Updates on the pathophysiology and treatment of aplastic anemia: a comprehensive review

Abstract

The past decade or longer has witnessed an acceleration in our understanding of previously developed immune system and clonal evolution mechanisms, and the genesis of more novel concepts of telomere attrition. Many of these concepts are steadily finding their way into translation in various aspects of clinical practice, and provide prospects to improve AA management and inform therapeutic strategy development. In this review, we intend to discuss the pathophysiology and treatments with an emphasis on most recent developments to provide an update on our understanding of disease mechanisms. Areas covered: A literature search was undertaken addressing various aspects of pathophysiology with a focus on the role of immune system repertoire, telomeres and mutational events surrounding AA. We also reviewed upon the temporal evolution of treatment strategies in AA to the contemporary management of today and commented briefly upon the more recently investigated novel therapies and their expanding niche especially in the transplant and salvage setting. Expert commentary: Immune-mediated destruction of hematopoietic stem and progenitor cells, leading to a marrow devoid of hematopoietic elements, and peripheral pancytopenia are the hallmarks of AA. Recent studies have shed light on another facet of the disease - as a clonal disorder characterized by karyotypic abnormalities, genomic instability, telomere attrition, and recurrent somatic mutations reminiscent of myeloid malignancies. Further understanding of this underlying pathophysiology can help in improving prognostication and treatment of this disease.

Keywords: Aplastic; alemtuzumab; antithymocyte globulin; clonal evolution; eltrombopag; immunosuppressive; telomere; transplant.