Border between aplastic anemia and myelodysplastic syndrome

Abstract

Distinguishing between acquired aplastic anemia (AA) and myelodysplastic syndrome (MDS) with a low blast cell percentage is often difficult and problematic, as both diseases are syndromes primarily defined by morphological findings, and their diagnostic criteria do not necessarily reflect the pathophysiology of their bone marrow (BM) failure. As a result, many patients with benign BM failure that should be managed as AA are diagnosed as having MDS, due to the absence of BM hypocellularity and the presence of dysplastic signs in the BM, and are treated inappropriately with toxic therapies, such as hypomethylating agents, and stem cell transplantation from unrelated donors. BM failure syndromes need to be managed in ways appropriate to their pathophysiology, which is more accurately determined by using markers such as the presence of glycosylphosphatidylinositol-anchored protein-deficient cells and HLA-A lacking leukocytes. We recently found that plasma thromobopoietin level is one of the most useful markers for distinguishing benign and pre-leukemic BM failure syndromes.

Global transcriptome analyses of human and murine terminal erythroid differentiation

“…[48][49][50] Another important use for these data sets is to develop a better mechanistic understanding of disordered erythropoiesis, with the ability to better understand stage-specific defects. This includes disorders such as the thalassemia syndromes, bone marrow failure syndromes and aplastic anemia [51][52][53][54][55][56] as well as acquired disorders such as the myelodysplasia syndromes, [57][58][59] particularly subtypes with disordered terminal erythroid differentiation. Numerous abnormalities have been identified in these disorders, including perturbed apoptosis, cytokine signaling, and regulation of cellular growth.…”

Are mild/moderate acquired idiopathic aplastic anaemia and low-risk myelodysplastic syndrome one or two diseases or both and how should it/they be treated?

“…16 However, this distinction can be critical because of therapy implications. For example, persons diagnosed as having mild/ moderate acquired idiopathic aplastic anaemia often receive immune suppression whereas persons diagnosed as having low-risk with MDS often receive hypo-methylating drugs.…”

“…The latter suppress bone marrow function ideally avoided in persons with a non-neoplastic bone marrow disorder. There are, of course, exceptions such as treating young persons with MDS with immune suppression; [15][16][17] responses are sometimes observed. However, most haematologists hesitate using anti-thymocyte globulin (ATG) in persons thought to have MDS because of the possibility of worsening bone marrow function and because of the absence of definitive evidence of improved survival.…”

Diagnostic problems in acquired bone marrow failure syndromes

“…This happens because dysplasia is commonly seen in the BM of AA patients with small populations of PNH-type cells, just like in the BM of PNH patients. In such cases, the BM is not consistently hypocellular, due to residual hot spots [6]. Although the detection of a hypocellular BM is a prerequisite for diagnosing AA, assessing BM cellularity in patients with BM failure can be difficult, particularly when the cytopenia is not severe.…”