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Advancements
in Clinical and Basic Science Research from the University
of Michigan Comprehensive Cancer Center
Contents:
From the Editor
The Separation of Graft-Versus Leukemia and Graft-Versus-Host Disease Through
Cytokine "Shields"
Low-Intensity Preparative Regimen and Allogeneic Peripheral Blood Stem Cell Transplantation
Stem Cell Transplantation for Multiple Myeloma
New Approaches for Neuroblastoma
Of Interest
Editor
Laurence H. Baker, D.O.
Deputy Director and
Director for Clinical Research
U-M Comprehensive Cancer Center
Assistant Editor
Maria McKinney White
Director
Marketing and Public Relations
Home Page:
http://www.med.umich.edu/cancer
Michigan Oncology Journal
Copyright ©1999
University of Michigan
Comprehensive Cancer Center
From the Editor
This issue of the Michigan Oncology Journal introduces Jamie
Ferrara. Jamie joined our faculty last fall after an intensive
(and I would add highly successful) search for the directorship
of our Blood and Marrow Transplantation Program. Sam Silver,
who had initially organized our transplant group, became the
director of the Cancer Center's outreach program. Jamie brings
to Michigan a highly successful investigative program on the
pathophysiology of graft vs. host disease (GVHD). He is also
a trained pediatrician, and that fact allowed us to combine
the medical and pediatric transplant efforts into a single
program under his direction.
The first article, "The Separation of Graft vs. Leukemia
and Graft vs. Host Disease through Cytokine Shields,"
describes the latest understanding of the underlying pathophysiology
of GVHD. It lays the groundwork for why biologic response
modifiers such as keratinocyte growth factor and interleukin-11,
which have direct protective effects on the GI tract, offer
an attractive new approach to GVHD and its prophylaxis. Much
of the background investigation for this approach was done
by Dr. Ferrara and his colleagues at Children's Hospital in
Boston and the Dana Farber Cancer Center.
Dr. Voravit Ratanatharathorn describes the latest new clinical
approach to the limitations associated with allogeneic stem
cell transplantation. The primary limitations are regimen-related
toxicity and graft vs. host disease. It has been shown that
both complications can be reduced by decreasing the intensity
of the preparative regimen, but the preparative regimen is
still sufficiently immunosuppressive to allow engraftment
of allogeneic hematopoiesis. A "mini-allo" approach
to myelodysplastic syndrome for patients older than 55 years
is described in some detail. A standard allogeneic transplant
could not be done in this older age group. Indeed, Voravit's
initial results are impressive.
Chris Reynolds and Joe Uberti describe the role stem cell
transplant plays in patients with multiple myeloma. Their
article describes the success (or lack thereof) of standard
chemotherapy. There still is not a standard therapy superior
to melphalan and prednisone. The article then describes the
current data supporting high dose chemotherapy with autologous
stem cell support, as well as the data supporting an allogeneic
approach. Our results using allogeneic BMT from sibling donors
in multiple myeloma (60% long-term, disease-free survival)
lead the country. In the future, this group plans to use the
"mini-allo" approach described by Voravit.
Ray Hutchinson reviews several new approaches for metastatic
neuroblastoma including: stem cell transplants; system radiotherapy
with a tumor-targeted agent, MIGB; and a dendritic cell vaccine
approach. The optimism of our pediatricians is clear. Every
success in treating adult cancer patients has followed the
success of treating children.
Laurence H. Baker, D.O.
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