[MOL] Stem Cell Transplants [02000] Medicine On Line


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[MOL] Stem Cell Transplants



Abstract

Background: Despite the initial success of high-dose therapy and bone
marrow transplant, the major reason for posttransplant failure is relapse
of disease. Reinfusion of tumor cells may contribute to relapse in
autologous stem cell transplants. We now have ultra-sensitive methods of
tumor cell detection that can determine the presence of minimal residual
cancer (MRC) in marrow and peripheral blood stem cells. Methods: The author
has conducted a critical review of the literature on this issue.
Results: The factors that are associated with an increase in contamination
of the graft include (1) the number of cycles of induction therapy, (2) the
type of mobilization regimen used, (3) the presence of tumor cells in the
marrow, and (4) the number of phereses. A number of studies show that the
presence of occult breast cancer in the marrow and/or stem cell product
predicts for a poor posttransplant clinical outcome. The presence of
clonogenic breast cancer or lymphoma cells in the graft is also associated
with a very poor outcome. Published data regarding contamination in graft
and outcome for patients with myeloma are limited.
Conclusions: Testing for minimal MRC in the oncology patient provides
prognostic information that may be useful to the transplant physician.
[Cancer Control; JMCC 5(5):406-414, 1998.  1998 Moffitt Cancer Center &
Research Institute]


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Introduction

Autologous bone marrow/stem cell transplant (HSCT) following high-dose
therapy is being used with increasing frequency for patients with breast
cancer, multiple myeloma, and non-Hodgkin's lymphoma. Despite the initial
success of this therapy, the major reason for posttransplant failure is
relapse of disease. A patient may relapse for multiple reasons, such as a
high in vivo tumor burden, the development of drug resistance, the lack of
an tumor immune response by the patient's hematopoietic cells, or
reinfusion of malignant cells that contaminate stem cell products. The
exact contribution of each mechanism toward a relapse is uncertain at this
time. Reinfusion of tumor cells may contribute to relapse in autologous
stem cell transplant patients. Hence, the detection and quantitation of the
minimal residual cancer (MRC) cells both in vivo and in the graft may be
helpful in determining the prognosis of individual patients. We now have
ultra-sensitive methods of tumor cell detection that can determine the
presence of MRC in marrow and peripheral blood stem cells (PBSC). This new
technology allows us to determine the incidence and clinical significance
of MRC in the HSCT patient. The purpose of this manuscript is to provide a
comprehensive clinical review of MRC data currently reported in the
literature. This includes a review of numerous clinical issues regarding
tumor cell contamination of stem cell/marrow grafts. These issues include
(1) the incidence of tumor cell contamination in stem cell products, (2)
the factors that affect the incidence of contamination, (3) the effect of
cytokines on the mobilization of tumor cells, (4) the association of marrow
disease with the risk of relapse after HSCT, (5) the clinical significance
of tumor cells in the graft, and (6) the use of stem-cell isolation
platforms (eg, CD34 selection devices, ex vivo expansion) for purging tumor
cells from the stem cell product.

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