Orelabrutinib in the treatment of pure red cell aplasia after allogeneic hematopoietic stem cell transplantation

Abstract Background:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) currently represents the only curative treatment for patients with acute myeloid leukemia. Among allo-HSCT recipients, ABO blood group incompatibility occurs in 30% to 50% of donor-recipient pairs. This incompatibility can lead to the persistence of recipient antibodies against donor red blood cells (anti-donor antibodies), potentially resulting in delayed erythroid reconstitution lasting for months and the development of post-transplant pure red cell aplasia (PRCA). Reported therapeutic strategies for post-transplant PRCA include Rituximab, Bortezomib, Cyclosporine A, Glucocorticoid, Cyclophosphamide, Daratumumab, and erythropoietin. Case Summary: A 58-year-old female with acute myeloid leukemia underwent an 8/12 HLA-matched haploidentical allogeneic hematopoietic stem cell transplantation in April 2023. The donor (blood group A Rh+) and recipient (blood group O Rh+) had major ABO incompatibility. On day +53 post-transplantation, the patient developed PRCA. After failure of sequential therapies—including Rituximab, Bortezomib, Cyclosporine A with Glucocorticoid, Cyclophosphamide, and Daratumumab—treatment was switched to Orelabrutinib (150 mg once daily). This intervention elicited a reticulocyte response, followed by gradual achievement of transfusion independence. Conclusion: Orelabrutinib has demonstrated both safety and efficacy in eliminating autoantibodies targeting erythroid precursor cells. Thus, it represents a viable therapeutic option for refractory post-transplant PRCA following ABO-incompatible allo-HSCT.