autologous blood and marrow transplantation - Blog Science ...

408 Chapter 7: Solid Tumors
relapse in certain hematologic malignancies and neuroblastoma. 84-86
Similar
experiments in solid tumors have not yet demonstrated gene-marked tumor cells in
relapse sites. 87
It remains that these cells may also serve as a marker to indicate the
patient has increased systemic chemotherapy-resistant tumor burden.
In SCLC, the marrow is one of the most common metastatic sites. By immunohistochemical
techniques (sensitivity of 1 in 10 4
cells), subclinical micrometastatic
disease is detected in marrow in 13-54% of newly diagnosed limited-stage and
44-77% of newly diagnosed extensive-stage SCLC patients. 88-92
Of patients in
complete response, two tiny series suggest two-thirds have subclinical disease in
marrow. 93,94
In one paper, residual tumor appeared to predict relapse. 94
Brugger
and colleagues have reported circulating tumor cells in patients with metastatic
9 5
SCLC or breast cancer mobilized with G-CSF and IPE chemotherapy Circulating
tumor cells were not observed after the second cycle of chemotherapy, supporting
the contention that in the short term, in vivo chemotherapy induction may "purge"
the patient and the autologous stem cell source. 65
In our unpublished data, up to
77% of limited disease patients in or near complete response before high-dose
therapy have detectable tumor cells in their marrow by keratin staining.
Although many chemotherapeutic agents have major clinical activity against
overt SCLC, the uniform clinical outcomes suggest that these different systemic
drugs fail to eradicate a coincident population of tumor cells, presumably enriched
for in vivo resistance mechanisms. Molecular and antigenic characterization of
these residual cancer cells may guide strategies for further treatment. We are using
a fluorescence microscope with automated computerized scanning with one set of
fluorescent probes for detection and a second set with different fluorophores for
biologic characterization to analyze patterns of coexpression of various markers in
these cells. 96
Prospective trials to determine the clinical significance of marrow or
peripheral blood tumor contamination and the impact of novel stem cell sources to
support high-dose therapy are underway.
CONCLUSION
Two major strategies to administer high-dose therapy for SCLC include doseintensive
multicycle approach as initial treatment and the "later" intensification in
responders. Advantages for each approach are evident. The multicycle approach
can achieve early dose intensity and maintain it for about three to four cycles.
Disadvantages to this approach include subtransplant doses, high mortality rates,
late administration of chest radiotherapy (except for the relatively low-dose
radiotherapy in the recent Humblet trial), and the collection of stem cells early in
treatment when they are more likely to be contaminated with tumor cells.
Advantages to later intensification include a patient with decreased tumor burden
and tumor-related symptoms with consequent improved performance status, a