Therapy in RCDII: Rationale for Combination Strategies?

2015 ◽  
Vol 33 (2) ◽  
pp. 227-230 ◽  
Author(s):  
Petula Nijeboer ◽  
Georgia Malamut ◽  
Gerd Bouma ◽  
Nadine Cerf-Bensussan ◽  
Frits Koning ◽  
...  
Keyword(s):  
High Risk ◽  
Malignant Transformation ◽  
Cell Lymphoma ◽  
Villous Atrophy ◽  
Topical Steroid ◽  
Signs And Symptoms ◽  
Low Grade ◽  
Combination Strategies ◽  
Negative Cell ◽  
Epithelial Lymphocyte

Refractory coeliac disease type II (RCDII) is characterized by a continuous gluten-independent duodenal immune activation with an extremely high risk of malignant transformation. It is therefore considered as an indolent lymphoma. RCDII is characterized by the presence of villous atrophy (Marsh III A-C) in combination with an aberrant intra- epithelial lymphocyte (IEL) population consisting of >20% sCD3-CD7+iCD3+ IELs. The sCD3-CD7+iCD3+ IELs are a heterogeneous lineage-negative cell population, consisting of cells that do or do not express CD127/IL7Rα. Experiments using IEL from non-RCDII patients have indicated that while the CD127- cells are IL-15 responsive, the CD127+ cells are not. Together with the observation that some patients express an aberrant (monoclonal) TCRγδ phenotype, this confirms the heterogeneity of the aberrant IEL population in RCDII and suggests that the aberrant cells are heterogeneous with respect to their response to common γ-chain cytokines. Although cladribine with or without autologous stem cell transplantation is effective in the treatment of signs and symptoms of RCDII and improves survival as compared to symptomatic topical steroid therapy, cladribine failures still bear a high risk of malignant transformation, and the rate of enteropathy-associated T-cell lymphoma (EATL) development in this subgroup is extremely high. It might be hypothesized that the heterogenous nature of aberrant IEL and the high risk of malignant transformation require a treatment strategy which is effective despite this heterogeneity. RCDII should be seen more in the light of a low-grade/no mass lymphoma or pre-EATL. We would suggest an upfront combination therapy approach integrating inhibition of downstream Jak-STAT signalling pathways with conventional therapy (2-CDA) to hopefully effectively treat signs and symptoms of RCDII and accomplish a more effective EATL prevention.

scholarly journals Multi Omics Profiling and Clustering Low Grade Glioma Based on Integrated Stress Status

2021 ◽  
Author(s):  
Xiaolin Ren ◽  
Xin Chen ◽  
Chen Zhu ◽  
Anhua Wu
Keyword(s):  
Stress Response ◽  
High Risk ◽  
Malignant Transformation ◽  
Immune Cell ◽  
High Risk Group ◽  
Low Grade Glioma ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Integrated Stress Response ◽  
Genome Atlas

Abstract Background: Although the prognosis of low-grade glioma (LGG) is better than that of glioblastoma (GBM), there are still some patients who will develop into high-grade glioma. Integrated stress response contributed to the malignant transformation of tumor. As there is few research focus on the integrated stress status in LGG, it is urgent to profile and re-classify LGG based on integrated stress response (ISR). Methods: Glioma patients were obtained from the Chinese Glioma Genome Atlas ( the Cancer Genome Atlas (TCGA) and GSE16011 cohorts. Statistical 8 analyses were conducted by GraphPad Prism and R language. Results: We quantified four types of integrated stress response respectively. The relationship between the four stress states and the clinical characteristics of LGG was analyzed. Then we re-classified the patients based on these four scores, we found that cluster 1 had the worst prognosis, whereby cluster 3 had the best prognosis. We also established an accurate ISR risk signature to predicting cluster 1. We found that immune response and suppressive immune cell components were more enriched in the high-risk group. We also profiled the genomic difference between low and high risk groups, including the non-missense mutation of drivel genes and the condition of copy number variation (CNV). Conclusion: LGG patients could be divided into four clusters based on the integrated stress status, cluster 1 exhibited malignant transformation trends. ISR signature could reflect the traits of cluster 1 well, high ISR score indicated worse prognosis and enriched inhibitory immune microenvironments.

Benefit of Rituximab Addition to High-Dose Programs with Autograft for B-Cell Lymphoma: A Multicenter GITIL Survey on 957 Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 207-207 ◽  
Author(s):  
Corrado Tarella ◽  
Manuela Zanni ◽  
Michele Magni ◽  
Fabio Benedetti ◽  
Tiziano Barbui ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Low Grade ◽  
High Grade ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Prognostic Features

