Post-hematopoietic stem cell transplantation immune-mediated anemia: a literature review and novel therapeutics

Abstract

Anemia after allogeneic hematopoietic stem cell transplantation (HSCT) can be immune or non-immune mediated. Auto- or alloimmunity resulting from blood group incompatibility remains an important cause in post-HSCT immune-mediated anemia. ABO incompatibility is commonly encountered in HSCT and may lead to serious clinical complications, including acute hemolysis, pure red cell aplasia, and passenger lymphocyte syndrome. It remains controversial whether ABO incompatibility may affect HSCT outcomes, such as relapse, nonrelapse mortality, graft-versus-host disease, and survival. Non-ABO incompatibility is less frequently encountered but can have similar complications to ABO incompatibility, causing adverse clinical outcomes. It is crucial to identify the driving etiology of post-HSCT anemia in order to prevent and treat this condition. This requires a comprehensive understanding of the mechanism of anemia in blood group-incompatible HSCT and the temporal association between HSCT and anemia. In this review, we summarize the literature on post-HSCT immune-mediated anemia with a focus on ABO and non-ABO blood group incompatibility, describe the underlying mechanism of anemia, and outline preventive and treatment approaches.

Figure 1.

Pathophysiology and targeted therapy for post-HSCT immune-mediated anemia. Post-HSCT anemia is multifactorial as a result of new auto- or alloantibodies in combination with T cell– and cytokine-mediated inflammatory processes. There are no formal guidelines in management. Several therapeutic approaches that target different pathophysiologic aspects of post-HSCT immune-mediated anemia are outlined. DLI, donor lymphocyte infusion; IVIG, IV immunoglobulin; Syk, spleen tyrosine kinase.

Figure 2.

General approach for posttransplantation immune-mediated hemolysis. The graph outlines underlying mechanisms of posttransplantation hemolysis, timing posttransplantation, preventive methods, and treatment strategies. Note there is no consensus or guideline on how to manage posttransplantation immune-mediated anemia. The management approaches listed are based on expert opinions and available literature. AIHA, autoimmune hemolytic anemia; IVIG, IV immunoglobulin; TPO, thrombopoietin.

Figure 3.

PRCA. PRCA is more frequently encountered in major ABO mismatch during the first 1 to 3 months posttransplantation. Management approach is similar to PLS, with frequent monitoring and RBC transfusion support. Other pharmacologic interventions can be considered in refractory cases. CBC, complete blood count; Hb, hemoglobin; IVIG, IV immunoglobulin; TMA, thrombotic microangiopathy.

Figure 4.

PLS. Proactive approach with identifying patients at risk before transplantation, alerting the blood bank service, conducting frequent count monitoring, and providing transfusion support in the first 2 weeks posttransplantation is key for better clinical outcomes. Hb, hemoglobin; IVIG, IV immunoglobulin; TMA, thrombotic microangiopathy.