Pure red-cell aplasia following major and bi-directional ABO-incompatible allogeneic stem-cell transplantation: recovery of donor-derived erythropoiesis after long-term treatment using different therapeutic strategies.

Blood group incompatibility between donor and recipient of allogeneic stem cell transplants may be associated with post-transplant erythroid aplasia. A total of 548 patients (pts) received allogeneic transplant for malignant and non-malignant hematologic disorders. In a retrospective analysis, the prevalence and outcome of pure red-cell aplasia (PRCA) in 44 pts with major and bi-directional ABO-mismatch were investigated. Bone marrow grafts were major ABO incompatible in 30 pts; there was bi-directional mismatch in the remaining 14 pts. The median number of transplanted mononuclear cells (NC) was 4.74 x 10(8)/kg (range 0.1-26.4) including CD34+ cells, 3.02 x 10(6)/kg (range 0.9-21.7). Granulocyte engraftment >0.5 x 10e9/l occurred after a median of 21 days (7-32), and platelet exceeded >50 x 10e9/l after a median of 23.5 days (12-109). Acute and chronic graft vs host disease (GVHD) developed in 23 (52%) and 26 (59%) of the patients, respectively. Six (13%) patients transplanted with major and bi-directional ABO-incompatibility developed PRCA. The treatment of PRCA consisted of plasmapheresis (PEX), rapid cyclosporine (CsA) discontinuation, donor lymphocyte infusions (DLI), erythropoietin (EPO), azathioprine, and rituximab. The therapy resulted in erythroid recovery in five out of six patients after a median of 13 months (range 3-16). The median number of transfused red blood cells (RBCs) was 36 U (range 8-57). With a median follow-up of 37 months, the 5-year probability of overall survival (OS) for the PRCA group was 66%. Major ABO mismatch may lead to delayed donor erythroid engraftment. It results in long-term transfusion dependence and, therefore, the risk of iron overload. The therapy is long lasting, but usually effective in majority of patients.

Successful treatment of pure red cell aplasia with repeated, low doses of rituximab in two patients after ABO-incompatible allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia.

We describe two patients with acute myeloid leukemia successfully treated with anti-CD20 antibody for pure red cell aplasia (PRCA) following ABO-mismatched allogeneic hematopoietic stem cell transplantation (HSCT). PRCA following HSCT is associated with major ABO incompatibility between donor and recipient and is due to an inhibition of donor erythroid precursors by residual host isoagglutinins. The first patient developed PRCA resistant to several treatment options including donor-derived leukocyte infusions (DLI), high-dose erythropoietin (EPO), and rapid tapering of cyclosporin A (CsA). This patient also received anti-viral therapy as CMV and parvovirus B19 infections were regarded as additional causes of PRCA. Due to a loss of donor chimerism, he underwent second HSCT, but PRCA still persisted. He showed no evidence of graft-versus-host disease (GVHD). Finally he was administered anti-CD20 antibody (rituximab) at a dose of 150/m2 and PRCA resolved in a short period of time. The case was complicated by life-threatening pulmonary aspergillosis with septic shock, successfully treated with anti-fungal therapy. The second case concerns a patient, who revealed PRCA after major ABO-incompatible HSCT from his brother. Considering our experience with the previously described patient, he proceeded to rituximab at a dose of 150/m2 as first line treatment. We observed rapid recovery from PRCA without any side effects. We conclude that rituximab seems to be a promising therapeutic option in patients with PRCA after ABO-mismatched HSCT, in whom conventional treatment fails.