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Clinical and economic burden associated with graft-versus-host disease following allogeneic hematopoietic cell transplantation in France.

The real-world clinical and economic burden of graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation has not been comprehensively studied in France. Clinical outcomes, healthcare resource utilization and costs associated with acute GVHD (aGVHD), chronic GVHD (cGVHD), acute plus chronic GVHD (a+cGVHD) versus no GVHD were compared using French administrative claims data. After propensity score matching, 1934, 408, and 1268 matched pairs were retained for the aGVHD, cGVHD, and a+cGVHD cohorts, respectively. Compared with patients with no GVHD, odds of devel

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… 0.888 Ciclosporin 593 (30.7) 1499 (77.5) −1.065 350 (85.8) 333 (81.6) 0.113 494 (39.0) 2064 (77.4) −0.828 Mycophenolate mofetil 324 (16.8) 601 (31.1) −0.341 141 (34.6) 118 (28.9) 0.121 242 (19.1) 845 (31.7) −0.257 Tacrolimus 39 (2.0) 89 (4.6) −0.145 53 (13.0) 19 (4.7) 0.297 43 (3.4) 123 (4.6) −0.107 Sirolimus … 350 (85.8) | 333 (81.6) | 0.113 | 494 (39.0) | 2064 (77.4) | −0.828 Mycophenolate mofetil | 324 (16.8) | 601 (31.1) | −0.341 | 141 (34.6) | 118 (28.9) | 0.121 | 242 (19.1) | 845 (31.7) | −0.257 Tacrolimus | 39 (2.0) | 89 (4.6) | −0.145 | 53 (13.0) | 19 (4.7) | 0.297 | 43 (3.4) | 123 (4.6) | −0.107 Sirolimus …

Current cancer therapies and their influence on glucose control.

This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes. These groups of medications were selected due to their significant association with new onset hyperglycemia, or of potentially severe clinical consequences when present. These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments, and the antimetabolite class of 5-fluorouracil-related drugs. Both of these classes have been in use in cancer therapy since the 1950s. Also considered are the phosphatidyl inositol-3-kinase (PI3K)/AKT

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… There are presently three mTOR inhibitors approved by the United States Food and Drug Administration (FDA) that are derivatives of rapamycin; sirolimus, temsirolimus, and everolimus. … The three mTOR inhibitors approved by the FDA are derivatives of rapamycin; sirolimus, temsirolimus, and everolimus, and are primarily mTORC1 inhibitors, although dual mTORC1/C2 inhibitors are in development[ 57 ]. …

The 45th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Session.

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The safety and efficacy of a novel hypo-fractionated total marrow and lymphoid irradiation before allogeneic stem cell transplantation for lymphoma and acute leukemia.

PURPOSE: Total body irradiation (TBI) has been widely utilized as part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT), but is associated with significant toxicities. Targeted TBI using helical Tomotherapy allows precise and homogeneous tumor coverage and excellent sparing of organs at risk. The purpose of this study was to evaluate the clinical outcomes of a novel hypo-fractionation strategy for patients receiving total marrow and involved lymphoid irradiation (TMLI) as part of the conditioning regimen before HSCT. METHODS AND MATERIALS: 61 patients (7 acute my

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… GVHD prophylaxis consisting of tacrolimus and sirolimus was also started on day −1. On Day 0, collected peripheral blood stem cells from HLA-matched related (45 patients) or matched unrelated donors (16 patients) was infused. …

The effect of oral chronic graft-versus-host disease on bodyweight: A cohort study.

AimThis retrospective cohort study aimed to evaluate the association between body weight and oral cGVHD (chronic graft versus host disease).MethodsPatients with oral cGVHD were compared with an age and gender-matched non-GVHD cohort in terms of demographic information, body mass index (BMI), date of transplant, length of hospitalization, and oral complications. Weight was stratified in pre-and post-transplant weight, mean weight after acquiring cGVHD for the first year, and post-oral cGVHD BMI. Each patient was matched and compared with two controls at a 1:2 ratio. Firth's penalized likelihood

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… Mammalian target of rapamycin inhibitor–associated stomatitis in hematopoietic stem cell transplantation patients receiving sirolimus prophylaxis for graft-versus-host disease. Biology of Blood and Marrow Transplantation. 2015;21(3):503–8. doi: 10.1016/j.bbmt.2014.11.680 23. …

High prevalence of potential drug interactions affecting mycophenolic acid pharmacokinetics in nonmyeloablative hematopoietic stem cell transplant recipients.

