The Use of Gene-Expression Profiling to Predict Outcome of Follicular Lymphoma Patients Treated with Rituximab and Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1395-1395
Author(s):  
Antti Harjunpää ◽  
Matti Nykter ◽  
Outi Monni ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Samuli Hemmer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Follicular Lymphoma ◽  
Expression Patterns ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Feature Selection Method ◽  
Risk Groups ◽  
Gene Predictor ◽  
Anti Cd20

Abstract The anti-CD20 monoclonal antibody rituximab has been extensively evaluated for treatment of follicular lymphoma (FL) and is now an integral component of many treatment strategies. However, it is not known when and how to use this combination modality best in the overall treatment course of FL patients. Here we have analyzed the pattern of gene expression in lymph nodes from 28 FL patients who received rituximab in combination with chemotherapy. We demonstrate a novel feature selection method, in which genes whose expression correlates with treatment outcome are devided into groups based on similar expression patterns. By selecting representatives from these groups we built a three-gene predictor (for example RRAD, MGC5254, MARCO) which turned out to be successful in classifying all 28 samples correctly with respect to the responders versus nonresponders distinction. A similar four-gene predictor (for example USP9Y, CUL-4B, NSFS/REST, MADH) correctly classified the responding patients into two subgroups with very different event-free survival rates at the median follow up of 21 months (median not reached vs. 15 months, p<0.0001). The latter predictor also efficiently delineated patients within specific FLIPI risk groups. Our data demonstrate the ability of these microarray-based predictors to classify FL patients treated with rituximab and chemotherapy to subgroups with significantly distinct outcomes.

scholarly journals NOVEL DRUGS IN FOLLICULAR LYMPHOMA

2016 ◽  
Vol 8 ◽  
pp. 2016061 ◽  
Author(s):  
Giuseppe Rossi ◽  
Antonella Anastasia
Keyword(s):  
Follicular Lymphoma ◽  
Treatment Strategies ◽  
Cell Receptor ◽  
Phase Iii ◽  
Non Hodgkin Lymphoma ◽  
Free Treatment ◽  
Phase Iii Trials ◽  
New Treatment ◽  
Anti Cd20 ◽  
Key Steps

Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of a chieving a definite cure, have prompted investigations into the possible role of more effective and less toxic strategies with innovative therapeutic agents.  Recently Casulo et al demonstrated that approximately 20% of patients with FL actually relapse within 2 years after achieving remission with R-CHOP and have a poor prognosis. It is conceivable that this particularly chemoresistant population would benefit from specifically targeting the biologic and genetic factors that likely contribute to their poor prognosis.Evolving strategies for difficult to treat FL patients have recently considered  immunomodulatory agents, new monoclonal antibodies as well as drugs targeting selective intracellular pathways. The importance of targeting the microenvironment together with the malignant FL cell has been particularly underscored. We review the most promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs (Lenalidomide), with mAbs directed against other surface antigens such as CD22 and CD23 (epratuzumab, lumiliximab), with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling such as PI3K inibithors(idelalisib, duvelisib). Another highly attractive approach is the application of the bi-specific T-cell engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens. Moreover, we highlight the potential of these therapies,  taking into account their toxicity. Of course we must wait for Phase III trials results to confirm the benefit of these new treatment strategies toward a new era of chemotherapy-free treatment for follicular lymphoma.

scholarly journals Development and validation of a 13-m6a related lncRNA prognostic signature for lung adenocarcinoma

2021 ◽  
Author(s):  
Pingfan Wu ◽  
Xiaowen Zhao ◽  
Ling Xue ◽  
Xiaojing Yang ◽  
Yuxiang Shi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Adenocarcinoma ◽  
Treatment Strategies ◽  
Risk Groups ◽  
Gene Expression Omnibus ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
P53 Signaling ◽  
Selection Operator

