor receptor (EGFR) activating mutations, 1 anaplastic lymphoma kinase (ALK) rearrangement, and 1 ROS-1 fusion. Genetic mutations were detected in CSF cfDNA from 92.9% patients (13/14), which was significantly higher than that from the plasma (9/14, 64.2%). The mutations were highly divergent between CSF and plasma cfDNA, with a concordance rate of 24.38% and 10 mutations shared by the two media. CSF cfDNA could also benefit the analysis of resistance mechanisms to targeted therapies. In five patients who experienced progression on 1st or 2nd generation EGFR-tyrosine kinase inhibitors (TKIs), RB1 mutation, and amplification of MET and EGFR were detected in CSF cfDNA only. In eight patients with LM progression on osimertinib resistance, EGFR amplification was detected in CSF cfDNA from four patients, whereas no CNVs were detected in the matched plasma samples.
CONCLUSIONS
In conclusion, CSF could be superior to plasma in providing a more comprehensive genetic landscape of LM to find out drug resistance mechanisms and guide subsequent treatments.
Topics: Carcinoma, Non-Small-Cell Lung; Cell-Free Nucleic Acids; ErbB Receptors; Genotype; Humans; Lung Neoplasms; Meningeal Carcinomatosis; Mutation; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 35896160
DOI: 10.1111/1759-7714.14592