Strategies for managing transfusional iron overload: conventional treatments and novel strategies
Purpose of review
For individuals who have transfusion-dependent anemia, iron overload is the long-term complication, which results in significant morbidity. Ameliorating this is now the biggest unmet need. This review specifically addresses this issue.
Recent findings
Over the last decade or so, major advances in the treatment of these individuals, has resulted from novel strategies aimed at reducing transfusion requirement as well as optimizing chelation therapy. This review will summarize these advances and provide insights into some of the therapies in the pipeline. Strategies aimed at reducing transfusion require...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research
Pain and sickle cell disease
Purpose of review
Pain is a major comorbidity of sickle cell disease (SCD). Opioids are the mainstay for pain treatment but remain suboptimal. We discuss mechanism-based treatable targets devoid of opioids to prevent and/or treat SCD pain.
Recent findings
Understanding the pathogenesis of pain is critical to develop targeted therapies. Nevertheless, acute and chronic pain can have independent and/or overlapping mechanisms. The origin of pain involves neurovascular and neuroimmune interactions from the periphery and/or central nervous system. Immunomodulatory components of acute and/or chronic sickle pain for targeting...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research
New insights into the links between hypoxia and iron homeostasis
Purpose of review
This review outlines recent discoveries on the crosstalk between oxygen metabolism and iron homeostasis, focusing on the role of HIF-2 (hypoxia inducible factor-2) in the regulation of iron metabolism under physiopathological conditions.
Recent findings
The importance of the hepcidin/ferroportin axis in the modulation of intestinal HIF-2 to regulate iron absorption has been recently highlighted. Latest advances also reveal a direct titration of the bone morphogenetic proteins by the erythroferrone contributing to liver hepcidin suppression to increase iron availability. Iron is recycled thanks to ery...
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: ERYTHROID SYSTEM AND ITS DISEASES: Edited by Narla Mohandas Source Type: research
Editorial introductions
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - April 4, 2019 Category: Hematology Tags: EDITORIAL INTRODUCTIONS Source Type: research
Novel tyrosine kinase inhibitors for patients with inadequate response in chronic myeloid leukemia
Purpose of review
The purpose of this review is to summarize treatment expectations and response milestones, to conceptualize the approach to defining inadequate response to therapy and critically appraise current available strategies, as well to highlight novel agents under development to address unmet needs in chronic myeloid leukemia (CML) therapy.
Recent findings
Given excess risk with currently available highly potent ABL1 (Abelson murine leukemia viral oncogene homolog 1) inhibitors, a number of alternate, highly potent compounds have entered the clinic to address select resistance such as the T315I mutation wit...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Novel Approaches for Systemic Mastocytosis
Purpose of review
The purpose of this review is to summarize the pathophysiology of systemic mastocytosis, review the most recent clinical trials and drug development in systemic mastocytosis, with a specific focus on the advanced systemic mastocytosis subtypes.
Recent findings
Systemic mastocytosis is a clonal neoplasm of mast cells that has had a number of successful therapeutic options being developed in the past few years. The first therapeutic agent to be Food and Drug Administration (FDA) approved in decades was midostaurin in 2017 with a 60% response rate % with improvement in both end-organ damage and symptoms...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Posttransplant maintenance therapy for acute leukemias
Purpose of review
Allogeneic hematopoietic stem cell transplantation cures a significant proportion of patients with hematological malignancies. Unfortunately, leukemia recurrence is the main cause of transplant failure. Risk factors for relapse include presence of minimal residual disease and a variety of well-recognized leukemia prognostic factors. Posttransplant therapy could decrease the risk of leukemia relapse and is under investigation. In this review, we summarize the current research in maintenance therapy for the prevention of acute leukemia recurrence after allogeneic transplant.
Recent findings
Epigenetic ...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Progress in the problem of relapsed or refractory acute myeloid leukemia
Purpose of review
The majority of patients with acute myeloid leukemia (AML) die from disease recurrence and historically, treatment options in both the relapsed and refractory settings of this disease have been limited. However, new insights into the molecular characterization and biology of relapsed and refractory AML have led to novel therapeutics and improvement in outcomes in these settings. The current understanding of mechanisms of disease resistance and status of treatment options both currently available and under exploration in relapsed and refractory AML are summarized in this review.
