Allograft and Autograft Purging Using Immunotoxins in Clinical Bone Marrow Transplantation for Hematologic Malignancies

Abstract

Bone marrow manipulation is an essential procedure when bone marrow transplantation (BMT) is used to improve the chances of survival among high risk patients with hematologic malignancies. Ex vivo purging of donor T cells effectively prevents a fatal reaction known as graft-versus-host disease in allogeneic BMT. Ex vivo purging of residual leukemia cells from autologous marrow can virtually eliminate the risk of autograft contamination. Immunotoxins are powerful and selective reagents for these tasks. However, ex vivo purging may be insufficient by itself to overcome the high risk of relapse that confronts many patients undergoing autologous BMT. Bone marrow manipulation may even present problems of its own, such as loss of the graft-versus-leukemia effect when allogeneic marrow is T cell depleted. We are currently evaluating immunotoxins containing pokeweed antiviral protein in clinical trials as in vivo purging reagents that may reduce the risk of relapse for BMT patients.

Autologous stem cell transplant in ALL: who should we be transplanting in first remission?

“…Although ex vivo purging can decrease the number of leukemic progenitor cells in the autologous graft, there is no correlation between purging efficacy or the dose of residual tumor infused and the outcome. [22][23][24] …”

Autologous Stem Cell Transplantation in Acute Lymphocytic Leukemia

“…In the context of ASCT, detection and quantification of MRD have been done in the past decade by the Minneapolis team on 14 patients with high‐risk T‐cell acute lymphoblastic leukemia (T‐ALL) autografted with marrow purged by immunotoxins and 4 hydroperoxycyclophosphamide (4HC) [7], 14 patients with high‐risk B‐cell acute lymphoblastic leukemia (B‐ALL) autografted with marrow purged by monoclonal antibodies (mAbs) and 4HC [8] and later, extended to a total of 83 adult ALL patients [9]. Leukemic progenitor cells were quantified after cell sorting with specific mAbs and culture.…”