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Biomedical Journal Jun 2022Allograft rejection is one of the obstacles in achieving a successful vascularized composite allotransplantation (VCA). Treatments of graft rejection with lifelong... (Review)
Review
Allograft rejection is one of the obstacles in achieving a successful vascularized composite allotransplantation (VCA). Treatments of graft rejection with lifelong immunosuppression (IS) subject the recipients to a lifelong risk of cancer development and opportunistic infections. Cell therapy has recently emerged as a promising strategy to modulate the immune system, minimize immunosuppressant drug dosages, and induce allograft tolerance. In this review, the recent works regarding the use of cell therapy to improve allograft outcomes are discussed. The current data supports the safety of cell therapy. The suitable type of cell therapy in allotransplantation is clinically dependent. Bone marrow cell therapy is more suitable for the induction phase, while other cell therapies are more feasible in either the induction or maintenance phase, or for salvage of allograft rejection. Immune cell therapy focuses on modulating the immune response, whereas stem cells may have an additional role in promoting structural regenerations, such as nerve regeneration. Source, frequency, dosage, and route of cell therapy delivery are also dependent on the specific need in the clinical setting.
Topics: Cell- and Tissue-Based Therapy; Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Vascularized Composite Allotransplantation
PubMed: 35042019
DOI: 10.1016/j.bj.2022.01.005 -
Annals of Allergy, Asthma & Immunology... Oct 2023A "window of opportunity" has been proposed where anti-inflammatory therapy administration in response to symptoms could prevent exacerbation.
BACKGROUND
A "window of opportunity" has been proposed where anti-inflammatory therapy administration in response to symptoms could prevent exacerbation.
OBJECTIVE
To evaluate rescue and maintenance therapy claims surrounding a severe asthma exacerbation serious enough to require a face-to-face clinical encounter.
METHODS
Merative MarketScan research databases (US administrative claims 2011 to 2017) were analyzed for patients aged ≥4 years, with an asthma diagnosis code, who filled short-acting β-agonist (SABA) and Global Initiative for Asthma Steps 3 to 5 maintenance therapies. Patients were indexed on a random SABA claim and had 12 months' continuous health plan eligibility pre- and post-index. Serious exacerbations were severe exacerbations requiring systemic corticosteroids prescribed from an outpatient clinic, urgent care or emergency department, or hospitalization for asthma. SABA and maintenance claims 30 days pre- and post-event were analyzed.
RESULTS
Of 319,342 patients (30% children 4 to 11 years; 70% adults or adolescents ≥12 years), 27.2% of children and 16.8% of adolescents or adults experienced ≥ 1 serious exacerbation (unadjusted odds ratio [OR], 1.85 [95% confidence interval, 1.81-1.88]). In the 30 days pre-event, 42.6% filled ≥1 SABA (children: 44.3%; adolescents or adults: 41.5%; OR, 1.12 [1.09-1.16]) and 57.4% filled maintenance (children: 59.0%; adolescents or adults: 56.3%; OR, 1.12 [1.08-1.15]). In the 30 days post-event, 61.4% filled SABA (children: 69.7%; adolescents or adults: 55.6%; OR, 1.84 [1.78-1.90]) and 94.8% filled maintenance (children: 98.6%; adolescents or adults: 92.2%; OR, 6.09 [5.45-6.81]).
CONCLUSION
Many patients treated as having moderate-to-severe asthma escalate SABA claims before a serious exacerbation, but approximately 40% have no anti-inflammatory maintenance fill, highlighting a "window of opportunity" to prevent exacerbations using inhaled corticosteroids concomitantly with SABA as rescue.
Topics: Adult; Child; Adolescent; Humans; Anti-Asthmatic Agents; Asthma; Adrenal Cortex Hormones; Administration, Inhalation; Hospitalization
PubMed: 37343824
DOI: 10.1016/j.anai.2023.06.018 -
Annals of Nutrition & Metabolism 2016Oral immunotherapy (OIT) is a promising investigational therapy for food allergy. Clinical trials in peanut, milk, egg, and wheat allergy provide evidence that OIT can... (Review)
Review
Oral immunotherapy (OIT) is a promising investigational therapy for food allergy. Clinical trials in peanut, milk, egg, and wheat allergy provide evidence that OIT can effectively desensitize a majority of individuals to a food allergen. While a portion of subjects demonstrate sustained unresponsiveness, the majority regain sensitivity with allergen avoidance. The safety and tolerability of OIT continue to limit its use in some patients. Virtually all studies report adverse reactions that are more frequent during dose escalation but may also occur during maintenance therapy. Recent studies have identified adjunctive therapies (such as omalizumab) which may mitigate adverse effects. There is a paucity of data on the long-term safety and efficacy of OIT. Further study is required before OIT is ready for routine clinical practice. This review is intended to provide the reader with an up-to-date understanding of OIT, including its mechanisms, efficacy, safety profile, and potential utility in clinical practice.
