NCMP-15. IMMUNE CHECKPOINT INHIBITOR ENCEPHALITIS: A RETROSPECTIVE COHORT STUDY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi150-vi150
Author(s):  
Nathan Clarke ◽  
Merry Chen
Keyword(s):  
Rare Complication ◽  
Single Agent ◽  
Specific Treatment ◽  
Retrospective Chart Review ◽  
High Dose ◽  
Specific Class ◽  
Permanent Disability ◽  
Check Point Inhibitors ◽  
Post Infusion ◽  
Cancer Types

Abstract OBJECTIVE To review our institution’s experience with immune check point inhibitors (ICI) in patients with all cancer types and describe the incidence and outcomes of encephalitis associated with its use. METHODS We performed a single-center retrospective chart-review identifying patients who developed encephalitis within 12 weeks of treatment with an ICI. RESULTS Between 2011 to 2020 we identified 842 unique patients treated with an ICI with 32 patients (3.8%) developing encephalitis associated with treatment. The median time to diagnosis was 20 days post infusion (13-24 days IQR) and 3 infusions (2-4 IQR). No specific treatment was more significantly associated with encephalitis than the rest with the combination of ipilimumab and nivolumab (10 of 176, 5.68%) being the most common, and single agent nivolumab (9 of 222, 4.05%) and pembrolizumab (8 of 271, 2.95%) being slightly less frequent. By class PD-1 inhibitors were the most common treatment associated (n=18, 3.76%), however there was no one specific class more significantly associated with increased rates of encephalitis when comparing this to inhibitors of PD-L1 (n=2, 1.16%), CTLA-4 (n=2, 5.00%), or combination of PD-1/CTLA-4 (n=10, 6.02%) (p=0.26). Patients were treated with discontinuation of the therapy alone (n=7), high dose steroids alone (n=10), or a combination of high dose steroids, IVIG, or plasma exchange (n=15). The effects were typically reversible or non-disabling with the average 90-day ECOG score being 1.8. There were 8 patients (25%) who developed severe debility (n=4) or death (n=4). CONCLUSION Encephalitis is a rare complication associated with ICI therapies. Overall, there was no apparent specific drug or class more at risk of causing this complication. As ICI therapy is used more in practice, we will likely see a greater number of cases of ICI encephalitis and need to be aware of how it presents, diagnose, and treat appropriately to avoid permanent disability.

scholarly journals Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1448
Author(s):  
Raquel Herranz ◽  
Julia Oto ◽  
Emma Plana ◽  
Álvaro Fernández-Pardo ◽  
Fernando Cana ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Specific Treatment ◽  
Predictive Biomarkers ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Specific Patient ◽  
Free Dna ◽  
Potential Biomarker ◽  
Cancer Types

Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.

scholarly journals Immune-Related Meningoencephalitis following Nivolumab in Metastatic Renal Cell Carcinoma

2021 ◽  
pp. 1051-1058
Author(s):  
Lisa B.E. Shields ◽  
Mohammad S. Alsorogi ◽  
Nataliya Mar ◽  
Arash Rezazadeh Kalebasty
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Rare Complication ◽  
Psoas Muscle ◽  
High Dose ◽  
Lower Extremity Weakness ◽  
Left Psoas Muscle ◽  
Metastatic Rcc

While immunotherapy with nivolumab is promising for patients with renal cell carcinoma (RCC), overactivation of the immune system can lead to serious side effects. Immune-related meningoencephalitis without a viral or microbial etiology is a rare complication that may occur in patients treated with checkpoint inhibitors (CPI). Herein, we report a 66-year-old man who underwent a partial nephrectomy which revealed a papillary RCC with clear cell component. Three years later, an abdomen and pelvic CT revealed metastatic lesions in the left psoas muscle and in the left 12th rib. The patient was treated with pazopanib which was discontinued after 2 weeks due to significant hepatic and renal toxicity. He subsequently started sunitinib. Two months later, a chest, abdomen, and pelvic CT demonstrated progressive metastatic RCC in the retroperitoneal mass of the left psoas muscle and paraspinal musculature as well as a left renal mass. The patient was treated with 7 cycles of the CPI nivolumab. He was subsequently hospitalized for 3 weeks after experiencing bilateral lower extremity weakness, lethargy, several falls, hyperthermia, confusion, and gait abnormalities. A CSF analysis demonstrated a lymphocyte pleocytosis with elevated protein and no bacterial or viral growth. The patient was treated with high-dose steroids after which his symptoms resolved. Chest, abdomen, and pelvic CT scans over the next 3 years revealed no evidence of metastatic disease, reflecting a progression-free survival of 40 months. We highlight the unique case of a patient with metastatic RCC who experienced immune-related meningoencephalitis following immunotherapy with nivolumab. Medical oncologists should be alert to the potential development of immune-related encephalitis in patients treated with nivolumab and should promptly diagnose and treat this concerning condition. The excellent oncologic outcome of this case emphasizes the need for continued aggressive measures for management of CNS toxicity resulting from CPI therapy.