Recent findings
The ra...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
What are the most promising new agents in myelodysplastic syndromes?
Purpose of review
Myelodysplastic syndromes (MDS) are a diverse group of clonal disorders of hematopoietic stem or progenitor cells that represent the most common class of acquired bone marrow failure syndromes in adults. Despite significant improvement in the pathologic insight into this group of disorders, therapeutic options remain limited and allogeneic hematopoietic stem-cell transplantation is the only treatment that can induce long-term remission in patients with MDS. The goals of therapy for MDS are based on disease prognostication, with a focus of minimizing transfusion dependence and preserving quality of life ...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Why are hypomethylating agents or low-dose cytarabine and venetoclax so effective?
Purpose of review
Venetoclax with backbone therapies have shown promising efficacy for newly diagnosed, previously untreated, older, unfit acute myeloid leukemia patients. This review discusses this data and potential reasons for the efficacy of these venetoclax-based combinations.
Recent findings
Venetoclax with hypomethylators and low-dose cytarabine have resulted in high response rates, promising response durations, and significant overall survival in relatively small, uncontrolled studies. There is emerging data that these responses are due to the effective targeting of leukemia stem cells through an alteration of...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Outpatient induction and consolidation care strategies in acute myeloid leukemia
Purpose of review
Patients with acute myeloid leukemia (AML) are almost invariably kept in the hospital until resolution of cytopenias following intensive induction chemotherapy. This care approach is costly and may further contribute to the reduced qualify of life of these patients. This has raised interest in moving at least part of this care to the outpatient setting. Reimbursement challenges for inpatient administration of some of the new drugs approved for AML in the last 2 years adds to this interest.
Recent findings
Retrospective and smaller prospective studies have shown that outpatient management following in...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Which patients with acute myeloid leukemia in CR1 can be spared an allogeneic transplant?
Purpose of review
Disease relapse remains the major cause of treatment failure in adults with acute myeloid leukemia (AML) in first complete remission (CR1) treated with intensive chemotherapy alone. Allogeneic stem cell transplantation (allo-SCT) reduces the risk of disease recurrence, and thus the advent of reduced intensity-conditioning regimens coupled with increased donor availability has increased the deliverability of potentially curative transplant therapy in AML. However, allo-SCT remains associated with significant additional morbidity and mortality, and it is therefore important to identify patients whose outc...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Shifting therapeutic paradigms in induction and consolidation for older adults with acute myeloid leukemia
Purpose of review
As the age and life expectancy of the general population rise, the number of acute myeloid leukemia (AML) patients suitable for therapy is expected to dramatically increase. The population of older adults with AML, while already comprising the vast majority of AML patients, has not been specifically addressed in terms of unique age-related features, such as existence of comorbidities, frailty, and disease biology.
Recent findings
Over the past decade, major improvements in the approach to the management of older adults with AML included: incorporation of new comorbidity scores specifically oriented t...
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
Editorial introduction
No abstract available (Source: Current Opinion in Hematology)
Source: Current Opinion in Hematology - February 1, 2019 Category: Hematology Tags: EDITORIAL INTRODUCTION Source Type: research
Cell biology of activated protein C
Purpose of review
The serine protease activated protein C (aPC) was initially characterized as an endogenous anticoagulant, but in addition conveys anti-inflammatory, barrier-protective, and pro cell-survival functions. Its endogenous anticoagulant function hampered the successful and continuous implantation of aPC as a therapeutic agent in septic patients. However, it became increasingly apparent that aPC controls cellular function largely independent of its anticoagulant effects through cell-specific and context-specific receptor complexes and intracellular signaling pathways. The purpose of this review is to outline t...
Source: Current Opinion in Hematology - November 28, 2018 Category: Hematology Tags: SPECIAL COMMENTARY Source Type: research