Topics: Administration, Oral; Adult; Animals; Antigens; Child; Desensitization, Immunologic; Dietary Proteins; Evidence-Based Medicine; Food Hypersensitivity; Humans; Immune Tolerance; Immunotherapy; Precision Medicine; Quality of Life; Secondary Prevention
PubMed: 27355816
DOI: 10.1159/000445391 -
Journal of Hematology & Oncology Jul 2023The mRNA-based therapeutics have become the hot spot of biopharmaceutical industries in recent years. The landscape of this area is expanding from infectious disease to...
The mRNA-based therapeutics have become the hot spot of biopharmaceutical industries in recent years. The landscape of this area is expanding from infectious disease to cancer, which needs to be summarized to provide data supports for industries and research institutions. Based on the Trialtrove database, a total of 108 clinical trials from 1999 to 2021 were retrospectively analyzed. We have demonstrated that the clinical development of mRNA therapies against solid tumors is still at an early stage. There are evolutions in delivery systems from the dendritic cell to the lipid-based platform and in encoding strategies from the fixed tumor antigens to the personalized neoantigens. The adjuvant or maintenance therapy and the combination treatment with checkpoint inhibitors are becoming the major clinical development orientation.
Topics: Humans; RNA, Messenger; Retrospective Studies; Neoplasms; Antigens, Neoplasm; Immunotherapy; Cancer Vaccines
PubMed: 37464375
DOI: 10.1186/s13045-023-01457-x -
Biology of Blood and Marrow... Jul 2016Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT)... (Review)
Review
Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas.
Topics: Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Maintenance Chemotherapy; Salvage Therapy; Survival Analysis; Transplantation, Autologous; Treatment Outcome
PubMed: 26899562
DOI: 10.1016/j.bbmt.2016.02.007 -
Alimentary Pharmacology & Therapeutics Oct 2023Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat.
AIM
To assess the efficacy of medical treatments for UP.
METHODS
We searched MEDLINE, EMBASE, and CENTRAL on 23 November 2022 for randomised controlled trials (RCTs) of medical therapy for adults with UP. Primary outcomes included induction and maintenance of clinical remission. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome.
RESULTS
We included 53 RCTs (n = 4096) including 46 induction studies (n = 3731) and seven maintenance studies (n = 365). First-line therapies included topical 5-aminosalicylic acid (5-ASA), conventional corticosteroids, budesonide, and oral 5-ASA. Therapy for refractory UP included topical tacrolimus and small molecules. Topical 5-ASA was superior to placebo for induction (RR 2.72, 95% CI 1.94-3.82) and maintenance of remission (RR 2.09, 95% CI 1.26-3.46). Topical corticosteroids were superior to placebo for induction of remission (RR 2.83, 95% CI 1.62-4.92). Topical budesonide was superior to placebo for induction of remission (RR 2.34, 95% CI 1.44-3.81). Combination therapy with topical 5-ASA and topical corticosteroids was superior to topical monotherapy with either agent. Topical tacrolimus was superior to placebo. Etrasimod was superior to placebo for induction (RR 4.71, 95% CI 1.2-18.49) and maintenance of remission (RR 2.08, 95% CI 1.31-3.32).
CONCLUSIONS
Topical 5-ASA and corticosteroids are effective for active UP. Topical 5-ASA may be effective for maintenance of remission. Tacrolimus may be effective for induction of remission. Etrasimod may be effective for induction and for maintenance of remission. Trials should include UP to expand the evidence base for this under-represented population.
Topics: Adult; Humans; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Colitis, Ulcerative; Mesalamine; Proctitis; Remission Induction; Tacrolimus
PubMed: 37589498
DOI: 10.1111/apt.17666 -
International Journal of Molecular... Jun 2021Mitochondrial DNA depletion and multiple deletions syndromes (MDDS) constitute a group of mitochondrial diseases defined by dysfunctional mitochondrial DNA (mtDNA)... (Review)
Review
Mitochondrial DNA depletion and multiple deletions syndromes (MDDS) constitute a group of mitochondrial diseases defined by dysfunctional mitochondrial DNA (mtDNA) replication and maintenance. As is the case for many other mitochondrial diseases, the options for the treatment of these disorders are rather limited today. Some aggressive treatments such as liver transplantation or allogeneic stem cell transplantation are among the few available options for patients with some forms of MDDS. However, in recent years, significant advances in our knowledge of the biochemical pathomechanisms accounting for dysfunctional mtDNA replication have been achieved, which has opened new prospects for the treatment of these often fatal diseases. Current strategies under investigation to treat MDDS range from small molecule substrate enhancement approaches to more complex treatments, such as lentiviral or adenoassociated vector-mediated gene therapy. Some of these experimental therapies have already reached the clinical phase with very promising results, however, they are hampered by the fact that these are all rare disorders and so the patient recruitment potential for clinical trials is very limited.
