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Toxicity Profile of Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapies in Multiple Myeloma: Pathogenesis, Prevention and Management.

Multiple myeloma is the second-most common hematologic malignancy in adults worldwide. Despite ongoing advancement in therapeutic modalities, it remains an incurable disease with a 5-year survival rate of approximately 50%. The recent development and introduction of anti-BCMA immunotherapies into clinical practice, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies, has radically shifted the treatment paradigm. However, despite the promising potential of these therapies for broader application, frequent and significant adverse effects have been reported, bot

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… G-CSF as given to 88% of patients, red blood cell transfusions to 63%, platelet transfusions to 42%, thrombopoietin receptor (TPO) agonist to 21%, IVIG to 13%, and CD34+ stem cell boost to 8%. On day +100, 19% and 13% of patients were on a TPO agonist and G-CSF, respectively. …

Ibrutinib in Combination with Lenalidomide Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma (AFT-15).

BackgroundStudies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival.MethodA 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3,

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… Dose-limiting toxicities (DLTs) included the following events occurring during the first cycle of treatment: grade 4 thrombocytopenia; grade 4 neutropenia lasting more than 5 days or febrile neutropenia; grade 3 thrombocytopenia with bleeding or platelet transfusion; grade 3–4 hyperglycemia or a thrombotic …

Pharmacological treatments of COVID-19.

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and

First-in-human Study of AZD5153, A Small-molecule Inhibitor of Bromodomain Protein 4, in Patients with Relapsed/Refractory Malignant Solid Tumors and Lymphoma.

AZD5153, a reversible, bivalent inhibitor of the bromodomain and extraterminal family protein BRD4, has preclinical activity in multiple tumors. This first-in-human, phase I study investigated AZD5153 alone or with olaparib in patients with relapsed/refractory solid tumors or lymphoma. Adults with relapsed tumors intolerant of, or refractory to, prior therapies received escalating doses of oral AZD5153 once daily or twice daily continuously (21-day cycles), or AZD5153 once daily/twice daily continuously or intermittently plus olaparib 300 mg twice daily, until disease progression or unacceptab

Clinical development of gene therapy: results and lessons from recent successes.

Therapeutic gene transfer holds the promise of providing lasting therapies and even cures for diseases that were previously untreatable or for which only temporary or suboptimal treatments were available. For some time, clinical gene therapy was characterized by some impressive but rare examples of successes and also several setbacks. However, effective and long-lasting treatments are now being reported from gene therapy trials at an increasing pace. Positive outcomes have been documented for a wide range of genetic diseases (including hematological, immunological, ocular, and neurodegenerativ

Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016.

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial

Advances in CAR-T-cell therapy in T-cell malignancies.

Significant advances have been made in chimeric antigen receptor T (CAR-T)-cell therapy for the treatment of recurrent or refractory B-cell hematologic malignancies. However, CAR-T-cell therapy has not yet achieved comparable success in the management of aggressive T-cell malignancies. This article reviews the challenges of CAR-T-cell therapy in treating T-cell malignancies and summarizes the progress of preclinical and clinical studies in this area. We present an analysis of clinical trials of CAR-T-cell therapies for the treatment of T-cell malignancies grouped by target antigen classificati

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… Treatment typically involves closely monitoring the patient and providing supportive care, including prophylactic antibiotics, blood transfusions, and platelet transfusions [ 111 , 112 ]. … Managing these complications typically involves a combination of prophylactic antibiotics, corticosteroids to mitigate inflammation, and supportive therapies such as blood or platelet transfusions for bleeding tendencies. …

Mechanistic Insights in Hemophagocytic Lymphohistiocytosis: Subsequent Acute Hepatic Failure in a Multiple Myeloma Patient Following Therapy with Ixazomib-Lenalidomide-Dexamethasone.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, elusive, and life-threatening condition that is characterized by the pathologic and uncontrolled secondary activation of the cytotoxic T-cells, natural killer cells (NK-cells), and macrophages of the innate immune system. This condition can develop in sporadic or familial contexts associated with hematological malignancies, as a paraneoplastic syndrome, or linked to an infection related to immune system deficiency. This leads to the systemic inflammation responsible for the overall clinical manifestations. Diagnosis should be thorough, and tr

Maintenance therapy in acute myeloid leukemia: advances and controversies.

