autologous blood and marrow transplantation - Blog Science ...

344 Chapter 6: Breast Cancer
after 1992, these patients were no longer treated on high-dose protocols.
The source of stem cells included autologous bone marrow, peripheral blood, or
a combination of both. Patients undergoing autologous bone marrow harvesting
were required to have no evidence of bone marrow metastases after histologic and
immunohistochemical analysis of the bone marrow before harvesting. Bone
marrow were also evaluated retrospectively for the presence of micrometastases
using a polymerase chain reaction (PCR) method to detect the presence of
cytokeratin 19 (K19). 8
Peripheral blood stem cells were harvested after a variety of
mobilization techniques using hematopoietic growth factors, alone or in
combination with chemotherapy. These regimens have been discussed
elsewhere. 9
' 10
High-dose chemotherapy regimens have been described elsewhere 11
and
included ifosfamide, carboplatin, and etoposide (ICE), thiotepa and mitoxantrone
(MITT), thiotepa, mitoxantrone, and paclitaxel (TNT), topotecan, ifosfamide, and
etoposide (TIME), busulfan and cyclophosphamide and busulfan (BUCY), and
cyclophosphamide, thiotepa, and carboplatin (CTC). Evaluations of ICE, MITT,
TNT, and TIME were conducted as part of phase I/II dose-escalation trials.
Evaluations of BUCY and CTC were conducted as part of phase II trials. Table 1
describes the maximum tolerated doses for each chemotherapy regimen used in
these trials.
• Patients were followed with routine physical examinations, radiographic
examinations, and laboratory studies for evidence of disease progression at 3, 6,
and 12 months after the completion of high-dose therapy and yearly thereafter for
a minimum of 5 years. Evaluation of progression-free survival was performed for
all patients who were a minimum of 6 months posttransplant and was calculated
using the Kaplan-Meier method. Differences in survival were evaluated using the
log-rank method.
RESULTS
We treated a total of 442 patients from October 1989 through December 1997.
Patient characteristics are shown in Table 2. All patients were female. As
previously noted, the minimum follow-up at the time of this analysis was 6 months.
Figure 1 illustrates progression-free survival for all patients with stage II and
stage III disease based on number of lymph nodes in patients with stage II disease
or, in patients with stage III breast cancer, the presence or absence of inflammatory
breast cancer. There was no difference in progression-free survival based on the
high-dose regimen employed (P=0.96), estrogen receptor status (P-0.2S), or age
(55 years) (P=0A). Factors that adversely affected progression-free
survival included the presence of minimal bone marrow metastases as detected by
reverse transcription (RT)-PCR for K19 (P=0.059) and the use of peripheral blood