Bing-Neel syndrome: A case reports

2020 ◽  
pp. 107815522098342
Author(s):  
Sinan Demircioğlu ◽  
Pembe Oltulu ◽  
Ganime D Emlik ◽  
Atakan Tekinalp ◽  
Özcan Çeneli
Keyword(s):  
Kinase Inhibitor ◽  
Case Reports ◽  
Rare Complication ◽  
Brain Biopsy ◽  
High Dose ◽  
Waldenström Macroglobulinemia ◽  
Dose Methotrexate ◽  
Waldenstrom Macroglobulinemia ◽  
Bruton Tyrosine Kinase ◽  
Methotrexate Treatment

Introduction Bing-Neel syndrome (BNS) is a rare complication of of Waldenström macroglobulinemia (WM) identified by involvement of central nervous system (CNS) lymphoplasmacytic cells. Case report We present a patient who was diagnosed with Bing-Neel syndrome four years after the diagnosis of Waldenström macroglobulinemia. Management & outcome The patient was admitted with neurological symptoms. There were lesions associated with WM involvement on brain imaging. The diagnosis was made by brain biopsy. High dose methotrexate treatment was given. Discussion CNS infiltrating agents such as fludarabine, methotrexate and cytarabine are often used in BNS treatment. Ibrutinib, which is a new bruton tyrosine kinase inhibitor, has recently started to be used in BNS treatment, as it has been shown to be effective and penetrate the CNS.

scholarly journals Clinical presentation and immunological features of Post-Malaria Neurologic Syndrome: a case report and review of literature

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Nadia Castaldo ◽  
Carlo Tascini ◽  
Paola Della Siega ◽  
Maddalena Peghin ◽  
Davide Pecori
Keyword(s):  
Unmet Need ◽  
Specific Treatment ◽  
Rare Condition ◽  
Acute Disseminated Encephalomyelitis ◽  
Intravenous Immunoglobulins ◽  
Neurological Involvement ◽  
Systematic Research ◽  
High Dose ◽  
Microbiological Analysis ◽  
Randomized Controlled Studies

Abstract Background Malaria still represents a major health threat, in terms of both morbidity and mortality. Complications of malaria present a diversified clinical spectrum, with neurological involvement leading to the most serious related-conditions. The authors recently encountered a case of a 60-year old Italian man presenting with confusion, language disturbances and Parkinson-like syndrome 3 weeks after complete remission from severe Plasmodium falciparum cerebral malaria. Chemical and microbiological analysis revealed aseptic meningitis, diffuse encephalitis and abnormal immune-activation. Re-infection and recrudescence of infection were excluded. Further analysis excluded paraneoplastic and autoimmune causes of encephalitis. A diagnosis of Post-Malaria Neurological Syndrome (PMNS) was finally formulated and successfully treated with high dose of steroids. Methods A systematic research of current literature related to PMNS was performed. Results 151 cases of PMNS were included, the majority of which occurred after severe P. falciparum infections. Four main clinical pattern were identified: 37% of the cases presented as “classical” PMNS, 36% presented as delayed cerebellar ataxia (DCA), 18% resembled acute inflammatory demyelinating polyneuropathy (AIDP), and 8% presented as acute disseminated encephalomyelitis (ADEM)-like form. Differentiation between different forms was not always simple, as clinical and radiological findings frequently overlap. Overall, in almost all of the tested cases, cerebrospinal fluid was found pathological; EEG revealed nonspecific encephalopathy in 30% of classical PMNS and 67% ADEM; imaging tests were found abnormal in 92% of ADEM-like forms. Pathogenesis remains unclear. An autoimmune mechanism is the most corroborated pathogenic hypothesis. Overall, the majority of PMNS cases revert without specific treatment. In most severe forms, high dose steroids, intravenous immunoglobulins, and plasmapheresis have been shown to improve symptoms. Conclusions PMNS is a disabling complication of malaria. The overall incidence is not known, due to frequent misdiagnosis and under-reporting. Pathogenesis is not also fully understood, but rapid response to immune-modulating treatment along with similarities to auto-immune neurological disease, strongly support a dysregulated immunological genesis of this condition. The lack of randomized controlled studies regarding therapeutic approaches is a major unmet need in this setting. A systematic collection of all the PMNS cases would be desirable, in order to increase awareness of this rare condition and to prospectively investigate the most appropriate management.

