| Applications
 Hematologic
malignancies
Non
hematologic malignancies
Hemoglobinopathies
|
"Allogeneic
bone marrow transplantation (BMT) is an effective treatment for
hematologic malignancies. The curative power of BMT is due to the
cytoreductive effects of the high-dose chemoradiotherapy in the
conditioning regimen and to the adoptive immunotherapy of the donor
graft. For many years, it was thought that the intensive conditioning
regimen was responsible for most of the antineoplastic activity.
However, retrospective analyses of outcomes of allogeneic transplants
for acute myelogenous leukemia (AML) indicated that the risk for
relapse in patients receiving the same conditioning regimen was
significantly increased by the removal of T cells from the allograft.
Moreover, it has been shown that in patients with relapsed leukemia
after allogeneic transplant, infusions of donor lymphocytes (without
chemotherapy) restore remission as documented by molecular markers,
and these remissions persist beyond 5 years.
These clinical observations, in concert with data
from preclinical animal models, suggest that much of the curative
potential of allogeneic BMT is not due to the conditioning regimen but
rather to adoptive immunotherapy. Thus was born the concept of using
nonmyeloablative transplants to capitalize on donor-mediated
immunotherapy, and, it is hoped, reduce treatment-related mortality (TRM)
associated with intensive ablative regimens.
Several nonmyeloablative conditioning regimens have
been studied. Most regimens have employed a combination of potent
immunosuppressive purine analogs (eg, fludarabine) along with either
low-dose total body irradiation (TBI) or intermediate-dose
chemotherapy with or without antithymocyte globulin (ATG).
A number of centers have demonstrated that stable
donor engraftment can occur with nonmyeloablative transplants and that
durable tumor remissions with potential curative effects are
plausible.[1-5] Early results suggest that outcomes from
such "mini-transplants" are comparable with traditional
ablative transplants.[3] While graft rejection and
graft-versus-host disease (GVHD) remain formidable risks, attempts to
optimize this transplant strategy are underway. Nonmyeloablative
transplants offer the potential for reducing treatment-related
morbidity and TRM, which may permit the healthcare provider to
administer much of the transplant therapy in an outpatient setting,
and which may extend the use of allogeneic transplantation to patients
who otherwise would be deemed unsuitable candidates for this
treatment."
(Quoted by John R. Wingard,
MD Writer: Michelle L. Plante, PharmD : Nonmyeloablative
Transplants: Is Less More? 42nd Annual Meeting
of the American Society of Hematology [Hematology-Oncology
Conference Summaries - © 2000 Medscape, Inc.]
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