Abstract Considerable evidence suggests that N6-methyladenosine (m6A) is involved in the regulation of long non-coding RNA (lncRNA), whichparticipates in the occurrence, development and prognosis of tumorscancerBut the relationship between m6A regulators-related lncRNA (mRlncRNA) and lung adenocarcinoma (LUAD) remains unclear. This study aims to determine a feature based on mRlncRNA for prognostic evaluation of LUAD patients. By integrating the gene expression data of LUAD and normal samples from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, the m6A gene and mRlncRNA with imbalanced expression were screened out. Then we used the least absolute shrinkage and selection operator (LASSO) to obtain the 13-lncRNA prognostic signature in the TCGA training cohort. Patients were divided into two risk groups based on the risk score of lncRNAs characteristics, and their overall survival (OS) was significantly different. The predictive power of this signature was verified in TCGA testing cohort and entire TCGA cohort. These landmark lncRNAs were involved in several biologiocal processes and pathways related to cell cycle, DNA replication, P53 signaling pathway and mismatch repair. Besides, the high-risk group was low-response to cisplatin, while high-response to mitomycin, docetaxel and immunotherapy. In conclusion, we identified a 13-mRlncRNA model associated with prognosis and treatment sensitivity in LUAD, which may provide clues about the influence of m6A on lncRNA in LUAD and promote the further improvement of LUAD individualized treatment strategies.

scholarly journals Three Years Follow-Up Study Showed Prenatal Methamphetamine Exposure May Cause Chronic Abnormalities In Transcriptomic Pattern

2021 ◽  
Author(s):  
Arvin Haghighatfard ◽  
Soha Seifollahi ◽  
Pegah Rajabi ◽  
Niloofar Rahmani ◽  
Rojin Ghannadzadeh
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Childbearing Age ◽  
Methamphetamine Use ◽  
Methamphetamine Use Disorder

Abstract Background: The high rate of methamphetamine use disorder among young adults and women of childbearing age makes it imperative to clarify the long-term effects of Methamphetamine exposure on the offspring. Behavioral and cognitive problems had been reported in children with parental Methamphetamine exposure (PME). The present study aimed to assess the acute and chronic effects of PME in molecular regulations and gene expression profiles of children during their first years of life.Methods: All subjects were recruited before birth, and sampling was conducted from the first ten days of birth, twelve months, twenty months, and thirty-six months of age. Finally, 2658 children with PME and 3573 normal children had been finished the follow-up. RNA extraction was operated from blood samples and gene expression profiling was conducted by using the Affymetrix GeneChip Human Genome U133 plus 2.0 Array Platform. Gene expression data were confirmed by Real-time PCR. Results: Gene expression profiling during thirty-six months showed several constant mRNA level alterations in children with PME compared with normal. These genes are involved in several gene ontologies and pathways involved with the immune system, neuronal functions, and bioenergetic metabolism. It seems that Methamphetamine use disorder before and during the pregnancy period may affect the expression profile of children, and these changes could remain years after birth. Affected genes have some similarities with the gene expression patterns of addiction, psychiatric disorders, neurodevelopmental disabilities, and immune deficiencies. Conclusion: Findings may shed light on the molecular effects of prenatal methamphetamine exposure and may lead to new psychological and somatic caring protocols for these children based on their potential abnormalities.

Abstract 17402: Single Nuclei RNA-sequencing of Human Hypertrophic Cardiomyopathy Myectomy Samples Reveals Common Novel Mechanisms of Pathogenesis and Potential Therapeutic Targets Regardless of Genotype

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Amy Larson ◽  
Hassan Rastegar ◽  
Gordon S Huggins ◽  
Ethan J Rowin ◽  
Martin S Maron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hypertrophic Cardiomyopathy ◽  
Rna Sequencing ◽  
Alternative Treatment ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Surgical Myectomy

Introduction: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease, often resulting in left ventricular outflow tract obstruction, relieved by surgical myectomy. Current treatments are largely palliative and do not target the root causes. Understanding the molecular drivers of the disease could lead to alternative treatment strategies through identification of novel therapeutic targets. Methods: We performed single nuclei RNA-sequencing (snRNA-seq) on thousands of nuclei from 9 patient myectomy samples and septal tissue from 4 unused donor hearts selected randomly without regard to genotype to identify the cell populations and determine the gene expression patterns in individual cells. Each sample was processed individually using Seurat v3 for quality control and normalization. Next, all 13 samples were integrated into a combined dataset for clustering and differential gene expression analysis to identify markers specific to each cluster and to assign cell identities. Results: Our results revealed several clusters of cardiomyocytes with differences in sarcomeric and metabolic gene expression. Several fibroblast populations were also observed. Numerous genes were differentially expressed between the HCM and normal samples. For example, RARRES1 expression was observed in many of the fibroblast populations in the normal samples, but was absent in the HCM samples. RARRES1 is involved in regulating fatty acid metabolism and autophagy, both of which are altered in HCM. Additionally, expression of PLA2G2A was absent in the HCM samples but was present in almost every cell type in the normal controls. PLA2G2A is involved in suppression of RTK mediated hypertrophic signaling, impacts lipid signaling, and has tumor suppressor properties. Thus, both RARRES1 and PLA2G2A may represent novel targets in HCM. Conclusions: This approach reveals novel potential therapeutic targets within common final HCM pathological pathways independent of genotype that have the potential to guide development of alternative treatment strategies. Further analysis of larger datasets using this approach will likely identify even more common pathway targets and identify additional common mechanisms in the pathogenesis of obstructive HCM.

