Migdady and colleagues conducted a literature review on immune-mediated anemia occurring after hematopoietic stem cell transplantation (HCT) and presented their findings in a study published in Blood Advances.

“Auto- or alloimmunity against the RBC [red blood cell] are an important etiology of immune-mediated anemia in blood group mismatched HCT,” they wrote.

“The source of auto- or alloimmunity may be donor or recipient, such as passive antibody transfusion, passenger lymphocyte syndrome, alloantibodies formed against engrafting hematopoietic cells, or new auto- or alloantibodies due to transfusions.”

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In addition to blood group mismatch causing immune-mediated anemia, another possible cause is autoimmunity. Studies indicate that autoimmune hemolytic anemia (AIHA), of which cold agglutinin disease (CAD) is a subtype, occurs in around 4% to 6% of HCT recipients.

One study investigating T-cell depleted haploidentical HCT in patients with severe combined immunodeficiency demonstrated an AIHA incidence of 19.5%. In addition, medical researchers discovered that patients are more likely to develop AIHA after the second HCT as opposed to after the first HCT.

Read more about CAD etiology 

“The pathophysiology of AIHA post-HCT has not been fully elucidated, but may be related to formed autoantibodies and dysregulated immune tolerance,” Migdady et al wrote. The profile of a patient who has developed AIHA post-HCT is usually 1 who is severely lymphopenic with a deficiency, particularly in regulatory T-cells. 

What are some therapies for treating post-HCT immune-mediated anemia? Mild to moderate cases are normally self-limited and can be treated with simple transfusions of antigen-negative RBCs. Other therapeutic strategies are mainly derived from existing AIHA treatments.

“Based on mechanism of action, the options can be categorized into immunosuppression, which include the use of systemic steroids, [intravenous immune globulin], rituximab, cyclophosphamide, azathioprine, and splenectomy in the severe cases, immunoabsorption, RBC or plasma exchange, and stimulation of erythropoiesis using erythropoietin or thrombopoietin,” the authors concluded.


Migdady Y, Pang Y, Kalsi SS, Childs RW, Arai S. Post-hematopoietic stem cell transplantation immune-mediated anemia: a literature review and novel therapeutics. Blood Adv. Published online December 31, 2021. doi:10.1182/bloodadvances.2021006279