Ten Years of Clinical Experience With Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation in the phosphatidylinositol glycan class A, X-linked gene, responsible for a deficiency in glycosyl phosphatidylinositol-anchored proteins. The absence of one of the glycosyl phosphatidylinositol-anchored protein complement regulatory proteins (CD59) leads to hemolysis. Clinical manifestations include chronic hemolysis, thromboembolic disease, infectious complications, chronic kidney injury, pulmonary hypertension, and smooth muscle dysfunction. (Source: Seminars in Hematology)
Source: Seminars in Hematology - April 9, 2018 Category: Hematology Authors: Flore Sicre de Fontbrune, R égis Peffault de Latour Tags: Research Article Source Type: research
Complement activation and inhibition in autoimmune hemolytic anemia: Focus on cold agglutinin disease
The classical complement pathway and, to some extent, the terminal pathway, are involved in the immune pathogenesis of autoimmune hemolytic anemia (AIHA). In primary cold agglutinin disease (CAD), secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, the hemolytic process is entirely complement-dependent. Complement activation also plays an important pathogenetic role in some warm-antibody AIHAs, especially when IgM is involved. This review describes the complement-mediated hemolysis in AIHA with a major focus on CAD, in which activation of the classical pathway is essential and particularly relevant for c...
Source: Seminars in Hematology - April 9, 2018 Category: Hematology Authors: Sigbj ørn Berentsen Source Type: research
Ten years of clinical experience with eculizumab in PNH patients
Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation in the phosphatidylinositol glycan class A (PIG-A), X-linked gene, responsible for a deficiency in glycosyl phosphatidylinositol-anchored proteins (GPI-APs). The absence of one of the GPI-AP complement regulatory proteins (CD59) leads to hemolysis. Clinical manifestations include chronic hemolysis, thromboembolic disease, infectious complications, chronic kidney injury, pulmonary hypertension and smooth muscle dysfunction. Until 10 years ago, treatment was mainly supportive, with most patients suffering from significant morbidity and shortened surviva...
Source: Seminars in Hematology - April 9, 2018 Category: Hematology Authors: Flore Sicre de Fontbrune, R égis Peffault de Latour Source Type: research
Complement activation and inhibition in autoimmune hemolytic anemia: Focus on cold agglutinin disease
The classical complement pathway and, to some extent, the terminal pathway, are involved in the immune pathogenesis of autoimmune hemolytic anemia (AIHA). In primary cold agglutinin disease (CAD), secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, the hemolytic process is entirely complement-dependent. Complement activation also plays an important pathogenetic role in some warm-antibody AIHAs, especially when IgM is involved. This review describes the complement-mediated hemolysis in AIHA with a major focus on CAD, in which activation of the classical pathway is essential and particularly relevant for c...
Source: Seminars in Hematology - April 9, 2018 Category: Hematology Authors: Sigbj ørn Berentsen Source Type: research
Ten years of clinical experience with eculizumab in PNH patients
Paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation in the phosphatidylinositol glycan class A (PIG-A), X-linked gene, responsible for a deficiency in glycosyl phosphatidylinositol-anchored proteins (GPI-APs). The absence of one of the GPI-AP complement regulatory proteins (CD59) leads to hemolysis. Clinical manifestations include chronic hemolysis, thromboembolic disease, infectious complications, chronic kidney injury, pulmonary hypertension and smooth muscle dysfunction. Until 10 years ago, treatment was mainly supportive, with most patients suffering from significant morbidity and shortened surviva...
Source: Seminars in Hematology - April 9, 2018 Category: Hematology Authors: Flore Sicre de Fontbrune, R égis Peffault de Latour Source Type: research
outside front cover, PMS 8883 metallic AND 4/C
(Source: Seminars in Hematology)
Source: Seminars in Hematology - April 1, 2018 Category: Hematology Source Type: research
MRD Testing in Multiple Myeloma: From a Surrogate Marker of Clinical Outcomes to an Every-Day Clinical Tool
Minimal residual disease (MRD) testing in multiple myeloma is here to stay. Studies show that MRD negativity is consistently associated with longer progression-free survival (PFS). It is just a matter of time until MRD negativity will become a regulatory endpoint for drug approval. Until that can happen, more analysis will be required to define the exact details of MRD in the regulatory setting. For example, for randomized studies there is need to define the amount of improvement in MRD negativity between the experimental arm and the control arm at a given time-point for a drug to obtain regulatory accelerated approval. (S...
Source: Seminars in Hematology - March 15, 2018 Category: Hematology Authors: Ola Landgren Tags: Disease Monitoring in Myeloma Source Type: research
MRD testing in multiple myeloma: From a surrogate marker of clinical outcomes to an every-day clinical tool
Minimal residual disease (MRD) testing in multiple myeloma is here to stay. Studies show that MRD negativity is consistently associated with longer progression-free survival (PFS). It is just a matter of time until MRD negativity will become a regulatory end-point for drug approval. Until that can happen, more analysis will be required to define the exact details of MRD in the regulatory setting. For example, for randomized studies there is need to define the amount of improvement in MRD negativity between the experimental arm and the control arm at a given time-point for a drug to obtain regulatory accelerated approval. (...
