Immune-Mediated Hematopoietic Failure after Allogeneic Hematopoietic Stem Cell Transplantation: A Common Cause of Late Graft Failure in Patients with Complete Donor Chimerism

Abstract

Late graft failure (LGF) without evidence of residual recipient cells is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-SCT) and often requires stem cell infusion from the same donor when the patient fails to respond to conventional therapies. We screened the peripheral blood (PB) of 14 patients who developed donor-type LGF at 2 to 132 months after allo-SCT for the presence of the markers for immune-mediated bone marrow (BM) failure. Increased glycosylphosphatidyl inositol-anchored protein-deficient (GPI-AP) leukocytes, which accounted for .009% to 0.147% of the total granulocytes, were detected in 5 patients (severe aplastic anemia, n = 2; follicular lymphoma, n = 1; acute lymphoblastic leukemia, n = 1; myelodysplastic syndromes; n = 1) and 4.7% to 81.2% HLA-allele-lacking leukocytes (HLA-LLs) were detected in 2 patients (acute myelogenous leukemia, n = 1; and myelodysplastic syndromes, n = 1). Three of the 5 patients with increased GPI-AP leukocytes were treated with antithymocyte globulin (ATG), and 2 patients achieved transfusion independence. These results suggest that immune mechanisms that are similar to acquired aplastic anemia underlie condition of approximately one-half of the patients with donor-type LGF, and that in patients with increased GPI-AP cells, donor-derived hematopoiesis may be restored by ATG therapy alone without donor stem cell infusion.

Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation

“…Furthermore, in patients with increased GPI-AP − cells, hematopoiesis may be restored by anti-thymocyte globulin (ATG) therapy alone without further donor stem-cell infusion, indicating immunosuppressive therapy should be considered in these patients. 64 Together, immune responses are more active in PGF patients, and the BM immune microenvironment might play an important role in PGF.…”

Domino donor lymphocyte infusion for secondary poor graft function after HLA‐mismatched allogeneic stem cell transplantation between HLA‐identical sibling pairs with congenital immunodeficiency

“…Poor graft function (PGF) is a major obstacle to successful allogeneic stem cell transplantation after achieving normal bone marrow function. The pathogenesis of PGF has not been well documented, and it is possible that the immune system damages the hematopoietic compartment via exposure to inflammatory cytokines during graft versus host disease (GvHD) or viral infection 1,2 . One successful approach to treat PGF is by donor lymphocyte infusion (DLI) 3 .…”

Acquired Aplastic Anemia

“…57 Although return to recipient hematopoiesis is the most common pattern in late graft failure, donor-derived recurrent aAA cases due to immune reaction have been described. 58 Treatment with ATG may resolve the late graft failure in such cases.…”