autologous blood and marrow transplantation - Blog Science ...

Kvalheim et al. 253
DISCUSSION
In this study, we looked for the presence of occult tumor cells in bone marrow
and blood in breast cancer patients treated with adjuvant high-dose therapy. Of 124
patients studied, 29% presented with tumor cells in the bone marrow and 8% in the
blood at the time of diagnosis of the breast cancer. The percentage of positive bone
marrow among our well-defined high-risk breast cancer patients is generally lower
than reported by others (Table 1). The differences observed may be due to the
immunocytochemistry protocols used, raising the need to standardize these
procedures.
In this study, we confirm a previous report on mobilization of tumor cells
occurring simultaneously with the presence of CD34 +
cells into the blood. 18
The
question of the clinical significance of infusing tumor cells in our patients cannot
be adequately answered at present. Among the 67 patients studied, 30 patients were
rescued with autografts enriched with CD34 +
cells. Such a procedure gives an
average of 2.5-log tumor cell depletion, and longer follow-up will show if such
highly purified autografts have any influence on disease-free survival. Among
patients with early relapse, no differences could be observed between patients
given unmanipulated PBPC and enriched CD34 +
cells. This indicates that the
relapses occur due to an inefficient high-dose therapy regimen incapable of
eradicating all tumor cells in the patient. Standard prognostic factors such as tumor
size, receptor status, nuclear grading, and number of lymph nodes above eight do
not appear to influence the outcome of patients with early relapse after high-dose
therapy. Therefore, to further elucidate this problem, we are currently characterizing
the primary tumor and the micrometastases with regard to other prognostic
factors such as, p53 mutations, C-erbB2,neu,Her2 oncogene expression, and
others. 19
" 21
Identification and characterization of micrometastases employing immunocytochemistry
are limited by the number of tumor cells found on each slide.
Unfortunately, in our study, and supported by the findings of others, only an
average of one to five tumor cells per 2X10 6
normal bone marrow cells are
detected by immunocytochemistry. To improve the sensitivity and specificity of
the detection methods, there is a need to analyze a higher number of bone marrow
cells from each patient. Standard immunocytochemical methods are cumbersome
for the analysis of large numbers of cells. Recently, in our hospital, we tested the
efficacy of the anti-CD45" immunobead depletion method in 165 bone marrow
samples and 22 PBPC products. 22
- 23
After CD45 depletion of 2X10 7
cells, the
remaining cells were tested for the presence of cytokeratin-positive cells. We found
that an average fourfold higher number of positive cells was detected by CD45
depletion compared with the standard immunocytochemistry procedure. These data
show that anti-CD45-immunobead depletion before immunocytochemistry permits