ASH News Daily - Monday, December 12, 2011 - (Page A-9)
Monday, December 12, 2011
BMT
Are We Finally Getting Smarter When It Comes
To Stem Cell Transplant?
By Michael roSenzweiG, Md, and
heather landau, Md
D
espite significant advances
in biologic therapies for
hematopoietic malignan-
cies, allogeneic hematopoietic stem
cell transplantation (HSCT) often
remains the only curative modality.
However, not only does HSCT
cause significant toxicity, but it fails
to prevent relapse in 10 to 60 percent
of malignant histologies. The
aims of allogeneic HSCT are twofold:
to reduce the tumor burden
with high doses of chemotherapy
and to induce the immunologic
graft-versus-tumor effect (GVT).
The Education Program session,
“Hematopoietic Stem Cell Transplantation
II: Controversies and
Challenges in HSCT,” highlighted
novel strategies of immune manipulation
to enhance antitumor activity
and dampen anti-host toxicity.
Dr. David Porter, Abramson
Cancer Center, University of Pennsylvania,
began the session by
discussing the role of reduced-intensity
transplantation and donor
leukocyte infusion (DLI) to promote
a GVT effect and prevent or
treat relapsed disease. He discussed
methods of ex vivo costimulation of
T cells, which can overcome in vivo
immunesuppression, as well as the
use of adoptively transferred hyperfunctioning
haploidentical NK
cells that can expand in vivo, overcome
self tolerance, and enhance
remission in refractory leukemia
patients (to be presented by Cooley
et al., abstract 355, today at 10:30
a.m.). He highlighted the success
of T-cell targeting with bispecific
antibodies and updated the results
from the series of refractory CLL
patients treated with lentiviral vector
expressing a chimeric antigen
receptor (CAR) with specificity for
the B-cell antigen CD19, coupled
with CD137 (a costimulatory receptor
in T cells) and CD3-zeta (a signal
transduction component of the
T-cell antigen receptor) signaling
domains. He was excited to share
that “massive” expansion of engineered
cells persisted in vivo for
over 12 months. In addition, two
CRs are evident by detailed MRD
studies, well over 15 months following
infusion.
Dr. Katayoun Rezvani, Hammer-
smith Hospital, Imperial College,
London, continued as the second
speaker to address strategies to enhance
the GVL effect through both
active and passive vaccine based
immunotherapy. While the target
antigen is important, so is optimal
timing and modulation of immunosuppressive
effector cells. The
lymphopenic environment in the
post transplant milieu is ideal in
this regard, but clinical success will
likely require a “hybrid” vaccine
approach. Indeed, results from combining
antitumor vaccination in the
host with donor-derived vaccineprimed
lymphocytes are encouraging.
Also exciting is the use of vaccine-primed
lymphocytes from the
patient which are then re-infused
following high-dose chemotherapy
followed by post-transplant booster
immunizations as a way of directing
tumor-specific immunotherapy
in the autologous setting.
Changing the focus from op-
timizing GVT to minimizing the
complications of HSCT, Dr. Michael
Boeckh, Fred Hutchinson Cancer
Center, highlighted the current status
of optimal CMV prevention, detection,
and treatment. In the trans-
plant setting, preemptive treatment
is typical with ganciclovir or foscarnet
but their respective toxicities
of myelosuppression and nephrotoxicty
are often problematic. Newer
agents with even broader activity
hold promise, and results from early
phase studies using CMX001 and
A1C-246 should be forthcoming.
The Scientific Program session,
“Genomics and Proteomics of
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