Pure red cell aplasia with the onset of graft versus host disease

Abstract

Summary:Pure red cell aplasia (PRCA) occurred in the fourth month after an ABO-compatible nonmyeloablative allograft coincident with the cessation of immunosuppression and the onset of limited chronic GVHD. No secondary causes could be identified. Erythropoiesis was restored promptly and durably with the resumption of immunosuppression. A clonal T cell receptor c rearrangement was detected in peripheral blood lymphocytes prior to the onset of PRCA. PRCA should be added to the list of immunohaematological complications of GVHD. Bone Marrow Transplantation (2003) 32, 1099-1101. doi:10.1038/sj.bmt.1704271 Keywords: pure red cell aplasia; GVHD Pure red cell aplasia (PRCA) is most commonly an idiopathic disorder, although secondary causes such as lymphoproliferative and myelodysplastic disorders, parvovirus infection and thymoma are well recognised. 1 Post transplant, PRCA is usually a complication of major ABO incompatibility and may have an increased incidence after nonmyeloablative compared with myeloablative conditioning regimens. 2 While autoimmune haematological disorders including haemolytic anaemia and immune neutropenia, thrombocytopenia and pancytopenia due to peripheral destruction are well recognised post allograft, 3 often in the context of chronic graft versus host disease (GVHD), 4 to our knowledge PRCA as an immune complication in the absence of ABO incompatibility has not been reported. This case documents PRCA after an ABO-compatible nonmyeloablative allograft in the absence of any secondary causes. The onset was coincident with the early onset of chronic GVHD and it resolved promptly after the recommencement of immunosuppression. Case reportA 48-year-old man underwent a peripheral blood progenitor cell, ABO-matched sibling allograft in May 2002 for transformed low-grade non-Hodgkin's lymphoma relapsing after an autograft 11 months previously. A reducedintensity conditioning regimen (fludarabine 25 mg/m 2 day 6 to day 2, cyclophosphamide 1 g/m 2 day 3 to day 2) was used with cyclosporin A 3 mg/kg i.v. and short course methotrexate as GVHD prophylaxis. White cell recovery occurred early in the second week post transplant (neutrophils 40.5 Â 10 9 /l by day 10). Mild early cutaneous acute GVHD was observed requiring low-dose steroid therapy. Both cyclosporin A and prednisolone were tapered from day 60 and stopped by day 100. Table 1 details the haemoglobin (Hb) levels, marrow findings, chimerism results, immunosuppressive medication and GVHD status at various time points post transplant. Hb levels were stable around 120 g/l without transfusion by day 95, but fell thereafter by approximately 1 g/week to a nadir of 78 g/l by day 120. There was no history of blood loss. Red cell aplasia, confirmed by glycophorin immunohistochemistry, was demonstrated on a day 100 marrow aspirate ( Figure 1a). No B cell lymphoma was demonstrated by morphology or flow cytometry. The majority of marrow lymphocytes were suppressor T cells with a CD4:CD8 ratio of 0.5. An excess of large granular lymphocytes was not seen in the...

Prevention of pure red cell aplasia after major or bidirectional ABO blood group incompatible hematopoietic stem cell transplantation by pretransplant reduction of host anti-donor isoagglutinins

“…Moreover, although several case reports suggested such an association, it was not confirmed by any of the case series. 30,49 In support of the findings of Mielcarek et al, we observed that both the occurrence of acute GvHD and isoagglutinin reduction were associated with a shorter time to RBC engraftment in patients with major ABO incompatible HSCT. In contrast, faster RBC engraftment in patients who underwent GvHD was not observed after ABOidentical HSCT (data not shown).…”

“…25 Major ABO-incompatibility was the most common risk factor described in 120 patients, bidirectional ABO incompatibility was found in 5 patients. 16,25,37 Two of the remaining three patients developed PRCA after ABO compatible HSCT 41,49 and one after autologous HSCT. 39 No clear explanation was found for the PRCA in these patients.…”

“…48,49 If this strategy is not successful, several other strategies have been proposed according to the pathophysiology of the disorder: plasmapheresis, 43,46,64 antithymocyte globulin, 38,41 erythropoietin, 39,42,44,61 corticosteroids, 53,56 rituximab, 47,54 and donorlymphocyte infusions to induce GvHD. 45,51 Virtually all of these treatments have only been evaluated in a few patients or in single case reports.…”

Evidence for ineffective erythropoiesis in severe sickle cell disease

“…Previous studies have documented that donor antibodies can target recipient RBC antigens, especially in cases of ABO incompatibility, and that this can result in selective hemolysis of recipient RBC and RBC precursors. 15,16 GVHD can also target recipient hematopoietic stem cells. [17][18][19][20][21] However, none of the patients in this report had evidence of immune-mediated hemolysis despite the presence of ABO incompatibilities in 6 of the 8 patients.…”

Successful therapy of chronic graft-versus-host disease manifesting as pure red cell aplasia with single-agent rituximab

“…Nonetheless, PRCA can occur as a manifestation of cGVHD specifically. 1,4 Furthermore, A/O donor/recipientmismatch has been associated with a particular increase in the risk of development of PRCA post PBSCT. 5 A growing body of literature supports a role for rituximab as a therapy for cGVHD.…”