Abstract Background: The outcome of B-cell lymphoma has definitely improved since the introduction of the anti-CD20 Rituximab, which can be effectively combined into conventional chemotherapy regimens. Rituximab can also be added to high-dose chemotherapy programs with autograft. However, the clinical benefit of combining Rituximab and autograft-based programs has not been proved yet. This issue is addressed in the present study. Patients and Methods: Data have been retrospectively collected on 957 B-cell lymphoma patients receiving a high-dose sequential (HDS) chemotherapy program, at 10 Italian Centers associated to GITIL (Gruppo Italiano Terapie Innovative nei Linfomi). Although the HDS schedule has been introduced almost 20 yrs. ago, most patients were treated in the last decade. They received most frequently either the HDS scheme adapted for follicular lymphoma (Tarella C et al. Leukemia 2000) or the hd-Ara-C-supplemented scheme developed for mantle-cell and diffuse large cell lymphoma (Magni M et al, Blood 2000; Cuttica A et al., Cancer 2003); overall, Rituximab was added to HDS (R+) in 483 (50.5%) patients, the remaining 474 (49.5%) received Rituximab-free HDS (R−). All patients entered the HDS-protocols due to high-risk prognostic features, their median age was 49 yrs. (range 17–70). The series included 403 patients (232 R+) with low-grade and 554 (251 R+) with intermediate/high grade B-cell lymphoma subtypes; HDS was delivered to 542 (259 R+) patients at diagnosis and to 415 (224 R+) at first or subsequent relapse. Results: at a median follow-up of 5 yrs, the 5-yr Overall Survival (OS) and Event-free Survival (EFS) projections were 66% and 55%, respectively, with a significantly better outcome for patients treated at diagnosis (5-yr OS: 72%, EFS: 61%) compared to patients at relapse (5-yr OS: 56%, EFS: 45%). In all instances, Rituximab addition was associated with significant improvements; in particular, the 5-yr EFS projections were:patients at diagnosis: 68% for R+ vs. 57% for R−;patients at relapse: 59% for R+ vs. 34% for R−;low-grade subtypes: 65% for R+ vs. 41% for R− (Figure 1A);intermediate/high-grade subtypes: 64% for R+ vs. 52% for R− (Figure 1B). In the Cox multivariate survival analysis, two factors had a significant impact on the EFS, i.e. relapse status at HDS (HR: 1.74, c.i.: 1.43–2.13) and Rituximab addition to HDS (HR: 0.60, c.i.: 0.49–0.75). Conclusions: the addition of Rituximab to high-dose programs with autograft may improve response and long-term outcome in high-risk B-cell lymphoma patients. Figure 1. EFS according to Rituximab [R] administration, in (A) low-grade and (B) intermediate/high-grade, B-cell lymphoma patients treated with a HDS program Figure 1. EFS according to Rituximab [R] administration, in (A) low-grade and (B) intermediate/high-grade, B-cell lymphoma patients treated with a HDS program

scholarly journals TissueCypher Barrett’s esophagus assay impacts clinical decisions in the management of patients with Barrett’s esophagus

2021 ◽  
Vol 09 (03) ◽  
pp. E348-E355
Author(s):  
David L. Diehl ◽  
Harshit S. Khara ◽  
Nasir Akhtar ◽  
Rebecca J. Critchley-Thorne
Keyword(s):  
High Risk ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Clinical Decision Making ◽  
Eradication Therapy ◽  
Low Risk ◽  
Management Approach ◽  
Low Grade ◽  
Management Decisions ◽  
The Impact

Abstract Background and study aims The TissueCypher Barrett’s Esophagus Assay is a novel tissue biomarker test, and has been validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). The aim of this study was to evaluate the impact of TissueCypher on clinical decision-making in the management of BE. Patients and methods TissueCypher was ordered for 60 patients with non-dysplastic (ND, n = 18) BE, indefinite for dysplasia (IND, n = 25), and low-grade dysplasia (LGD, n = 17). TissueCypher reports a risk class (low, intermediate or high) for progression to HGD or EAC within 5 years. The impact of the test results on BE management decisions was assessed. Results Fifty-two of 60 patients were male, mean age 65.2 ± 11.8, and 43 of 60 had long segment BE. TissueCypher results impacted 55.0 % of management decisions. In 21.7 % of patients, the test upstaged the management approach, resulting in endoscopic eradication therapy (EET) or shorter surveillance interval. The test downstaged the management approach in 33.4 % of patients, leading to surveillance rather than EET. In the subset of patients whose management plan was changed, upstaging was associated with a high-risk TissueCypher result, and downstaging was associated with a low-risk result (P < 0.0001). Conclusions TissueCypher was used as an adjunct to support a surveillance-only approach in 33.4 % of patients. Upstaging occurred in 21.7 % of patients, leading to therapeutic intervention or increased surveillance. These results indicate that the TissueCypher test may enable physicians to target EET for TissueCypher high-risk BE patients, while reducing unnecessary procedures in TissueCypher low-risk patients.

scholarly journals Sickle Cell Anemia Presenting with Vaso-Occlusive Pain: Should We Screen for COVID-19?

2021 ◽  
pp. 1-4
Author(s):  
Mohammad Ali ◽  
Lina Okar ◽  
Nabil E. Omar ◽  
Jabeed Parengal ◽  
Ashraf Soliman ◽  
...  
Keyword(s):  
High Risk ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Signs And Symptoms ◽  
Risk Groups ◽  
Position Statement ◽  
Interesting Case ◽  
International Federation ◽  
Cell Disease ◽  
The World

Despite the widespread of coronavirus disease-19 (CO­VID-19) infection around the world, there are very scarce reported literature about the care of patients with a known diagnosis of hemoglobin disorders such as sickle cell disease (SCD) or thalassemia and confirmed COVID-19 infection. Thalassemia International Federation issued a position statement to include patients with thalassemia and SCD among the high-risk groups of patients. Here, we present an interesting case of a 42-year-old patient know to have SCD presenting with Vaso-occlusive (VOC) pain episode in the absence of COVID-19 signs and symptoms, who tested positive for COVID-19 infection and had a smooth recovery. This case highlights the importance of screening SCD patients presenting with VOC-related events even in the absence of COVID-19 signs and symptoms.

scholarly journals RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii194-ii194
Author(s):  
Ingo Mellinghoff ◽  
Martin van den Bent ◽  
Jennifer Clarke ◽  
Elizabeth Maher ◽  
Katherine Peters ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Escalation ◽  
Objective Response ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
High Risk Population ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

scholarly journals HIGH‐RISK MANTLE CELL LYMPHOMA IN THE LYMA TRIAL: A LYSA STUDY

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
M. Cheminant ◽  
B. Burroni ◽  
Y. Bris ◽  
L. Chartier ◽  
L. Oberic ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Mantle Cell
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