scholarly journals Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab

Blood ◽  
2008 ◽  
Vol 111 (12) ◽  
pp. 5530-5536 ◽  
Author(s):  
Issa F. Khouri ◽  
Peter McLaughlin ◽  
Rima M. Saliba ◽  
Chitra Hosing ◽  
Martin Korbling ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Nonmyeloablative Stem Cell Transplantation

Abstract Nonmyeloablative stem cell transplantation in patients with follicular lymphoma has been designed to exploit the graft-versus-lymphoma immunity. The long-term effectiveness and toxicity of this strategy, however, is unknown. In this prospective study, we analyzed our 8-year experience. Patients received a conditioning regimen of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days), and rituximab (375 mg/m2 for 1 day plus 1000 mg/m2 for 3 days). They were then given an infusion of human leukocyte antigen-matched hematopoietic cells from related (n = 45) or unrelated donors (n = 2). Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Forty-seven patients were included. All patients experienced complete remission, with only 2 relapses. With a median follow-up time of 60 months (range, 19-94), the estimated survival and progression-free survival rates were 85% and 83%, respectively. All 18 patients who were tested and had evidence of JH/bcl-2 fusion transcripts in the bone marrow at study entry experienced continuous molecular remission. The incidence of grade 2-IV acute GVHD was 11%. Only 5 patients were still undergoing immunosuppressive therapy at the time of last follow-up. We believe that the described results are a step forward toward developing a curative strategy for recurrent follicular lymphoma.

The clinical value and the cost-effectiveness of follow-up in endometrial cancer patients

2004 ◽  
Vol 14 (5) ◽  
pp. 931-937 ◽  
Author(s):  
W. A. A. Tjalma ◽  
P. A. Van Dam ◽  
A. P. Makar ◽  
D. J. Cruickshank
Keyword(s):  
Endometrial Cancer ◽  
Cost Effectiveness ◽  
Cancer Patients ◽  
Survival Rates ◽  
Risk Groups ◽  
Evidence Base ◽  
Clinical Value ◽  
The Times ◽  
The Cost

The aim of the present article was to evaluate the cost-effectiveness of follow-up in endometrial cancer patients. A literature review was performed regarding the studies that addressed routine follow-up of endometrial cancer. For each published study, the costs of the follow-up program were calculated according to Belgium standards. A mean total of 13% relapsed. Symptomatology and clinical examination detected over 83% of the recurrences. The follow-up cost in euro after 5 and 10 years ranged between 127.68 and 2028.78 and between 207.48 and 2353.48, respectively. Based on the available data, there is little evidence of routine follow-up improving survival rates. Multiple protocols are used in practice without an evidence base. There is an urgent need for prospective randomized studies to evaluate the value of the current so-called ‘standard medical practice of follow-up.’ It is to be expected that the cost of follow-up could be reduced considerably, for instance, by tailoring to low- and high-risk groups, or by abandoning routine follow-up. Symptomatic patients, however, should be evaluated immediately. A reduction in the number of visits and examinations would mean an enormous reduction in costs. This economic benefit would be warmly welcomed in the times of increased health costs and decreased budgets.

