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Clinical Applications of Mixed Chimerism
Author(s) -
EXNER BEATE G.,
DOMENICK MICHELE A.,
BERGHEIM MARIANNE,
MUELLER YVONNE M.,
ILDSTAD SUZANNE T.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb08482.x
Subject(s) - computational biology , immunology , medicine , biology
A bstract : Bone marrow transplantation (BMT) Is currently a procedure that Is associated with high morbility and mortality. Thus, The clinical application of this technique is limited to the treatment of life‐threatening hematopoietic malignancies. The morbility and mortality of BMT is mainly related to graft‐versus‐host disease (GVHD), failure of engraftment, and toxicity related to fully myeloablative conditioning. GVHD can be prevented by T‐cell depletion. However, T‐cell depletion increases the risk of failure of engraftment. With the identification of a facilitating cell population that enables engraftment of hematopoietic stem cells across major histocompatibility barriers, the dichotomy between GVHD and failure of engraftment has been resolved. If one could overcome the toxicity of conditioning with the development of partially ablative conditioning strategies, BMT could be used for the treatment of a variety of nonmalignent diseases, as well as in the induction of donor‐specific transplantation tolerance. This review outlines the development and advantages of partially ablative conditioning strategies and illustrates possible applications of the technique. Forty years ago E.D. Thomas discussed the potential of BMT for treating immunodeficiencies and for the induction of transplantation tolerance. 1 BMT can be viewed as a natural form of gene therapy to replace a defective cell or enzyme with a functional and normally regulated one.