Pure red cell aplasia (PRCA) is a challenging complication post ABO-mismatched allogeneic stem-cell transplantation (allo-HSCT) that renders the patient transfusion-dependent. Several treatment options have been suggested in the literature; however, there is no standard treatment of choice. Here we present a case of PRCA post ABO-mismatched allo-HSCT successfully treated with daratumumab after failure of rituximab treatment.
Case Report:
A 37-year-old male diagnosed with alpha/beta hepato-splenic T- cell lymphoma. He received three cycles of ICE regimen (Ifosfamide, Carboplatin, Etoposide), followed by splenectomy, after which he achieved complete remission. The patient then received conditioning with fludarabine 40 mg/m2 IV daily for 4 days and 200 cGy twice a day total body irradiation (TBI) for 3 days. He received peripheral blood stem cell transplantation from his haploidentical brother with a CD34+ cell dose of 6.3 x106 25 /kg. The donor blood group was A Rh-positive and the recipient was O Rh-positive. ABO antibodies titer of the recipient showed anti-A IgG and IgM of 1:1024 and 1:512, respectively. The stem cell product was plasma depleted with RBC content of 2.8 ml in the graft. For prophylaxis against graft versus host disease, cyclosporine, mycophenolate mofetil and post-transplantation cyclophosphamide were administered.
Post-transplantation course was complicated by cytomegalovirus (CMV) reactivation and mastoiditis, which was managed according to the local guidelines. Engraftment was prompt, with neutrophils recovery on day +15 and platelets recovery on day +17. Bone marrow and peripheral blood chimerism studies showed >95% of donor cells DNA on day +28. Bone marrow biopsy showed no evidence of disease; however, it demonstrated a marked decrease in erythropoiesis and reticulocytopenia. His reticulocytes count continued to decline. From day +60, he started to require red cell transfusion every 5-7 days. Bone marrow biopsy results showed hypocellular bone marrow with persistent pure red cell aplasia. The patient was diagnosed with PRCA. Starting from day +120, four doses of weekly rituximab 375 mg/m2 were given; however, the patient remained transfusion-dependent, with severe reticulocytopenia. Tapering of immunosuppressive therapy with cyclosporine was started on day +134 with discontinuation on day +200; yet the patient continued to require frequent red blood cell transfusions. After careful evaluation of the risks and benefits, daratumumab was initiated, on day +183 post-transplantation, at a dose of 16 mg/kg once per week for a total of 6 weeks. Daratumumab infusion was well tolerated except for mild infusion related reaction during the first dose administration. Cyclosporine was discontinued on day +200. After receiving six doses of daratumumab, his response was suboptimal therefore two additional doses were given. The patient showed a significant reticulocyte response and consecutively became transfusion independent. Anti-A titer has progressively decreased to an undetectable level.
Pure red cell aplasia is a known complication post-HSCT occurring in 8-26% of major ABO-mismatched HSCT [6]. Major ABO incompatibility is caused by recipient isohemagglutinins directed against donor RBCs, which later inhibit the proliferation and growth of early erythroid stages [2,3]. PRCA is characterized by transfusion-dependent anemia, reticulocytopenia, and severe erythroid hypoplasia in the bone marrow. Spontaneous remission can occur approximately 60 days post-transplantation, evident by residing titers, which is unlikely beyond this period
Plasma cells are a potential target for therapy because they may contribute to antibody production, especially in refractory hemolytic anemia and PRCA. Compared with other plasma cell targeted therapy, Daratumumab has a more appealing safety profile and mechanism of action Daratumumab, a human IgG1κ monoclonal antibody targeting CD38 used in the treatment of multiple myeloma, was found to have promising outcomes for the treatment of PRCA . It is thought to eliminate the pathogenic plasma-cell population and overcome the refractory pure red-cell aplasia. The use of anti-CD38 therapy with daratumumab to target residual host plasma cells is safe and effective, and it can be considered in refractory recipients with PRCA after allo-HSCT secondary to ABO incompatibility.
No relevant conflicts of interest to declare.
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