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ch
5
Immune rejection: the
immune biology of allogeneic
hematopoietic stem cell
transplantation (from mice
to humans)
Paul J Martin
Division of Clinical Research, Fred Hutchinson Cancer Research Center and University of
Washington School of Medicine, Seattle, Washington, USA
Robert B Levy
University of Miami School of Medicine, Miami, Florida, USA
83
Introduction
Among the immunological complications of hematopoietic cell transplan-
tation (HCT), graft rejection occurs much less frequently than graft-versus-
host disease (GVHD). Graft rejection must be distinguished from other
causes of graft failure. Failure of initial engraftment (primary graft failure)
can be caused not only by rejection but also by unappreciated abnormali-
ties or insufficient numbers of stem cells in the graft, abnormalities in the
recipient marrow microenvironment, drug toxicity or viral infection. Graft
failure occurring after initial engraftment (secondary graft failure) can also
have multiple causes. For example, drug toxicity can produce marrow dam-
age as direct, idiosyncratic or possibly allergic effects. Viral infections can
depress hematopoietic function either by direct or indirect effects. Aplastic
anemia can occur after infection with hepatitis B virus, and CMV infection
after marrow transplantation sometimes has a myelosuppressive effect.
The morphological changes that accompany graft failure are non-specific.
The problem usually comes to attention because of decreasing leukocyte
counts initially involving isolated neutropenia, thrombocytopenia or retic-
ulocytopenia, or simultaneously involving all three lineages. Occasionally,
a marked atypical lymphocytosis or marrow plasmacytosis may herald the
onset of graft failure. Examination of the marrow usually shows generalized
or patchy hypocellularity sometimes accompanied by non-specific changes
suggestive of damage, such as fat necrosis, granulomas, congestion,
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