Ranscriptome Analysis Reveals the Molecular Mechanism of Yiqi Rougan Decoction in Reducing CCl4-induced Liver Fibrosis in Rats

2021 ◽  
Author(s):  
Yu Xiong ◽  
Jinyuan Hu ◽  
Chen Xuan ◽  
Jiayu Tian ◽  
Kaiyue Tan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Molecular Mechanism ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
High Dose ◽  
Peroxisome Proliferator

Abstract BackgroundLiver fibrosis develops from various chronic liver diseases, and there is currently a lack of specific treatment strategies. Yiqi Rougan decoction (YQRG) is a traditional Chinese medicine that has shown durative effects in the treatment of liver fibrosis; however, the mechanism associated with YQRG-related improvements in liver fibrosis remains to be experimentally determined. This study evaluated the therapeutic effect of YQRG on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and its molecular mechanism. MethodsWe used low-, medium-, and high-dose YQRG to treat CCl4-induced liver fibrosis in rats, followed by assessment of liver injury and fibrosis according to liver appearance, body weight, liver mass index, histopathologic examination, and serum testing. Additionally, we performed transcriptome analysis using RNA-sequencing (RNA-seq) technology, including cluster, Gene Ontology (GO), and pathway analyses, to identify differentially expressed genes (DEGs), and protein and gene expression were detected by immunofluorescence (IFC), western blot, and real-time quantitative PCR. ResultsThe results showed that YQRG effectively alleviated CCl4-induced liver injury and fibrosis in rats, including observations of improved liver function, decreased activity of hepatic stellate cells (HSCs), and decreased extracellular matrix (ECM) deposition. Moreover, we identified downregulated and upregulated DEGs in the model group relative to the control and YQRG-treated groups, with GO analysis revealing their enrichment in biological processes, such as endoplasmic reticulum stress (ERS), apoptosis, and autophagy. Furthermore, pathway analysis showed that YQRG treatment downregulated the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/AKT) signalling pathways and upregulated other signalling pathways, including those related to peroxisome proliferator-activated receptors(PPAR) and AMP-activated protein kinase(AMPK), with these finding subsequently verified experimentally. ConclusionThese findings showed that YQRG improved CCl4-induced liver fibrosis through multiple mechanisms and pathways, offering critical insight into the YQRG-related therapeutic mechanism and promoting further research into its potential application.

A RARE ASSOCIATION OF CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY WITH ULCERATIVE COLITIS

2021 ◽  
pp. 18-19
Author(s):  
Nilima K. Shah ◽  
Ankita Patel ◽  
Umeshkumar Nakum ◽  
Ravindra Patel
Keyword(s):  
Ulcerative Colitis ◽  
Ulcerative Colitis Patient ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Rare Complication ◽  
Gastrointestinal Symptoms ◽  
Demyelinating Polyneuropathy ◽  
High Dose ◽  
Initial Symptom ◽  
Colitis Patient ◽  
Rare Association

Chronic inammatory demyelinating polyneuropathy (CIDP) is a rare complication of Ulcerative colitis and it is uncertain whether it is associated with Ulcerative colitis itself or with its treatment. We describe a case of CIDP-like neuropathy as an initial symptom of Ulcerative colitis. A 17 years old male patient presented with symmetrical weakness of both lower extremities with paresthesia of both hand and feet. With impression of AIDP patient was treated with plasmapheresis and discharged on tapering steroid therapy. After 3 months again presented with bilateral weakness of all four limbs associated with diarrhea and fever. Patient was diagnosed with Ulcerative colitis ,so considering previous episode as 1st episode of CIDP and with rare association with Ulcerative colitis . Patient was treated with high dose of steroids and immunosuppressive therapy. Neurological and gastrointestinal symptoms remarkably improved after treatment.

