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21
Looking toward the future: an
individualized approach to
allogeneic transplantation
Craig A Byersdorfer, James L M Ferrara
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
493
An individualized approach to allogeneic
transplantation
The use of allogeneic transplantation to treat hematologic disorders has
grown enormously since it was successfully pioneered in the late 1960s.
The identification and matching of HLA genes in patients and donors have
improved; better supportive care has decreased nonrelapse mortality; the
sources of donor grafts have expanded; and a growing armamentarium of
immunosuppressive reagents has forestalled or averted graft-versus-host
disease (GVHD). Yet despite the hope that allogeneic transplantation brings
to patients with otherwise intractable diseases, many hurdles remain.
GVHD continues to plague an unacceptably high percentage of our patients
and too often leads to death
[1-3]
. Conversely, efforts to minimize GVHD
can abrogate the beneficial graft-versus-leukemia (GVL) effect and increase
relapse rates. Finally, too few of our laboratory successes have translated
into tangible clinical benefits. Nevertheless, we propose that the future of
allogeneic transplant remains bright and that the next decade will witness
more individualized approaches to GVL and GVHD management through a
nuanced manipulation of the immune system.
In this chapter, we project this future in rather broad strokes. We acknowl-
edge from the outset that no single agent will eliminate GVHD or completely
eradicate relapse. Rather, progress will come through detailed monitoring
of each individual's disease course combined with personalized approaches
to immune modulation (see
Figure 21.1
).
Monitoring will begin before transplantation and continue afterwards with
frequent evaluations of GVHD-specific biomarkers and minimal residual
disease, while novel immunotherapies and preemptive “maintenance”
therapy will be tested for patients at the highest risk of relapse. These
changes, if successful, will further expand the indications for allogeneic
bone marrow transplant (BMT).
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