The last decade has seen steadfast progress in drug development in acute myeloid leukemia (AML) which has moved progressively towards genomic-based therapy. With these advances, outcomes in AML have improved but remains far from satisfactory. One approach towards preventing relapse in AML is to use maintenance therapy in patients, after attaining remission. Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective post-remission therapy that has been proven to reduce the risk of relapse. However, in patients who are ineligible for HSCT or have a high risk of relapse, other effe

Минимальная информация для исследований внеклеточной везиклетки (MISEV2023): от базовых до передовых подходов.

Внеклеточные везиклолы (ЭМ) с помощью своего сложного груза могут отражать состояние клетки их происхождения и изменять функции и фенотипы других ячеек. Эти особенности свидетельствуют о значительном биомаркировании и терапевтическом потенциале и вызывают широкий интерес, о чем свидетельствует постоянное увеличение числа научных публикаций об ЭМ за год. Значительные успехи были достигнуты в области ЭВМ, а также в понимании и применении биологии ЭМ. Вместе с тем сохраняются препятствия на пути реализации потенциала ЭМ в различных областях - от базовой биологии до клинического применения - в свя

Осуществимость консолидации после вводного курса с клеточной терапией BCMA CAR-T в недавно диагностированном миеломе, не поступающей в ASCT: предварительная серия дел.

Антигенная химериковая антигенная терапия (CAR) T клеточная терапия B-клеток (BCMA) продемонстрировала многообещающую эффективность при повторном/изобилии множественной миеломы (MM). Однако доказательства, подтверждающие его использование в более ранних лечебных условиях, по-прежнему ограничены. В настоящем исследовании представлена предварительная серия дел, в которой оценивается практическая возможность применения клеточной терапии BCMA CAR-T в качестве клеточной терапии в период после ввода у недавно диагностированных пациентов с несколькими миеломой (NDMM), которые не перешли к автоматичес

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… No patient required red blood cell transfusions, while only patient 3 required platelet transfusion support. Infectious complications occurred in patients 3 and 4 and improved with appropriate treatment. …

Molecular Guided Therapy Provides Sustained Clinical Response in Refractory Choroid Plexus Carcinoma.

Choroid plexus carcinomas (CPCs) are rare, aggressive pediatric brain tumors with no established curative therapy for relapsed disease, and poor survival rates. TP53 Mutation or dysfunction correlates with poor or no survival outcome in CPCs. Here, we report the case of a 4 month-old female who presented with disseminated CPC. After initial response to tumor resection and adjuvant-chemotherapy, the tumor recurred and metastasized with no response to aggressive relapse therapy suggesting genetic predisposition. This patient was then enrolled to a Molecular Guided Therapy Clinical Trial. Genomic

Доклад по делу: Выяснение роли генетических аномалий в миэломатном плевральном эффюляции: случай с несколькими миеломами типа IgG Lambda.

A 73-year-old Мужчина с многократной миеломой, с постепенно ухудшающейся болью в левом плече, которая не реагировала на консервативное управление. После проведения всеобъемлющих диагностических процедур, включая съемку и генетическое тестирование, у него был диагностирован множественный миэлома типа IgG Lambda, осложненный развитием миэломатного плеврального эффюля (MPE). Лечение пациента состояло из сочетания химиотерапии PDD, включая Бортезомиб, Доксорубицин и Дексаметазон, наряду с адъюнктивными терапиями, направленными на контроль плевральной эфлуции. Оценка после обработки выявила разреше

Clinically significant bleeding in incurable cancer patients: effectiveness of hemostatic radiotherapy.

