autologous blood and marrow transplantation - Blog Science ...

286 Chapter 6: Breast Cancer
In 24 other patients, major changes in histology were found, such as tumor cell
necrosis and stromal alteration showing partial efficacy of chemotherapy (grade
III). However, an invasive component was persistent in these patients.
Finally, in 34 patients, despite good clinical response, no evidence of pathologic
response to chemotherapy (grade IV) was seen.
Objective evaluation of response rate in breast and lymph nodes was difficult to
assess since several patients had pathologic CR in the breast but had undergone
previous axillary dissection. However, dissociation of response was clearly
observed in some other patients, since eight patients had positive lymph node
dissection despite pathologic complete response in the breast.
At present, with a follow up ranging from 12 to 34 months after inclusion, 31
patients have relapsed (local relapse or metastasis) and 14 have died.
DISCUSSION
Acute toxicity related to chemotherapy mainly consisted of severe but
reversible pancytopenia in all four cycles of chemotherapy. The second cycle of
chemotherapy was less toxic, leading to fewer cases of severe neutropenia, febrile
neutropenia, thrombocytopenia, and platelet transfusion. This difference was
expected, since cycle 2 differed from cycle 1 in the cyclophosphamide dose (3 g/m 2
vs. 6 g/m 2
) and from cycles 3 and 4 by the absence of 5FU.
The relatively short duration of neutropenia is probably related to use of rG-CSF.
One can question the utility of peripheral blood stem cells in this study, in which
there was no myeloablative chemotherapy. However, the incidence of severe
neutropenia, thrombocytopenia, and febrile neutropenia did not increase from cycle
1 to cycle 4. In previously published studies of high-dose doxorubicin-cyclophosphamide
regimens with rG-CSF but without stem cell transplantation, 17-19
thrombocytopenia
is generally the dose-limiting toxicity and appears to be cumulative,
increasing significantly between the first and last cycles. 17
Overall, peripheral blood
stem cells appear to permit a safer and more regular increase of dose intensity in
high-dose sequential chemotherapy regimens, as previously described. 20
' 21
One of the risks in using peripheral blood stem cells is the mobilization,
collection, and reinfusion of tumor cells. 22
This is a potential risk in our study in
which most patients had the blood stem cell collection after the first cycle of
chemotherapy. However, the significance of circulating tumor cells and their
impact after reinfusion are not yet clearly established. Moreover, ex vivo therapy
is not considered standard practice at present.
Nonhematologic toxicities were almost entirely mucositis, occurring more
frequently after cycle 3 and 4 and probably related to administration of 5FU.
Relative dose intensity was 0.97 (range 0.4-1.04) for cyclophosphamide and
0.96 (range 0.25-1.05) for doxorubicin. Eighty-seven patients received four cycles