ObjectiveMycophenolic acid (MPA) exposure is associated with clinical outcomes in hematopoietic cell transplant (HCT) recipients. Various drug interaction studies, predominantly in healthy volunteers or solid organ transplant recipients, have identified medications which impact MPA pharmacokinetics. Recipients of nonmyeloablative HCT, however, have an increased burden of comorbidities, potentially increasing the number of concomitant medications and potential drug interactions (PDI) affecting MPA exposure. Thus, we sought to be the first to characterize these PDI in nonmyeloablative HCT recipi

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… leukemia | 3 (4%) Other | 6 (7%) HCT comborbidity index b 0 | 8 (10%) 1 – 2 | 13 (15%) 3 – 4 | 31 (37%) ≥ 5 | 30 (36%) End organ dysfunction c Renal dysfunction d | 11 (13%) Liver dysfunction e | 12 (14%) Postgrafting immunosuppression concomitant with MMF Cyclosporine | 58 (69%) Tacrolimus | 26 (31%) Sirolimus …

Clinical and Laboratory Features of Hemophagocytic Lymphohistiocytosis in People With Disseminated Histoplasmosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome involving pathologic excitation of the immune system. Disseminated histoplasmosis (DH) is a known trigger of HLH. However, the prevalence of HLH in DH is unknown. Limited data exist on risk factors and outcomes. The goals of this study are to determine the prevalence of HLH among participants with DH at a single center, identify risk factors for HLH in this population, and describe the treatment and outcomes of people with DH and HLH. METHODS: We retrospectively identified cases of DH at our institution from 2

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… Abbreviations: P , participant number; IS, immunosuppression; HC, hydrocortisone; IVIG, intravenous immune globulin; dex, dexamethasone; pred, prednisone; TAC, tacrolimus; MMF, mycophenolate mofetil; SRL, sirolimus; RA, rheumatoid arthritis; DLBCL, diffuse large B-cell lymphoma; R-CHOP, cyclophosphamide …

Extracorporeal Photopheresis in Pediatric and Adult Patients with Graft-Versus-Host Disease.

Background/Objectives: Graft-versus-host disease (GVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) resulting from histocompatibility differences between donor and host cells leading to inflammation, tissue damage, and compromised patient outcome. Extracorporeal photopheresis (ECP) is considered as a second-line treatment administered to patients with GVHD who do not respond to corticosteroid treatment or who experience a relapse after an initial response and are therefore classified as steroid refractory (SR). The aim of this study is to evaluate

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… These may include immunosuppressants, such as mycophenolate mofetil and sirolimus; extracorporeal photopheresis (ECP); anti-TNF-α and anti-IL-2R antibodies; selective Janus kinase (JAK) 1 and 2 (ruxolitinib) inhibitors; and cell therapies, including mesenchymal stem cells [ 1 , 2 ]. …

Combination of Novel Therapies and New Attempts in Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies, and it is rapidly falling without any effective therapeutic options. Although radical surgery, radiotherapy, and chemotherapy are performed on patients, the curative effect is suboptimal, and the survival rate is still poor. The discovery of altered gene pathways involved in this aggressive disease has advanced, but molecular targeted drugs targeting these pathways are still in clinical trials. To date, there is no effective way to treat this disease, so it is particularly urgent to find new treatments. At present, m

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… There was no ORR in the evaluated patients, and one patient had SD = 12 months. 32 mTOR inhibitor Everolimus is a sirolimus-derived mTOR inhibitor. Constitutive activation of the phosphatidylinositol-3-kinase (PI3 K)/AKT/mTOR pathway has been reported in the pathogenesis of thyroid cancer. …

Noninfectious pulmonary complications of haematopoietic stem cell transplantation.

Haematopoietic stem cell transplantation (HSCT) is an established treatment for a variety of malignant and nonmalignant conditions. Pulmonary complications, both infectious and noninfectious, are a major cause of morbidity and mortality in patients who undergo HSCT. Recent advances in prophylaxis and treatment of infectious complications has increased the significance of noninfectious pulmonary conditions. Acute lung injury associated with idiopathic pneumonia syndrome remains a major acute complication with high morbidity and mortality. On the other hand, bronchiolitis obliterans syndrome is

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… Fludarabine- and sirolimus-induced pulmonary toxicity are under recognised but respond to treatment with corticosteroids [ 89 , 90 ]. Anti-thymocyte globulin has been reported to cause drug-induced noncardiogenic pulmonary oedema and acute respiratory distress syndrome [ 91 ]. … Sirolimus-associated pulmonary toxicity. Transplantation 2004; 77: 1215–1220. doi: 10.1097/01.TP.0000118413.92211.B6 91. Goligher EC, Cserti-Gazdewich C, Balter M, et al. Acute lung injury during antithymocyte globulin therapy for aplastic anemia. …

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

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… 12, 2006 | Completed NCT03190174 | Nivolumab (Opdivo®) plus ABI‐009 (Nab‐rapamycin) for advanced sarcoma and certain cancers | Colorectal cancer and other cancers | Drug: Nab‐Rapamycin Biological: Nivolumab | Phase 1 Phase 2 | June 16, 2017 | Recruiting NCT01522820 | Vaccine therapy with or without sirolimus … with grapefruit juice for advanced malignancies | Tumors Neoplasm metastasis | Drug: rapamycin (sirolimus) Other: grapefruit juice | Phase 1 | September 12, 2006 | Completed NCT02465060 | Targeted therapy directed by genetic testing in treating patients with advanced refractory solid tumors, lymphomas …

Tuberous sclerosis-2 (TSC2) regulates the stability of death-associated protein kinase-1 (DAPK) through a lysosome-dependent degradation pathway.