BackgroundThis study was performed to evaluate the outcome after hemostatic radiotherapy (RT) of significant bleeding in incurable cancer patients.MethodsPatients treated by hemostatic RT between November 2006 and February 2010 were retrospectively analyzed. Bleeding was assessed according to the World Health Organization (WHO) scale (grade 0 = no bleeding, 1 = petechial bleeding, 2 = clinically significant bleeding, 3 = bleeding requiring transfusion, 4 = bleeding associated with fatality). The primary endpoint was bleeding at the end of RT. Key secondary endpoints included overall survival (

Allogeneic stem cell transplantation for patients with advanced hematological malignancies: comparison of fludarabine-based reduced intensity conditioning versus myeloablative conditioning.

We compared the outcomes of allogeneic hematopoietic stem cell transplantation using reduced intensity and myeloablative conditioning for the treatment of patients with advanced hematological malignancies. A total of 75 adult patients received transplants from human leukocyte antigen-matched donors, coupled with either reduced intensity (n=40; fludarabine/melphalan, 28; fludarabine/cyclophosphamide, 12) or myeloablative conditioning (n=35, busufan/cyclophosphamide). The patients receiving reduced intensity conditioning were elderly, or exhibited contraindications for myeloablative conditioning

Actinium-225-PSMA-617 treatment in a patient with advanced prostate cancer causes secondary myelofibrosis: a case report and literature review.

Advanced prostate cancer (PCa) is still an incurable disease. Still, the field of PSMA-targeted radioligand therapy is developing rapidly and is playing an increasingly important role in the treatment of advanced Pca in the future. As an α -particle emitter, Ac-225 shows a potent killing ability for tumor cells due to its short range and high energy deposition in the tumor micrometastasis focus. However, the secondary myelofibrosis (SMF) associated with Ac-225-PSMA-617 treatment is a significant concern. We present a case of metastatic castration-resistant prostate cancer (mCRPC) who developed

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

Emergency Combination of Four Drugs for Bloodstream Infection Caused by Carbapenem-Resistant Enterobacteriaceae in Severe Agranulocytosis Patients with Hematologic Malignancies after Hematopoietic Stem Cell Transplantation.

Bloodstream infection (BSI) caused by multidrug-resistant (MDR) bacteria or extensively drug-resistant (XDR) bacteria is a global threat. However, an effective treatment regimen is still controversial and inadequate due to the rapid deterioration caused by the bacteria. In immunocompromised and neutropenic patients, MDR-BSI is an emergency, which causes treatment-related mortality. In this study, four agranulocytosis patients with hematologic malignancies after HSCT receiving treatment for carbapenem-resistant Enterobacteriaceae- (CRE-) BSI were included. Conventional treatment using two to th

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… Supportive Care Packed red blood cells and platelet transfusions were administered when patient hemoglobin level and platelet counts dropped below 60 g/L and 20 × 10 9 cells/L, respectively. …

Engraftment Syndrome: A Retrospective Analysis of the Experience at a Tertiary Care Institute.

Engraftment syndrome (ES) is a clinical syndrome that occurs in the early neutrophil recovery phase following hematopoietic stem cell transplant (HSCT). Although also described for allogenic HSCT, it is basically diagnosed in the context of autologous HSCT. We retrospectively reviewed 171 consecutive HSCTs performed between January 2013 and January 2015 in our Bone Marrow Transplant (BMT) unit and analyzed all cases of noninfectious fever and strong clinical features suggestive of ES in the peri-engraftment period for up to 7 days. We observed the incidence of ES to be 12.3% (16/130) in the au

Monoclonal Gammopathy of Undetermined Significance Diagnosed by Persistent Anemia Following Living Kidney Transplantation: A Case Report.

The prevalence of monoclonal gammopathy of undetermined significance increases with age, and there may be undiagnosed patients among kidney transplant recipients. A 69-year-old woman underwent ABO-incompatible living-donor kidney transplantation. Her renal function improved immediately postoperatively. Her hemoglobin level gradually increased to 10.5 g/dL at 3 months postoperatively but gradually decreased to 7.3 g/dL at 9 months postoperatively. We administered an erythropoiesis-stimulating agent and consulted the Department of Hematology. Bone marrow aspiration revealed that the pathological