Immunologic Research

, Volume 28, Issue 1, pp 13–24

The transplantation of hematopoietic stem cells after non-myeloablative conditioning

A cellular therapeutic approach to hematologic and genetic diseases
  • Michael Maris
  • Rainer Storb
Article

DOI: 10.1385/IR:28:1:13

Cite this article as:
Maris, M. & Storb, R. Immunol Res (2003) 28: 13. doi:10.1385/IR:28:1:13

Abstract

Originally, allogeneic hematopoietic stem cell transplantation (HSCT) was viewed as a form of rescue from the marrow lethal effects of high doses of chemo-radiotherapy used to both eradicate malignancy and to provide sufficient immunosuppression to ensure allogeneic engraftment. Clear evience of a therapeutic graft-versus-tumor (GVT) effect mediated by allogeneic affector cells (T cells) has prompted the exploration of HSCT regimens that rely solely upon host immunosuppression (non-myeloblative) to facilitate allogenic donor engraftment. The engrafted donor effector cells are then used to accomplish the task of eradicating host malignant cells. The non-myeloblative regimen developed in Seattle uses 2 Gy total body irradiation (TBI) before transplant followed by postgrafting cyclosporine (CSP) and mycophenolate mofetil (MMF). This regimen resulted in initial mixed donor-host chimerism in all patients with hematologic malignancies and genetic disorders who received HLA-matched sibling allografts. The 17% incidence of graft rejection was reduced to 3% with the addition of fludarabine, 30 mg/m2/day on d-4,-3, and-2. The non-myeloblative combination of fludarabine/TBI has also been successful at achieving high engraftment rates in recipients of 10 of 10 HLA antigen matched unrelated donor HSCTs in patients with hematologic malignancies. By reducing acute toxicities relative to conventional HSCT, most patients have received their pre- and post-HSCT therapy almost exclusively as outpatients. Acute and chronic GVHD occur after non-myeloablative HSCT, but the incidence and severity appear less compared to conventional HSCT. As in conventional transplants, immune dysregulation from GVHD and its treatment and delayed reconstitution of immune function continue to present risks to patients who have otherwise undergone successful non-myeloablative HSCT. Cellular therapeutic effects have been nobserved after non-myeloblative HSCT such as correction of inherited genetic disorders, and eradication of hematologic malignant diseases and renal cell carcinoma via GVT responses.

Key Words

Hematopoietic stem cells Graft-versus-tumor effect Non-myeloablative transplants 

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Michael Maris
    • 1
  • Rainer Storb
    • 1
  1. 1.Fred Hutchinson Cancer Research Center, Seattle, WAUniversity of WashingtonSeattle

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