Clinical advances in hematology & oncology : H&O
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Clin Adv Hematol Oncol · Oct 2016
ReviewCD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia.
Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. ⋯ We review the preclinical development of CAR T cells and their early clinical application for lymphoma. We also provide a comprehensive analysis of the use of CAR T cells in patients with B-ALL. In addition, we discuss the unique toxicities associated with this therapy and the management schemes that have been developed.
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Clin Adv Hematol Oncol · Sep 2016
ReviewThe role of high-dose melphalan and autologous stem cell transplant in the rapidly evolving era of modern multiple myeloma therapy.
The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma. ⋯ Moreover, unprecedented survival data from ongoing phase 3 studies of patients treated with modern myeloma therapy followed by HDM/ASCT in first-line or second-line therapy reaffirm single and tandem HDM/ASCT as important standards of care for eligible patients. Herein, we review the evolving role of HDM/ASCT for the treatment of patients with newly diagnosed or relapsed multiple myeloma.
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Clin Adv Hematol Oncol · Oct 2019
ReviewDelaying the use of high-dose melphalan with stem cell rescue in multiple myeloma is ready for prime time.
The significant advances made in the treatment of multiple myeloma (MM) have allowed for a paradigm shift away from the early use of high-dose melphalan with autologous stem cell transplant (HDM-ASCT). In 2015 alone, the US Food and Drug Administration (FDA) approved 4 novel drugs for MM. Novel drugs and regimens have shown unprecedented efficacy, which has increased the tempo of new drug development. ⋯ This article discusses the historic context of HDM-ASCT, the modern role of HDM-ASCT given the availability of highly sensitive MRD testing, and the likely future of quadruplet treatment. In summary, patients who attain deep responses using IMiD- and PI-based regimens may not require early HDM-ASCT. A delayed approach to this treatment is acceptable, and might be preferred by patients.
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Clin Adv Hematol Oncol · Jul 2019
ReviewRisk factors for and clinical management of venous thromboembolism during pregnancy.
Venous thromboembolism (VTE), which comprises deep vein thrombosis and pulmonary embolism, is one of the leading causes of non-obstetric maternal death in the United States. Physiologic and anatomic changes associated with pregnancy set the stage for a hypercoagulable state. In addition, other risk factors-including those associated with certain fetal characteristics such as low birth weight or stillbirth-have been correlated with an increased risk for VTE. ⋯ The choice of anticoagulant therapy for either treatment or prophylaxis in most cases is heparin, most commonly low-molecular-weight heparin. This is owing to the fact that vitamin K antagonists and the direct oral anticoagulants are contraindicated in pregnancy because of potential teratogenicity. With careful management and vigilant monitoring, appropriate anticoagulation can be used safely and effectively to improve patient outcomes.