Primary Follicular Lymphoma of the Duodenum Is a Distinct Mucosal/Submucosal Variant of Follicular Lymphoma: A Retrospective Study of 63 Cases

2011 ◽  
Vol 29 (11) ◽  
pp. 1445-1451 ◽  
Author(s):  
Ana-Iris Schmatz ◽  
Berthold Streubel ◽  
Elisabeth Kretschmer-Chott ◽  
Andreas Püspök ◽  
Ulrich Jäger ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Stable Disease ◽  
Cell Transformation ◽  
Large Cell ◽  
Low Grade ◽  
Complete Regression ◽  
Watch And Wait ◽  
Small Series ◽  
Anti Cd20

Purpose Small series with limited follow-up have suggested primary follicular lymphoma of the duodenum (FL-D) to be an indolent disease. We report our experience on a large series of patients followed for a median time period of longer than 6 years. Patients and Methods The study comprised 63 patients with primary FL-D defined as stage I disease. Endoscopy and detailed pathologic work-up was performed at diagnosis and at restaging to monitor the behavior of the neoplastic process. Results Histologically, all 63 patients had FL, low grade (1 to 2). Duodenal endosonography demonstrated lesions confined to mucosa/submucosa in 19 of 20 patients. At an overall median follow-up of 77 months (range, 12 to 177 months), only two untreated patients had developed nodal disease, the remaining 61 patients never experienced extrasmall intestinal disease and large cell transformation did not occur at all. Among 24 patients followed by watch and wait strategy, seven showed spontaneous complete regression and 17 had stable disease; radiotherapy resulted in complete regression in all 19 patients; anti-CD20 antibody monotherapy achieved complete regression in four patients and stable disease in one patient. Various chemotherapy protocols in eight patients caused complete regression in all of them, but local relapses occurred in three. No patients required surgery or died of disease. Conclusion These findings characterize primary FL-D as a remarkably indolent FL variant, which, even left untreated, does not develop tumorous growth, very rarely disseminates (two of 63 patients) and does not transform to high grade disease. A watch and wait approach appears to be the most sensible strategy.

R-FND Followed by Radioimmunotherapy for High-Risk Follicular Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3056-3056 ◽  
Author(s):  
Peter McLaughlin ◽  
Sattva Neelapu ◽  
Michelle Fanale ◽  
Maria Rodriguez ◽  
Ana Ayala ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Ibritumomab Tiuxetan ◽  
Free Survival ◽  
Grade 3 ◽  
Anti Cd20 ◽  
Better Than

Abstract Follicular lymphoma (FL) patients, (pts) with high-risk features using the FL International Prognostic Index (FLIPI) have an expected 5-year survival of only about 50% with conventional therapy. With the incorporation of anti-CD20 monoclonal antibody (mAb) therapy, results are improving (e.g., Buske, Blood2006; 108: 1504). Starting in 2003, we have treated high-risk (FLIPI ≥3) FL pts with R-FND (rituximab, fludarabine, mitoxantrone, dexamethasone) for 4 cycles, followed by radioimmunotherapy (RIT) with ibritumomab tiuxetan, and subsequent rituximab maintenance. Results for the first 35 pts are: complete (CR) and partial (PR) remission 83% and 14%; 3-year overall (OS) and failure-free survival (FFS) 89% and 74% (median follow-up 24 mo.). RIT converted 5 PR pts to CR. Toxicity was mainly hematologic. Five pts did not receive RIT, one because of neutropenia after R-FND. Following RIT, platelet and neutrophil nadirs were 28 and 0.3, occurring at 4–7 weeks. 16 pts required transfusions, and 27 received growth factors. 13 pts had infections, only 2 of which were grade 3. Recovery occurred by 3 weeks in most, with prolonged cytopenias in 6. There has been 1 case of myelodysplasia. In conclusion, the additional complexity of this RIT intensification strategy is warranted in this high-risk FL population, resulting in OS and FFS outcomes that are better than non-mAb therapies, and at least as good as published chemotherapy-rituximab combination therapy.

Combination Biologic Therapy as Initial Treatment for Follicular Lymphoma: Initial Results From CALGB 50701 - a Phase II Trial of Extended Induction Epratuzumab (anti-CD22) and Rituximab (anti-CD20)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 427-427 ◽  
Author(s):  
Barbara Grant ◽  
John P. Leonard ◽  
Jeffrey L Johnson ◽  
Lale Kostakoglu ◽  
Eric Hsi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Follicular Lymphoma ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Good Tolerability ◽  
Grade 3 ◽  
Anti Cd20

