CD34+-enriched donor lymphocyte infusions in a case of pure red cell aplasia and late graft failure after major ABO-incompatible bone marrow transplantation

Abstract

Summary:A variety of immunohematological complications may occur after ABO-incompatible BMT. We report a CML patient (blood group O) who received a BMT from an HLA-identical sibling (blood group AB). The transplant was followed by normal myeloid and megakaryocytic engraftment, but erythroblastopenia persisted for more than 200 days after BMT. By bone marrow culture studies, a complement-dependent serum inhibitor of hemopoiesis was detected, suggesting immunological inhibition of erythropoiesis. The patient was resistant to a number of treatments such as intravenous gammaglobulins, prednisolone and high-dose erythropoietin. Full engraftment with normal blood counts and marrow cellularity was achieved after two dose-escalating CD34 + -enriched donor lymphocyte infusions (DLI). This experience suggests that CD34 + -enriched DLI may be an effective treatment for patients with delayed engraftment or late graft failure due to major ABOincompatibility. Keywords: PRCA; graft failure; DLI; CD34 + cells Allogeneic bone marrow transplant with major ABO incompatibility may be associated with delayed erythroid engraftment that may either regress spontaneously or become chronic. Acquired pure red cell aplasia (PRCA) has been reported after major ABO-incompatible transplant from peripheral blood 1 or marrow, 2 unmanipulated or T cell-depleted progenitor cells. It is characterized by severe anemia, reticulocytopenia and absence of erythroblasts in otherwise normally engrafted bone marrow. Although human parvovirus B19 may be a causative agent of PRCA following BMT, 3 more frequently autoimmune or alloimmune mechanisms have a role in its pathogenesis. 4 A wellrecognized mechanism of PRCA complicating major ABOincompatible BMT involves antibodies towards red cell precursors; 2 a T cell-mediated suppression of erythropoiesis has also been described. ABO-incompatible BMT is a difficult task; various immunosuppressive regimens, erythropoietin and plasmapheresis have been used with variable results. 2 Immunemediated mechanisms may also play a key role in the development of late graft failure. 5 Graft rescue by infusing peripheral blood stem cells (PBSC) may be an effective therapy for patients with early or late graft failure, 6 whereas donor lymphocyte infusions (DLI) have been primarily used for treating or preventing cytogenetic or early hematological CML relapse. 7 We report a case of PRCA followed by a progressive graft failure complicating an ABO-incompatible allogeneic BMT for CML in chronic phase, that was successfully treated with CD34 + -enriched DLI. Case reportA 20-year-old woman underwent BMT from her HLAidentical brother 6 months after the diagnosis of CML in chronic phase. We used the conditioning regimen BU/CY2; GVHD prophylaxis was carried out with CYA (2 mg/kg) and short-course methotrexate. As the donor's blood group was AB (Rh: CcDee; Kell positive) and the recipient's was O (Rh: CCDee; Kell negative), erythrocyte-depleted marrow containing 3.8 × 10 6 /kg CD34 + cells and 2.54 × 10 4 /kg CFU-GM was transplanted. E...

Delayed donor red cell chimerism and pure red cell aplasia following major ABO-incompatible nonmyeloablative hematopoietic stem cell transplantation

“…2,4,54 Other reports have documented resolution of PRCA after DLI. 55,56 In our study, discontinuation of CsA appeared sufficient to induce a graft-mediated immune effect against host cells involved in isohemagglutinin production, leading to resolution of PRCA. While such immune-based strategies appear effective, GHVD may also ensue.…”

Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia

“…Other investigators have reported stem cell boosts, 28 DLI, 29 or CD34 þ -enriched DLI 30 as an effective therapy for declining donor chimerism, poor graft function, or mixed chimerism. Anti-T cell therapy with ATG and CAMPATH proved ineffective at stabilizing mixed chimerism in patient 2.…”

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

“…Neutrophil engraftment was reached after 17 days (95%-CI [16][17][18][19] and platelet engraftment after 32 days (95%-CI 27-38) without differences between the groups (p=0.379 and p=0.364, respectively). As shown in Figure 1B, patients who underwent anti-donor isoagglutinin reduction had faster RBC engraftment (p<0.001).…”