scholarly journals When steroids are not enough in immune-related hepatitis: current clinical challenges discussed on the basis of a case report

2020 ◽  
Vol 8 (2) ◽  
pp. e001322 ◽  
Author(s):  
Dimitrios C Ziogas ◽  
Aikaterini Gkoufa ◽  
Evangelos Cholongitas ◽  
Panagiotis Diamantopoulos ◽  
Amalia Anastasopoulou ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Liver Toxicity ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Phase Iii ◽  
Steroid Resistant ◽  
Immune Mediated ◽  
Cancer Types ◽  
Clinical Considerations ◽  
Steroid Refractory

Unleashing adaptive immunity via immune checkpoint inhibitors (ICPIs) in many cancer types led to durable antitumor responses and prolonged survivals and also added some new immune-related adverse events (irAEs) to the ‘old-fashioned’ safety profile of chemotherapy. Among bowel and endocrine irAEs, immune-mediated hepatotoxicity/hepatitis is a less common and far less well-studied toxicity, which, however, could develop into a serious complication, especially when it becomes persistent or refractory to steroids. Its incidence, onset and severity vary widely, depending on the type of underlying treated cancer, the class, the dosage and the duration of immunotherapy as well as the way of its administration (as a single agent or in combination with other ICPI or chemotherapy). In this study, we present a patient with metastatic melanoma who developed severe steroid-resistant ir-hepatitis after treatment with ipilimumab and required triple concurrent immunosuppression with prednisolone, mycofenolate mofetil and tacrolimus in order for his liver toxicity to be resolved. Intrigued by this case, we focused further on melanoma, as the disease-paradigm of immunotherapy in cancer, reviewed the reported incidence of hepatotoxicity among phase III ICPIs-containing trials on melanoma and discussed the main clinical considerations regarding the diagnosis and the management of persistent/steroid-refractory ir-hepatitis. As more clinical experience is gradually gained on this challenging topic, better answers are provided to questions about the appropriate diagnostic workup, the necessity of liver biopsy, the available immunosuppressive options beyond corticosteroids (their combinations and/or their sequence) as well as the correct decision on withdrawing or resuming immunotherapy. Nonetheless, a thorough multidisciplinary discussion is still required to individualize the overall approach in each case after failure of steroids.

Response to salvage therapy and survival after relapse in acute myelogenous leukemia.

1989 ◽  
Vol 7 (8) ◽  
pp. 1071-1080 ◽  
Author(s):  
M J Keating ◽  
H Kantarjian ◽  
T L Smith ◽  
E Estey ◽  
R Walters ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Acute Myelogenous Leukemia ◽  
Specific Treatment ◽  
Lactic Dehydrogenase ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Salvage Regimen ◽  
Conventional Dose ◽  
Acute Myelogenous ◽  
Probability Of Response

The response to and survival following first salvage therapy regimens for 243 patients with acute myelogenous leukemia (AML) treated between 1974 and 1985 were evaluated. Eighty (33%) patients obtained a complete remission (CR), 24% died prior to achieving a response, and 43% were resistant on their first salvage regimen. The median survival was 18 weeks. Five percent overall and 16% of the CR patients are predicted to survive for more than 5 years. The factor most strongly associated with response and survival was the duration of the initial remission with 49 of 82 (60%) patients whose initial CR duration was at least 1 year in duration obtaining a second CR v 31 of 161 (19%) for patients with a shorter remission (P less than .01). Age, liver function, serum lactic dehydrogenase (LDH), karyotype, and the proportion of blasts plus promyelocytes present at the time of starting salvage therapy were strongly associated with probability of response and survival. Multivariate analysis was used to develop logistic regression and proportional hazard models to predict probability of response and survival, respectively. The major regimens used were conventional-dose cytarabine (ara-C) (combined with anthracyclines or amsacrine), high-dose ara-C, rubidazone, amsacrine (AMSA), other anthracyclines, and autologous or allogeneic transplant programs. After allowing for the prognostic factors in the models, specific treatment regimens were not strongly associated with prognosis.

Sign in / Sign up

Export Citation Format

Share Document