Abstract Abstract 427 Rituximab is effective as single agent therapy in the treatment of follicular lymphoma (FL), and when combined with chemotherapy has extended remissions and survival. Epratuzumab (Immunomedics), a humanized anti-CD22 monoclonal antibody, also has single agent activity in FL, and in combination with rituximab led to durable complete responses in the treatment of patients (pts) with relapsed and refractory indolent NHL. To evaluate the hypothesis that combining a second biological agent with rituximab might improve efficacy with good tolerability, the CALGB treated 60 previously untreated pts with epratuzumab and rituximab in a multicenter phase II trial and we report here the preliminary response and toxicity findings. Rituximab was administered at 375 mg/m2 iv weekly for four weeks, then every 8 weeks for four additional doses for a total of 8 doses over 9 months. Epratuzumab, was given at 360 mg/m2 two days before the first rituximab dose to assess toxicity. From week 2 on, epratuzumab was given before the rituximab on the same day for a total of 8 doses over 9 months. Fifty-seven evaluable pts were enrolled between May 2008 and September 2009. FLIPI scores at study entry were 13 (22%) low; 28 (47.5%) intermediate; and 18 (30.5%) high. Fifty-three pts completed all therapy through month 9. One pt was taken off therapy due to progression after month 5. One pt died during induction from line sepsis. Two pts were taken off study due to adverse events, 1 during induction (grade 4 thrombosis and MI), 1 following month 5 (dyspnea, hypoxia and pulmonary NOS). All other toxicities were grade 3 or lower, including fatigue (grade 3 3%, grade 2 17%), nodal pain (grade 3 5%, grade 2 8%), and cytokine release and pruritis (grade 2, 5% each). To date, there have been 19 CRs (33.3%), 29 PRs (50.9%)(ORR 84.2%); 9 (15.8%) had stable disease. All 19 CR patients completed all treatment. The mean time to CR was 9 months. Two patients progressed after a period of stable disease, and 25 of the 29 patients who achieved PR remain in response. All 19 CRs also remain in remission at this point with a median follow-up of 0.82 years (range 0.52 to 2.0). FLIPI score was not predictive of response. The CR rate in low risk pts was 31%, 44% in intermediate risk and 18% in high risk pts. There was a trend toward higher CR rate among patients with FcgR2A His (n=10, CR 60%) and to a lower CR rate among those with FcgR2A Arg (n=14, CR 14.3%). Correlations with PET scan at week 3, with tissue biomarkers and to statin use are being analyzed. Rituximab and epratuzumab is an effective and very well tolerated regimen with an ORR of 84% in previously untreated patients with follicular lymphoma. Disclosures: Off Label Use: Use of Epratuzumab, a humanized antiCD22 monoclonal antibody in treatment of follicular lymphoma. Leonard:BiogenIDEC: Consultancy; Genentech: Consultancy; Immunomedics: Consultancy. Jones:Glaxo Smith-Kline: Consultancy; Abbott: Research Funding. Cheson:Genentech: Consultancy.

scholarly journals Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results

Blood ◽  
2012 ◽  
Vol 119 (26) ◽  
pp. 6373-6378 ◽  
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
William D. Erwin ◽  
Barry I. Samuels ◽  
Martin Korbling ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
Low Frequency ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Ibritumomab Tiuxetan ◽  
Free Survival ◽  
Innovative Strategies

In 2008, we reported favorable 5-year outcomes of nonmyeloablative allogeneic stem cell transplantation after fludarabine, cyclophosphamide, rituximab (FCR) conditioning for relapsed and chemosensitive follicular lymphoma. However, innovative strategies were still needed to treat patients with chemorefractory disease. We therefore subsequently performed a trial in which 90Y-ibritumomab tiuxetan (0.4 mCi/kg) was added to the fludarabine, cyclophosphamide conditioning regimen (90YFC). Here, we report updated results of the FCR trial and outcomes after 90YFC. For the FCR group (N = 47), since the last update, one patient developed recurrent disease. With a median follow-up of 107 months (range, 72-142 months), the 11-year overall survival and progression-free survival rates were 78%, and 72%, respectively. For the 90YFC group (N = 26), more patients had chemorefractory disease than did those in the FCR group (38% and 0%, P < .001). With a median follow-up of 33 months (range,17-94 months), the 3-year progression-free survival rates for patients with chemorefractory and chemosensitive disease were 80% and 87%, respectively (P = .7). The low frequency of relapse observed after a long follow-up interval of 9 years in the FCR group suggests that these patients are cured of their disease. The addition of 90Y to the conditioning regimen appears to be effective in patients with chemorefractory disease. This trial was registered at www.clinicaltrials.gov as NCT00048737.

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