ABSTRACT
Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency characterized by microangiopathic hemolytic anemia and thrombocytopenia. Plasma exchange is the standard treatment. Treating TTP without plasma exchange is a challenge. Due to religious beliefs, Jehovah's Witnesses do not accept transfusions of blood products. We report a case of successful treatment of TTP in a Jehovah's Witness using plasma exchange with albumin replacement.
Subject(s)
Jehovah's Witnesses , Plasma Exchange/methods , Purpura, Thrombotic Thrombocytopenic/therapy , ADAM Proteins/antagonists & inhibitors , ADAM Proteins/blood , ADAMTS13 Protein , Adult , Albumins/administration & dosage , Dexamethasone/administration & dosage , Disease Management , Erythropoietin/administration & dosage , Female , Humans , Immunoglobulins, Intravenous/administration & dosage , Platelet Count , Purpura, Thrombotic Thrombocytopenic/blood , Recombinant Proteins/administration & dosage , Rituximab/administration & dosage , Vincristine/administration & dosageABSTRACT
Monoclonal antibodies (mAbs) are increasingly used in treatment protocols for chronic lymphocytic leukemia (CLL). Here we determined (i) the extent of antibody-dependent cellular cytotoxicity (ADCC) of four different mAbs against primary CLL cells, (ii) whether ADCC correlates with antigen density on CLL cells, and (iii) whether allogeneic natural killer (NK) cells display superior ADCC than autologous. Effector cells for ADCC were (i) NK-92 cells not expressing FcR, (ii) NK-92 cells transfected with a high-affinity Fc receptor, (iii) autologous NK cells from patients with CLL, (iv) allogeneic NK cells. Results suggest that ADCC contributes to killing of CLL cells by anti-CD20 antibodies (rituximab and veltuzumab), whereas mAbs against CD22 (epratuzumab) and CD23 (lumiliximab) showed minimal ADCC. The magnitude of anti-CD20 mediated ADCC did not correlate with antigen density of CD20. ADCC was not influenced by the FcR genotype expressed by autologous NK cells. Allogeneic NK cells were superior to autologous NK cells in killing primary CLL cells.
Subject(s)
Antibodies, Monoclonal/immunology , Antibody-Dependent Cell Cytotoxicity , Antineoplastic Agents/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Receptors, IgG/immunology , Antibodies, Monoclonal, Humanized , Antibodies, Monoclonal, Murine-Derived , Antigens, CD/immunology , Antigens, CD20/immunology , Antigens, Neoplasm/immunology , CD52 Antigen , Cell Line, Tumor/immunology , Genotype , Glycoproteins/immunology , Humans , In Vitro Techniques , Killer Cells, Natural/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Middle Aged , Receptors, IgG/genetics , Recombinant Fusion Proteins/immunology , Rituximab , Sialic Acid Binding Ig-like Lectin 2/immunology , TransfectionABSTRACT
Chemotherapy used to treat lymphoma can cause severe neutropenia. Risk models have identified factors that predict neutropenia across all chemotherapy cycles. We used clinical information obtained during pretreatment evaluation to develop a predictive model for severe neutropenia in the first cycle of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy. This case series study included lymphoma patients receiving CHOP chemotherapy with or without rituximab who did not receive pre-emptive hematopoietic growth factor. Risk factors for neutropenia were identified from previously published models and included age >or=65 years, hypoalbuminemia, renal/cardiovascular disease, anemia, abnormal bone marrow and increased lactate dehydrogenase (LDH). A composite score equal to the number of pretreatment risk factors was used to predict severe neutropenia in cycle 1. Fifty-three percent of patients (47 of 89) had severe neutropenia, with 70% of first episodes occurring during cycle 1. Eighty-two percent of first-cycle, severe neutropenia events occurred in patients >or=65-years-old. In univariate analysis, age >or=65 years and increased baseline LDH were significantly associated with increased risk for severe neutropenia in cycle 1. In logistic regression modeling, the probability of severe neutropenia in cycle 1 increased as the number of pretreatment risk factors increased, with a one-unit increase in risk score resulting in a 2.3-fold increase in severe neutropenia. The study results suggest that data obtained before initiating CHOP-based chemotherapy can be used to identify those patients who are at risk for severe neutropenia in cycle 1. If validated, our model could be used to identify patients who would benefit from early use of growth factors.
