Thrombopoietin receptor agonists for chemotherapy-induced thrombocytopenia: a new solution for an old problem

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Shifting landscape of hemophilia therapy: Implications for current clinical laboratory coagulation assays

Clinical coagulation assays are an integral part of diagnosing and managing patients with hemophilia; however, in this new era of bioengineered factor products and nonfactor therapeutics, problems have arisen with use of traditional coagulation tests for the quantification of several of these new products. Discussion over the use of one‐stage clotting assays versus chromogenic substrate assays for clinical decision making and potency labeling has been ongoing for many years. Emerging factor concentrates have heightened concern over assay selection and availability. Emicizumab interferes with all aPTT based assays, rendering them unreliable and potentially falsely reassuring to the unaware provider. This review explores considerations for coagulation assays in the clinical setting and highlights how awareness of institutional coagulation assays and potential limitations have never been more critical for providers caring for patients with bleeding disorders.     

Ofatumumab for acute treatment and prophylaxis of a patient with multiple relapses of acquired thrombotic thrombocytopenic purpura

Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder resulting in potentially life-threating systemic thrombotic microangiopathy due to production of antibodies directed against the von Willebrand factor-cleaving protease ADAMTS13. Typically managed with plasma exchange, glucocorticoids, and the first-generation anti-CD20 monoclonal antibody rituximab, patients with multiple relapses or refractory disease present unique management challenges. We describe a case of a young woman with multiple relapses of TTP despite standard therapy who was treated with ofatumumab, a second-generation anti-CD20 monoclonal antibody, after developing a severe hypersensitivity reaction to rituximab precluding its use. Ofatumumab was effective for the treatment of an acute relapse of TTP in combination with plasmapheresis and as a single-agent for prophylaxis. The patient has had no evidence of relapse 2 years after completion of acute treatment and 1 year after completing prophylactic therapy. Hypersensitivity to ofatumumab did not develop.     

Generation of autologous cytotoxic and helper T-cell responses against the B-cell leukemia-associated antigen HB-1: relevance for precursor B-ALL-specific immunotherapy

Tumor relapses in patients with precursor B-cell acute lymphoblastic leukemia (BALL) occur frequently after primary treatment. Therefore, development of additional treatment modalities to eliminate residual tumor cells is needed. Active immunotherapy using dendritic cells (DCs) loaded with tumor-associated antigens is a promising approach to induce specific T-cell immunity in patients with cancer. In previous studies, we described HB-1 as a B-cell lineage-specific antigen that is recognized by donor-derived cytotoxic T lymphocytes (CTLs) on allogeneic B-ALL tumor cells. Here, we investigated the potential use of the HB-1 antigen as an autologous T-cell vaccine target. To determine whether HB-1-specific CTL precursors are present within the T-cell repertoire, we induced expansion of CD8+ T cells using mature monocyte-derived DCs pulsed with the previously identified HB-1.B44 antigenic peptide. In 6 of 8 donors, CD8+ CTL lines have been generated that exert cytotoxicity against target cells exogenously pulsed with peptide or endogenously expressing the HB-1 antigen. From one of these HB-1-specific T-cell lines, we isolated a CD8+ CTL that produces interferon-gamma on stimulation with B-ALL tumor cells. Interestingly, the HB-1 antigen also induced CD4+ T-helper responses on activation with protein-loaded mature monocyte-derived DCs. We identified 2 novel epitopes recognized in the context of HLA-DR4 and HLA-DR11 with the use of HB-1-specific CD4+ T-cell clones generated from different donors. These present data, that HB-1 induces both helper and cytotoxic T-cell responses, indicate that the HB-1 antigen is a candidate target to induce T-cell-mediated antitumor immunity in patients.