Alpha-thalassemia-myelodysplastic syndrome

Alpha-thalassemia-myelodysplastic syndrome (ATMDS), also known as acquired alpha-thalassemia myelodysplastic syndrome or alpha-thalassemia with myelodysplastic syndrome, is a rare acquired hematologic condition in which patients develop alpha-thalassemia (hemoglobin H disease) in the setting of a myelodysplastic syndrome (MDS). Unlike inherited forms of alpha-thalassemia, ATMDS arises from somatic mutations — most commonly in the ATRX gene (Xp13.3) — that occur in hematopoietic stem cells, leading to downregulation of alpha-globin gene expression. The condition predominantly affects older males and is characterized by the presence of hemoglobin H (HbH) inclusions in red blood cells alongside the typical features of MDS, including ineffective hematopoiesis, cytopenias, and dysplastic changes in the bone marrow. Clinically, patients present with a hypochromic microcytic anemia that is disproportionate to what would be expected from MDS alone, often accompanied by macrocytosis in other red cell populations, creating a dimorphic blood picture. Additional features include fatigue, pallor, and other symptoms related to anemia and bone marrow failure such as recurrent infections and bleeding tendencies. HbH inclusions can be detected on supravital staining of peripheral blood. The myelodysplastic component carries a risk of progression to acute myeloid leukemia. Treatment is directed at the underlying myelodysplastic syndrome and may include supportive care with red blood cell transfusions, erythropoiesis-stimulating agents, hypomethylating agents (such as azacitidine or decitabine), and in selected patients, allogeneic hematopoietic stem cell transplantation. Management of the alpha-thalassemia component is generally supportive. Prognosis depends largely on the MDS subtype and risk category.

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