We previously identified a novel interaction between tuberous sclerosis-2 (TSC2) and death-associated protein kinase-1 (DAPK), the consequence being that DAPK catalyses the inactivating phosphorylation of TSC2 to stimulate mammalian target of rapamycin complex 1 (mTORC1) activity. We now report that TSC2 binding to DAPK promotes the degradation of DAPK. We show that DAPK protein levels, but not gene expression, inversely correlate with TSC2 expression. Furthermore, altering mTORC1 activity does not affect DAPK levels, excluding indirect effects of TSC2 on DAPK protein levels through changes in

Global perspectives on lupus nephritis: a review of clinical trials and therapeutic innovations.

BACKGROUND AND OBJECTIVES: Lupus nephritis (LN) remains a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE). Although recent years have witnessed the approval of several targeted therapies, achieving long-term, drug-free remission remains challenging. This commentary evaluates the global landscape of interventional LN clinical trials from 2001 to 2026 to identify emerging trends and strategic gaps in drug development. METHODS: We analyzed 200 interventional pharmacological trials retrieved from three major global registries: ClinicalTrials.gov, Chinadrugtrials.org

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… 6R monoclonal antibody) | United States | NCT00001789 (Completed) | Phase II | 2002 | BG9588 (anti-CD40L Antibody) | United States | III, IV NCT00976300 (Completed) | Phase II | 2002 | Cyclosporine A, Intravenous Cyclophosphamide (CTX) | Czechia | III, IV NCT00050713 (Completed) | Phase II | 2002 | Sirolimus … Sirolimus | mTOR inhibitor (Inhibits T-cell activation and proliferation) | Off-Label / Second-Line Option. FDA approved for renal transplantation. Used in LN for specific refractory cases or to minimize CNI/steroid toxicity (mTOR pathway blockade). …

Molecular targeted therapy for anticancer treatment.

Since the initial clinical approval in the late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served as a fundamental backbone in precision medicine for cancer treatment. These approaches are now used clinically as first-line therapy for various types of human cancers. Compared to conventional chemotherapy, targeted therapeutic agents have efficient anticancer effects with fewer side effects. However, the emergence of drug resistanc

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… DFG-Asp out) | dasatinib, imatinib, lapatinib, lenvatinib, nilotinib, regorafenib, sorafenib, sunitinib, vemurafenib Type III Type IV | Allosteric inhibitors binding to a site in the kinase domain either next to the ATP-binding pocket or remote from the ATP-binding pocket | trametinib, everolimus, sirolimus … Examples of clinically utilized PI3K (e.g., idelalisib, duvelisib, copanlisib and alpelisib) and mTOR inhibitors (e.g., sirolimus, temsirolimus, and everolimus) are listed in Table 5 . …

A Phase Ib Investigator-Initiated Trial of Filgotinib in Patients With Idiopathic Multicentric Castleman Disease.

Background Idiopathic multicentric Castleman disease (iMCD) is a chronic systemic inflammatory disease characterized by the production of interleukin (IL)-6. The contribution of Janus kinase, downstream of IL-6 signaling, to the pathophysiology of iMCD has been suggested by several studies. Patients and methods This phase Ib single-arm trial evaluated the safety profile and efficacy of filgotinib, a JAK1 preferential inhibitor, in patients with iMCD. We recruited patients with disease activity evaluated based on their values of C-reactive protein (CRP), hemoglobin, albumin, and Eastern Coopera

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… Patients who had received an immunosuppressant (tacrolimus, cyclosporine, azathioprine, mizoribine, or sirolimus), JAK inhibitor (tofacitinib, baricitinib, peficitinib, upadacitinib, ruxolitinib, abrocitinib, ritrecitinib, or delgocitinib), or carotegrast within 14 days before enrollment (topical use …

Alemtuzumab и тромбоцитопентия: анализ международной базы данных наблюдения и систематический обзор литературы.

