Biology Reference
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understanding of regulatory cell populations, enhanced MRD analysis,
and a more facile manipulation of effector cells. In total, these efforts have
begun to shift allogeneic transplantation toward a structured manipulation
of interconnected immune responses. Individualized care, with treatment
decisions made in real time based upon both disease and patient-specific
factors, appears to be on the horizon.
A possible “personalized” treatment course of the future could unfold as
follows (
Figure 21.1
). Risk assessment of malignancy will begin at diagno-
sis and continue with analysis of MRD after induction chemotherapy. For
patients with significant MRD, additional consolidative chemotherapy
could optimize pretransplant disease control. The subsequent condition-
ing regimen will be disease-specific (e.g. clofarabine for active AML) and
GVHD prophylaxis will include infusions of regulatory T cells that should
not impede GVL effects. Meanwhile, SAHA therapy could provide both anti-
tumor and anti-GVHD efficacy. Anti-leukemia maintenance therapy will
begin shortly after transplant in patients at highest risk for relapse. Regu-
lar monitoring post-transplant will assess for both relapse status by MRD
and the onset of GVHD through biomarker panels. Both evaluations will
guide levels of immunosuppression and potentially trigger the addition
of disease-specific immunotherapies, such as haploidentical NK cells or
genetically engineered T cells for patients at risk of relapse. If biomarkers
predict a high risk of severe GVHD, the patient will receive additional infu-
sions of regulatory T cells. Biomarker panels will also monitor the response
to GVHD treatment and guide tapering or intensification of therapy. In the
end multiple individualized immunologic interventions will balance the
potential for GVHD with the ongoing risk of relapse, facilitating an acceler-
ated application of personalized medicine to allogeneic transplantation in
the coming decade.
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In conclusion, the annual number of BMTs continues to increase about
6-7% per year on a worldwide basis. That rate is likely to accelerate over
the next decade as allogeneic BMT becomes safer and more effective. As
molecular diagnostics improve, allogeneic BMTs from unrelated donors
are likely to be attractive both to patients with high-risk and to those with
intermediate-risk hematologic malignancies. Indeed, unrelated donor
BMTs are increasing faster than any other type of transplant, and the
number is expected to triple in less than a decade. Targeted therapies such
as tyrosine kinase inhibitors will be employed both before and after trans-
plant, reducing the risk of relapse. Biomarkers indicating a high risk for
acute GVHD and other complications will permit preemptive strategies
for patients at high risk, reducing transplant-related mortality and further
improving long-term survival. Allogeneic BMT will become standard for
patients in their sixties, and the overall survival rates for adult patients
should begin to approach the excellent results currently experienced in
pediatric populations.
References
[1] Fraser CJ, Bhatia S, Ness K, Carter A, Francisco L, Arora M, et al. Impact of chronic graft-
versus-host disease on the health status of hematopoietic cell transplantation survivors:
a report from the Bone Marrow Transplant Survivor Study. Blood 2006;108(8):2867-73.
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