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Vaccine-associated respiratory pathology correlates with viral clearance and protective immunity after immunization with self-amplifying RNA expressing the spike (S) protein of SARS-CoV-2 in mouse models.

In this study, we evaluated the immunogenicity and protective immunity of in vitro transcribed Venezuelan equine encephalitis virus (VEEV TC-83 strain) self-amplifying RNA (saRNA) encoding the SARS-CoV-2 spike (S) protein in wild type (S-WT) and stabilized pre-fusion conformations (S-PP). Immunization with S-WT and S-PP saRNA induced specific neutralizing antibody responses in both K18-Tg hACE2 (K18) and BALB/c mice, as assessed using SARS-CoV-2 pseudotyped viruses. Protective immunity was assessed in challenge experiments. Two immunizations with S-WT and S-PP induced protective immunity, evid

Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice.

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was ab

Impact of hyperthermic regional perfusion therapy on cell metabolism of malignant melanoma monitored by 31P MR spectroscopy.

For the first time, the influence of hyperthermic regional perfusion therapy on tumor cell metabolism has been monitored by means of 31P MR spectroscopy. Shortly after treatment, a complete depletion of high energy phosphates, a significant increase of inorganic phosphate, phosphomono- and phosphodiester resonances and a decrease of pH have been observed. Healthy muscle tissue showed only minor effects caused by this aggressive therapy. The time course of the transient variation of phosphate metabolite concentrations is explained in the framework of a simple pathophysiological model. The resul

[Autologous bone marrow transplantation in osteosarcoma].

Four patients with osteosarcoma were treated with intensive chemotherapy and autologous bone marrow transplantation (ABMT). The patients received high-dose methotrexate (9-12 mg/m2) with citrovorum factor rescue, high-dose melphalan (60 mg/m2 X 3), actinomycin D (0.5 mg/m2 X 3), adriamycin (30 mg/m2 X 2) and high-dose cyclophosphamide (60 mg/kg X 2) during 4 weeks. Bone marrow was aspirated and cryopreserved before treatment and reinfused 48 hours after the completion of chemotherapy. Two of four patients had advanced osteosarcoma with multiple pulmonary metastasis, one of whom had responded w…

Regional isolation perfusion in the treatment of advanced malignant disease.

Regional isolation perfusion with an alkylating agent was carried out in a small community hospital, using readily available equipment, ten times in nine cases of advanced malignant disease. Visible regression of tumor, either grossly or histologically, occurred in seven patients and decided subjective improvement occurred in five patients. The long range effect of the procedure could not be determined in the present series, not enough time having elapsed. Side effects included jaundice in four patients, massive necrosis of the tumor in one patient, nausea and vomiting in three patients, posto

Непоследовательные определения недопустимости трансплантации в миеломе: систематический обзор.

Высокодозвуковой мелфалан, за которым следует аутологическая трансплантация стволовых клеток (ASCT), является стандартом ухода за имеющими на это право пациентами с недавно поставленным диагнозом множественной миеломы (NDMM). Значительная доля пациентов считается не имеющими права на АЗСТ по причине возраста, соприкасаемости, качества работы и/или слабости. Критерии, определяющие невозможность пересадки, по-прежнему являются непоследовательными и плохо характеризуются. Мы провели систематический обзор, в ходе которого оценивались циклы II, III и IV выборочных контролируемых испытаний (РЦТ) до

Совпадение в аннотации оригинала
High-dose melphalan followed by autologous stem cell transplantation (ASCT) is the standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM). A substantial proportion of patients are deemed ineligible for ASCT due to age, comorbidities, performance status and/or frailty. Criteria defining transplant ineligibility remain inconsistent…

Autologous stem cell transplantation for AL amyloidosis: a multicenter summary of outcomes 2010-2020.