Topics: Animals; Combined Modality Therapy; DNA Replication; DNA, Mitochondrial; Disease Management; Disease Susceptibility; Gene Expression Regulation; Humans; Mitochondria; Mitochondrial Diseases; Mitochondrial Proteins; Mutation
PubMed: 34208592
DOI: 10.3390/ijms22126447 -
American Society of Clinical Oncology... Apr 2022Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple...
Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple myeloma therapeutics has significantly changed over the last 2 decades, with disease remissions lasting much longer. The advent of modern-day induction regimens, usage of high-dose melphalan followed by autologous stem cell transplantation, and well-tolerated maintenance regimens has resulted in deeper and durable responses, with less frequent disease recurrences, and patients are living much longer. Moreover, the conventional testing for response assessments in multiple myeloma was developed at least 60 years earlier, and there was a clear need for more sensitive diagnostics to test measurable residual disease at deeper levels. Next-generation sequencing and next-generation flow cytometry are highly sensitive techniques that were refined over the last decade and have a sensitivity of 10 to 10 (1 cell per 100,000/1 million). More recently, immunotherapy strategies-including the cellular therapies-have allowed us to expand our ability to achieve and maintain measurable residual disease negativity even in the refractory setting. These advances have brought us much closer to a cure for multiple myeloma; clearly, it has become more realistically achievable, challenging the dogma of multiple myeloma as an incurable disease.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasm, Residual; Transplantation, Autologous
PubMed: 35623025
DOI: 10.1200/EDBK_349603 -
Current Opinion in Allergy and Clinical... Apr 2019Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring... (Review)
Review
PURPOSE OF REVIEW
Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring and a detailed multidisciplinary team assessment to identify modifiable factors contributing to poor control is needed prior to considering therapy escalation. Pathophysiological phenotyping in those with true severe therapy-resistant asthma (STRA) and the current array of add-on therapies will be discussed.
RECENT FINDINGS
Adherence monitoring using electronic devices has shown that only 20-30% of children with PSA have STRA and need additional therapies. Omalizumab and mepolizumab are licensed for children with STRA aged 6 years and older. Although robust safety and efficacy data, with reduced exacerbations, are available for omalizumab, biomarkers predicting response to treatment are lacking. Paediatric safety data are available for mepolizumab, but efficacy data are unknown for those aged 6-11 years and minimal for those 12 years and older. A sub-group of children with STRA have neutrophilia, but the clinical significance and contribution to disease severity remains uncertain.
SUMMARY
Most children with PSA have steroid sensitive disease which improves with adherence to maintenance inhaled corticosteroids. Add-on therapies are only needed for the minority with STRA. Paediatric efficacy data of novel biologics and biomarkers that identify the optimal add-on for each child are lacking. If we are to progress toward individualized therapy for STRA, pragmatic clinical trials of biologics in accurately phenotyped children are needed.
Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Child; Disease Progression; Humans; Medication Adherence; Omalizumab; Phenotype; Precision Medicine; Severity of Illness Index
PubMed: 30720474
DOI: 10.1097/ACI.0000000000000521 -
Current Oncology Reports Jul 2021Until recently, improvement in terms of survival for patients with acute myeloid leukemia (AML) was achieved mostly in younger patients with dose intensification of... (Review)
Review
PURPOSE OF REVIEW
Until recently, improvement in terms of survival for patients with acute myeloid leukemia (AML) was achieved mostly in younger patients with dose intensification of conventional chemotherapy and a broadening use of allogeneic hematopoietic cell transplantation (allo-HCT) whereas the results remained dismal and very stable in patients older than 60 years. The current review highlights the recent developments in standard intensive post-remission chemotherapy, evidence for the use of recently approved agents, and discusses the relevance of measurable residual disease (MRD) measurement in treatment adaptation.
RECENT FINDINGS
Current approvals of midostaurin, venetoclax, gemtuzumab ozogamicin, VYXEOS, ivosidenib, enasidenib, glasdegib, and CC-486 have changed the structure, aim, and schedule of consolidation therapy, and new, well-tolerated agents are being evaluated as maintenance therapies. Furthermore, MRD assessment has been implemented to guide the duration and type of consolidation and maintenance therapy as well as indicate the optimal timing of allo-HCT. Novel therapies have changed the structure and perspective of post-remission therapy in AML for both young and elderly patients. In addition, MRD assessment could guide the type, duration, and intensity of consolidation and maintenance therapy.
Topics: Acute Disease; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid; Male; Middle Aged; Neoplasm, Residual; Remission Induction; Survival Analysis; Transplantation, Homologous
PubMed: 34272619
DOI: 10.1007/s11912-021-01092-0