autologous blood and marrow transplantation - Blog Science ...

Slavin et al. 655
up suggests, as published before, that the use of rIL-2 combined with a-IFN
appears to be justified, although a formal study to compare the use of rIL-2 plus a-
IFN with a-IFN alone is not yet available in humans. Taken together,
immunotherapy with cytokines may represent a partial compensation mimicking
GVL effects in conjunction with autoBMT.
INTRODUCTION
AutoBMT is an acceptable treatment of choice for life-threatening disseminated
malignancies that are chemoradiosensitive. The rate of relapse following autoBMT
is >50% in patients with hematologic malignancies treated in first CR, but higher
for more advanced stages of disease. High rates of relapse are also anticipated in
patients with HD and NHL who have failed conventional front-line modalities or
are refractory to primary treatment. AlloBMT provides a better probability of
unmaintained long-term remission, frequently cure, in both acute as well as chronic
leukemia and lymphoma and suggests the therapeutic efficacy of graft-vs.leukemia/lymphoma
(GVL) or graft-vs.-tumor (GVT) effects, which account for
the advantage of alloBMT over autoBMT. 1
" 4
Since a genetically identical donor is
not available for the majority of patients in need of high-dose chemoradiotherapy,
autoBMT may represent not only the safest but most likely the only available
approach for the majority of patients in need.
To reduce the incidence of relapse, our overall goal was to develop new
approaches for induction of autoimmune-like GVL effects following autoBMT
against minimal residual disease (MRD). The availability of an effective approach
for controlling MRD with biotherapy rather than with more intensive myeloablative
therapy is expected to reduce the life-threatening complications that would
arise from further increases in the intensity of non-tumor-specific cytoreductive
measures such as high-dose chemotherapy and radiation therapy included in an
attempt to eradicate or control MRD. In view of the above, and based on successful
studies in animal models of human ALL/NHL with the BCL1 murine B cell
leukemia/lymphoma in cytokine-mediated immunotherapy (CMI) in murine
leukemia, 5-7
we have introduced the use of CMI following autoBMT for reducing
the rate of relapse. 8-11
Based on these data and our current concepts on the treatment of disseminated
malignancies, it seems reasonable to expect that the ultimate goal in the treatment
of widespread disease will consist of maximal tumor eradication by conventional
cytoreductive protocols, preferably autoBMT, toward accomplishing a state of
MRD. Concomitantly, immunotherapeutic approaches will be used to contain
MRD with the aim of controlling, rather than physically eradicating, the last tumor
cell that may have escaped chemoradiotherapy.