The role of autologous stem cell transplantation (ASCT) is central in AL amyloidosis and continues to be defined in the era of newer therapies. To evaluate contemporary patient selection, practice patterns, and outcomes, we conducted a retrospective, multicenter study across nine tertiary referral centers, including 1047 patients with AL amyloidosis who underwent ASCT between 2010 and 2020. Most patients (67.9%) received full-dose melphalan conditioning, and 66.5% received pre-ASCT induction therapy, predominantly proteasome inhibitor-based regimens. Day-100 all-cause mortality was 3.0%, repre…

Intra-arterial chemotherapy for retinoblastoma: a structured narrative review.

Retinoblastoma (Rb) is the most common primary intraocular malignancy in children. Intra-arterial chemotherapy (IAC), often termed ophthalmi … d globe salvage while reducing systemic toxicity when compared with intravenous chemotherapy. While melphalan remains the backbone chemotherapeutic agent, escalation to topotecan and/or carboplatin should be guided by tumor burden, vitreous or subretinal seeding, prior treatment response, evidence strength and expected functional potential. Functional prese …

Successful Engraftment After Repeat Cord Blood Transplantation Using an Identical Conditioning Regimen for MPS II.

Graft failure remains a major complication in cord blood transplantation (CBT), particularly in patients with nonmalignant diseases, such as … reduced-intensity conditioning regimen consisting of total abdominal irradiation, fludarabine, and melphalan. He acquired methicillin-resistant Staphylococcus aureus-associated sepsis early in the posttransplant period and developed graft failure on day 28, presumably due to drug-induced myelosuppression rather than insufficient conditioning intensity. Six …

Cost-Effectiveness Analysis of Daratumumab Monotherapy and Subsequent Therapies in Heavily Treated Relapsed/Refractory Multiple Myeloma: A Feasible Methodology using a Korean Nationwide Population Cohort.

PURPOSE: High-cost novel therapies for multiple myeloma (MM) require evaluation of efficacy and cost-effectiveness. MATERIALS AND METHODS: … val (OS) (p < 0.001), while all-cause medical costs increased with each LoT (p < 0.001). Bortezomib-melphalan-prednisolone was the most common frontline regimen for transplant-ineligible patients (29.2%), while bortezomib-thalidomide-dexamethasone was most used for transplant-eligible patients (11.3%). Daratumumab monotherapy demonstrated superior second TT …

Income and education affect prognosis and treatment in symptomatic myeloma : A population-based study on 8672 multiple myeloma patients diagnosed 2008-2021 from the Swedish myeloma registry.

Despite advancements in multiple myeloma treatment, prognostic variability persists. We investigated the impact of income and education on t … mide (HR 1.5, 95% CI 1.3-1.6) and pomalidomide (HR 1.7, 95% CI 1.4-2.0), and less likely to receive melphalan tablets (HR 0.8, 95% CI 0.7-0.9). Low-income patients were less likely to undergo stem cell transplant (HR 0.8, 95% CI 0.7-0.9). Immigrant status or biological sex did not influence outcomes. Even in a tax-funded system, socioeconomic disparities im …

A phase 2 trial of VRD induction for transplant-eligible Japanese patients with newly diagnosed multiple myeloma.

This single-arm phase 2 trial investigated the efficacy and safety of bortezomib-lenalidomide-dexamethasone (VRD) induction for transplant-eligible Japanese patients with newly diagnosed multiple myeloma. Treatment consisted of four cycles of VRD (bortezomib 1.3 mg/m2, s.c., days 1, 4, 8, 11; lenalidomide 25 mg/body/day, days 1-14; dexamethasone 40 mg/day, p.o., days 1, 4, 8, 11), stem cell mobilization with low-dose cyclophosphamide (1 g/m2, day 1) and bortezomib (1.3 mg/m2, days 4, 7), and high-dose therapy with melphalan supported by autologous peripheral blood stem cell transplantation. Pr…

A Novel Supermicrosurgery Training Model: Exercise for Lymphovenular Anastomosis.