Source: Seminars in Hematology - March 15, 2018 Category: Hematology Authors: Ola Landgren Tags: 55/2 Disease Monitoring in Myeloma Source Type: research
Minimal Residual Disease Detection by Flow Cytometry in Multiple Myeloma: Why and How?
The outlook for myeloma patients has steadily improved with the introduction of newer drug combinations in recent years. Unlike older therapies that largely achieved only modest levels of neoplastic clone reduction, the newer drug combinations have led to deeper suppression of myeloma clones in most patients. Frequently the neoplastic clones become undetectable with traditional disease evaluation approaches. Recent studies using ultrasensitive disease monitoring have demonstrated that patients with disease undetectable by traditional techniques show wide heterogeneity in disease levels varying by several orders of magnitud...
Source: Seminars in Hematology - March 9, 2018 Category: Hematology Authors: Mikhail Roshal Tags: Review Source Type: research
Minimal Residual Disease Detection by Flow Cytometry in Multiple Myeloma; Why and How?
The outlook for myeloma patients has steadily improved with the introduction of newer drug combinations in recent years. Unlike older therapies that largely achieved only modest levels of neoplastic clone reduction, the newer drug combinations have led to deeper suppression of myeloma clones in most patients. Frequently the neoplastic clones become undetectable with traditional disease evaluation approaches. Recent studies using ultrasensitive disease monitoring have demonstrated that patients with disease undetectable by traditional techniques show wide heterogeneity in disease levels varying by several orders of magnitud...
Source: Seminars in Hematology - March 9, 2018 Category: Hematology Authors: Mikhail Roshal Source Type: research
Circulating Tumour DNA for Detecting Minimal Residual Disease in Multiple Myeloma
Circulating tumor DNA faithfully recapitulates somatic mutations detected in bone marrow aspirates from patients with newly diagnosed or relapsed or recurrent myeloma. Extending these methods to enable detection of minimal residual disease will require increased sensitivity and breadth of genomic assays to maximize information content from small quantities of cell-free DNA; as well as definition of a clinically meaningful ctDNA concentration in comparison with conventional bone marrow cell-count thresholds. (Source: Seminars in Hematology)
Source: Seminars in Hematology - March 7, 2018 Category: Hematology Authors: Trevor J. Pugh Source Type: research
Circulating tumour DNA for detecting minimal residual disease in multiple myeloma
Circulating tumour DNA faithfully recapitulates somatic mutations detected in bone marrow aspirates from patients with newly diagnosed or relapsed/recurrent myeloma. Extending these methods to enable detection of minimal residual disease will require increased sensitivity and breadth of genomic assays to maximize information content from small quantities of cell-free DNA; as well as definition of a clinically-meaningful ctDNA concentration in comparison with conventional bone marrow cell-count thresholds. (Source: Seminars in Hematology)
Source: Seminars in Hematology - March 7, 2018 Category: Hematology Authors: Trevor J. Pugh Tags: 55/2 Disease Monitoring in Myeloma Source Type: research
Functional Imaging Methods for Assessment of Minimal Residual Disease in Multiple Myeloma: Current Status and Novel ImmunoPET Based Methods
Imaging plays a key role in assessment of myeloma. Osteolytic bone lesions are optimally assessed using structural imaging, however the structural changes lag the functional changes in the disease. Functional imaging with fluoro deoxy glucose (FDG) positron emission tomography (PET) computerized tomography (CT) is useful in assessment of high-risk myeloma. FDG PET provides prognostic information and is helpful in monitoring response to therapy. However, it is nonspecific and may not be optimal in assessing treatment response to immunotherapeutic agents. (Source: Seminars in Hematology)
Source: Seminars in Hematology - March 5, 2018 Category: Hematology Authors: Neeta Pandit-Taskar Tags: Review Source Type: research
MRD Testing in Multiple Myeloma: The Main Future Driver for Modern Tailored Treatment
The past decade, several highly efficacious drugs have been approved for the treatment of multiple myeloma. Many of these newer drugs are less toxic than older chemotherapy drugs. Using modern combination therapy in newly diagnosed multiple myeloma patients, high proportions of newly diagnosed multiple myeloma patients obtain minimal residual disease (MRD) negativity and MRD testing has rapidly become an integral part of clinical trials focusing on patients in this setting. Only recently, MRD negativity was reported in clinical trials focusing on older newly diagnosed multiple myeloma patients (ie, nontransplant candidates...
Source: Seminars in Hematology - March 5, 2018 Category: Hematology Authors: Ola Landgren, Sydney X. Lu, Malin Hultcrantz Tags: Review Source Type: research
