Biology and clinical management of hypoplastic MDS: MDS as a bone marrow failure syndrome

Hypoplastic MDS is a subset of MDS characterized by marrow hypocellularity diagnosed in 10–15% of MDS patients. The pathogenesis of this disease shares features of aplastic anemia with activation of the effector T cells against hematopoietic stem and progenitor cells and high-risk MDS with acquisition of somatic mutations that provide survival and growth advantage of these cells in the inflammatory bone marrow microenvironment. Clonal evolution in hypoplastic MDS may be associated with accumulation of DNA damage and progression to AML while clonal hematopoiesis in aplastic anemia is strongly related to immune escape of the hematopoietic cells. Distinction of hypoplastic MDS from other acquired and inherited bone marrow failure syndromes is frequently challenging but it is critical for the appropriate clinical management of the patients. Treatment with immunosuppression is an important component of the clinical approach to patients with hypoplastic MDS while hypomethylating agents and early allogeneic bone marrow transplantation are also considerations in some patients. In this review, we summarize the current literature on the biology of hypoplastic MDS, the differences between this disease and other bone marrow failure syndromes, and the treatment algorithm for patients with this subtype of MDS.