Proficiency in supermicrosurgery is essential for successful lymphovenular anastomosis (LVA) procedures. Existing training models often lack … ed postoperatively. The model enabled dynamic observation of anastomoses, with patency confirmed by melphalan staining and manual perfusion tests. Trainees completed at least 20 anastomoses per session, demonstrating proficiency in both anastomosis techniques. The thin-walled lymphatic vessels closely resembled those in clinical lymphedema cases, providing …

Bortezomib-based induction therapy followed by autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients: A single-center experience and review of Indian literature.

INTRODUCTION: High-dose chemotherapy with melphalan, followed by autologous hematopoietic stem cell transplantation (AHCT) remains the standard of care for consolidation therapy of fit patients with newly diagnosed multiple myeloma (NDMM), for more than 20 years now. MATERIAL AND METHODS: This is a retrospective study of NDMM patients who underwent AHCT at our center from 2011 to 2018. Data was undertaken using the hospital electronic medical records (EMR). RESULTS: Among transplant eligible patients (which were 764), 78 patients (10.2%) underwent AHCT. The predominant stage in the study coh…

Allogeneic stem cell transplantation for inherited metabolic disorders: 35 years' experience at a single institution.

Hematopoietic stem cell transplants for inherited metabolic disorders performed at Tokai University Hospital between June 5, 1986, and May 2 … intravenous busulfan-based regimens or 4 Gy of thoracoabdominal irradiation (TAI), fludarabine, and melphalan (Mel)/treosulfan were adopted. Between 2002 and 2010, adrenoleukodystrophy was treated with 12 Gy of TAI and Mel. HLA-identical sibling bone marrow was used in 43% of cases before 2007 and 15% from 2007 onward, while alternative donors were selected …

TI17, a novel compound, exerts anti-MM activity by impairing Trip13 function of DSBs repair and enhancing DNA damage.

BACKGROUND: Thyroid hormone receptor interacting protein 13 (Trip13) is an AAA-ATPase that regulates the assembly or disassembly protein com … lly impaired Trip13 function of DSBs repair and enhanced DNA damage responses in MM. Combining with melphalan or HDAC inhibitor panobinostat triggers synergistic anti-MM effect. CONCLUSIONS: Our study suggests that TI17 could be acted as a specific inhibitor of Trip13 and supports a preclinical proof of concept for therapeutic targeting of Trip13 in MM.

Risk factors, treatments and outcomes of patients with light chain amyloidosis who relapse after autologous stem cell transplantation.

Relapse after ASCT is an important factor affecting the long-term prognosis of patients with AL amyloidosis. However, the risk factors of relapse are unknown and there are limited studies on treatment outcomes of these patients. We retrospectively reviewed 170 patients with AL amyloidosis who underwent ASCT between 2010 and 2021. Seventy-six patients confirmed as relapse and the median time from ASCT to relapse was 39 months. On multivariate analysis of variables before and after ASCT, lambda restricted, dFLC >30 mg/L pre ASCT, reduced dose melphalan and dFLC >10 mg/L at 6 months after ASCT we…

Romidepsin-induced durable remission for relapsed nodal peripheral T-cell lymphoma with T follicular helper phenotype after allogeneic hematopoietic cell transplantation.

Patients with recurrent peripheral T-cell lymphoma (PTCL) after allogeneic hematopoietic cell transplantation (HCT) have dismal outcomes. No … heral blood stem cell transplantation was performed using conditioning with fludarabine 180 mg/sqm, melphalan 80 mg/sqm, and total body irradiation 2 Gy, and graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide. One month after HCT, disease progression was observed in the lung. Romidepsin was readministered every 2 weeks a …

Successful HLA-haploidentical stem cell transplantation with post-transplant cyclophosphamide in an older patient with chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus infection (CAEBV) is a subtype of EBV-associated T/NK cell lymphoproliferative disease and is only curable … l transplantation (haplo-SCT) with reduced-intensity conditioning (fludarabine 25 mg/m2 for 5 days, melphalan 50 mg/m2 for 2 days, and total body irradiation at 2 Gy) and post-transplant cyclophosphamide (PTCy) because she lacked an HLA-matched donor. Liver function was restored, and EBV DNA load in peripheral white blood cells became undetectable. The pati …