Aplastic Anemia as a Roadmap for Bone Marrow Failure: An Overview and a Clinical Workflow

Abstract

In recent years, it has become increasingly apparent that bone marrow (BM) failures and myeloid malignancy predisposition syndromes are characterized by a wide phenotypic spectrum and that these diseases must be considered in the differential diagnosis of children and adults with unexplained hematopoiesis defects. Clinically, hypocellular BM failure still represents a challenge in pathobiology-guided treatment. There are three fundamental topics that emerged from our review of the existing data. An exogenous stressor, an immune defect, and a constitutional genetic defect fuel a vicious cycle of hematopoietic stem cells, immune niches, and stroma compartments. A wide phenotypic spectrum exists for inherited and acquired BM failures and predispositions to myeloid malignancies. In order to effectively manage patients, it is crucial to establish the right diagnosis. New theragnostic windows can be revealed by exploring BM failure pathomechanisms.

Keywords: aplastic anemia; bone marrow failure; bone marrow immune-microenvironment; cytopenia; hematopoietic stem cells.

Figure 1

Schematic diagnostic approach to bone marrow failure. HLA: human leukocyte antigen, MDS: myelodysplastic syndromes; PNH: paroxysmal nocturnal hemoglobinuria.

Figure 2

The pathobiological landscape and a schematic overview of aplastic anemia.

Figure 3

Schematic treatment selection and follow-up in AA. CSA: cyclosporine. HSCT: hematopoietic stem cell transplant. HLA: human leukocyte antigen. IST: immunosuppressive therapy. MSD: HLA-matched sibling donors.