Donor leukocyte infusion for treatment of graft rejection post partially mismatched related donor bone marrow transplant

Abstract

Summary:Graft rejection following bone marrow transplantation is more common in patients who receive their grafts from alternative donors and whose marrow is T cell depleted. Rejection in these patients is mediated by persistent host cells that interfere with successful establishment of donor-derived hematopoietic recovery. We describe a patient with chronic myelogenous leukemia in accelerated phase who rejected a T cell-depleted bone marrow graft, 2 months following partially mismatched related donor bone marrow transplant. Unmanipulated peripheral blood donor leukocyte infusion, without additional chemotherapy or immunosuppressive therapy resulted in complete hematopoietic recovery. Cytogenetics and RFLP demonstrated hematopoietic donor chimerism. The patient did not develop graft-versushost disease. Keywords: bone marrow transplantation; graft rejection; donor leukocyte infusion; partially mismatched related donor; CML Graft rejection following BMT remains a significant problem associated with the use of an alternative donor 1 T cell depletion 2 and the diagnosis of CML. 3 Patients who experience immune-mediated graft rejection have evidence of persistent host cells 4 that interfere with engraftment of the HLA disparate hematopoietic graft. Engraftment of additional donor cells requires ablation of allosensitized host cells. However, treatment to eradicate host cells predisposes the patient to life-threatening infection and additional organ dysfunction. To avoid these complications, we treated graft rejection with donor leukocyte infusion (DLI) alone, and in this report we demonstrate that longterm hematopoietic recovery was established.

Clinical and immunologic outcomes following haplocompatible donor lymphocyte infusions

“…A relative paucity of data exists in the literature regarding experience administering haplocompatible DLI, and the informative reports are summarized in Table 3. 1,[6][7][8][9][10] In addition to those listed in Table 3, several other reports exist. Kawano et al 20 describe administration of an unknown dose of prophylactic G-CSF-mobilized haplocompatible DLI to four pediatric patients, all of whom developed Grade I to Grade IV GVHD and ultimately expired from relapse or infection.…”

“…5 The optimal safe dose of DLI that can be administered in the haplocompatible setting is less clear, as only a few reports with small numbers of patients exist on the administration of haplocompatible DLI. 1,[6][7][8][9][10] The source of the T cells utilized for haplocompatible DLI may be important in terms of eventual outcome because of the toleragenic influence of G-CSF on T-cell function. 11 In some reports it is clear that the DLI originated from the cryopreserved CD34À fraction following processing of G-CSF-mobilized PBSC, 9 whereas in other reports the DLI appears to have been obtained from nonmobilized blood collected from the donor after HSCT, [6][7][8] or is not specified.…”

“…1,[6][7][8][9][10] The source of the T cells utilized for haplocompatible DLI may be important in terms of eventual outcome because of the toleragenic influence of G-CSF on T-cell function. 11 In some reports it is clear that the DLI originated from the cryopreserved CD34À fraction following processing of G-CSF-mobilized PBSC, 9 whereas in other reports the DLI appears to have been obtained from nonmobilized blood collected from the donor after HSCT, [6][7][8] or is not specified. 1,10 To determine the safety of haplocompatible DLI, we retrospectively analyzed the clinical and immunologic outcomes of 16 pediatric patients who received G-CSF-mobilized haplocompatible DLI at our two centers.…”

Donor Lymphocyte Infusions for Patients who Relapse After Allogeneic Stem Cell Transplantation for Chronic Myeloid Leukaemia

“…The GVH effect exerted by donor lymphocytes can also be exploited to enhance defective engraftment [45], by displacing residual host haemopoiesis, and to facilitate the reconstitution of the immune system after transplant. In patients who become PCR negative following DLI, two patterns of response have been observed.…”

A prompt graft-versus-thalassemia effect upon withdrawal of cyclosporine A in a child who received allogeneic peripheral blood stem cell transplantation

“…Donor lymphocyte infusion has been used for dissolution of unstable mixed chimerism in recipients of many malignant and nonmalignant hematopoietic diseases after BMT. [2][3][4][5] However, this effect of DLI has rarely been successful in thalassemia major. Aker et al 2 reported that a patient with thalassemia and unstable mixed chimerism after BMT was successfully treated with DLI to attain complete donor-derived reconstitution of the residual hematopoietic host cells.…”