ЦЕЛИ: Trombotic trombytopenic purpura (TTP) — тромботическая микроангиопатия, связанная с острым дефицитом в ADAMTS13. Дефицит ADAMTS13 может быть вторичным по отношению к отсутствующему или дисфункциональному производству белка в результате мутаций в гене ADAMTS13 (наследственный TTP) или в виде удаления и/или ингибирования с помощью самозащиты (иммунизированный TTP). Этот аутоиммунитет может, хотя и редко, быть вторичным по отношению к некоторым лекарствам (например, к тиклопидину). Согласно последним сообщениям, алемтузумаб (ЛЕТРАДА) является моноколональным антителом, который избирательно

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… Ten reports documented concomitant or suspected use of CIs or mammalian target of rapamycin (mTOR) inhibitors, with four reports indicating 2 different CIs/mTOR inhibitors (tacrolimus, n = 7; cyclosporine, n = 6; sirolimus, n = 1; everolimus, n = 1). …

Extracorporeal photopheresis vs standard therapies for steroid-refractory chronic graft-vs-host disease: Pharmacoeconomic assessment of hospital resource use in Spain.

BackgroundThis study assessed pharmacoeconomic costs associated with extracorporeal photopheresis (ECP) compared with other available second-line therapies for chronic graft-vs-host disease (cGvHD) in a tertiary Spanish institution.MethodsPatients (≥18 years) diagnosed with steroid-refractory cGvHD were eligible. Data were collected retrospectively from index date until 1 year or relapse. Patients were distributed in two cohorts (ECP vs non-ECP), matched by age (≤ or > 40), hematopoietic stem cell transplant (HLA-identical sibling donor or other) and number of previous immunosuppressive lines

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… (25) | 2 (10) | Peripheral blood | 14 (70) | 18 (90) | Type of ECP, n (%) | ‐ Integrated | 7 (35) | ‐ | Two‐step procedure | 13 (65) | ‐ | Concomitant treatments for cGvHD, n (%) | .23 Steroids dose increased | 4 (20) | 5 (25) | Steroids + calcineurin inhibitors | 6 (30) | 2 (10) | Steroids + sirolimus …

Burden of Seasonal Human Coronavirus Infections in Hematopoietic Cell Transplant Recipients.

BackgroundCommunity respiratory viruses, such as seasonal human coronavirus (HCoV), commonly infect hematopoietic cell transplant (HCT) recipients. Recognizing the risk factors and outcomes of HCoV infections in HCT recipients is essential for the future development of potentially lifesaving therapeutics.MethodsWe performed a retrospective review of all HCoV-infected HCT recipients from September 1, 2015 to August 31, 2017, at our institution. Patients were classified with upper respiratory tract infection (URI) or lower respiratory infection (LRI) based on predefined definitions for respirato

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… ; ANC, absolute neutrophil count; GVHD, graft versus host disease; HCT, hematopoietic cell transplantation; ISI, immunodeficiency scoring index; LRI, lower respiratory tract infection; URI, upper respiratory tract infection. a Mycophenolate mofetil, alemtuzumab, anti‐thymocyte globulins, rituximab, sirolimus …

Knowledge of Dental Students and Practitioners About Medication-Related Osteonecrosis of the Jaw in the Central Region of Saudi Arabia.

BACKGROUND: Bisphosphonates (BPs) are often used in treating benign and malignant disorders. Medication-related osteonecrosis of the jaw (MRONJ) is a significant problem that arises from the long-term use of BPs. OBJECTIVE: In this study, we assessed the knowledge of students and dentists about MRONJ in the central region of Saudi Arabia. METHODS: A cross-sectional study was conducted to collect information from dental students and practitioners from the central region of Saudi Arabia. A valid, reliable, and structured questionnaire was used to gather data using a non-probability convenient

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… Bevacizumab (Avastin, Roche, Basel, Switzerland) | 7% (8) | 10.3% (14) | 0.288 Denosumab (Xgeva and Prolia, Amgen, Thousand Oaks, California, United States) | 13.2% (15) | 20.6% (28) Sirolimus (Rapamune, Pfizer, New York, New York, United States) | 2.6% (3) | 4.4% (6) Sorafenib (Nexavar, Bayer, Berlin …

Blast Transformation of Chronic Myeloid Leukemia Driven by Acquisition of t(8;21)(q22;q22)/RUNX1::RUNX1T1: Selecting Optimal Treatment Based on Clinical and Molecular Findings.

The advent of tyrosine kinase inhibitors (TKIs) has changed the natural history of chronic myeloid leukemia (CML), and the transformation from the chronic phase to the blast phase (BP) is currently an uncommon situation. However, it is one of the major remaining challenges in the management of this disease, as it is associated with dismal outcomes. We report the case of a 63-year-old woman with a history of CML with poor response to imatinib who progressed to myeloid BP-CML, driven by the acquisition of t(8;21)(q22;q22)/RUNX1::RUNX1T1. The patient received intensive chemotherapy and dasatinib,

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… Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus plus sirolimus plus mycophenolate. As early complications after allogeneic transplantation, the patient developed digestive mucositis grade 3 and an episode of febrile neutropenia, which were successfully resolved [ 17 ]. …