Autologous Bone Marrow Transplantation - Blog Science Connections

532 ABMT in Melanoma
chemotherapy and autologous marrow rescue. Informed consent, approved
at each institution, was obtained before beginning treatment.
Marrow Processing
Before high-dose therapy was administered, marrow was collected and
cryopreserved by standard methods (3). Histology was normal and the
marrow was collected a minimum of 4 weeks after previous chemotherapy. It
was then cryopreserved in dimethyl sulfoxide and kept at -196° C in the liquid
phase of liquid nitrogen. Three to four days after completing chemotherapy,
the marrow was rapidly reinfused intravenously.
Chemotherapy
Dose escalation of the chemotherapy was accomplished by a modified
Fibonacci scheme. During the single-agent studies, the total dose was
administered over 3 days and given intravenously over 2 hours (carmustine,
thio-TEPA) or by rapid intravenous bolus administration (melphalan). When
the combination of carmustine and melphalan was given, the starting dose
was 50% of the maximally tolerated dose determined in the respective phase I
single-agent study. Each drug was escalated singly, holding the other drug
dose constant. The melphalan was administered for the first 3 days followed
by carmustine on the subsequent 3 days.
Evaluation of Response
Responses were defined using standard criteria. Complete response
(CR) was the complete disappearance of all measurable disease for more
than 1 month; partial response (PR) represented a more than 50% reduction
of measurable disease; any response less than partial was considered no
response (NR). Duration of response was calculated from the day of marrow
infusion. The results of our phase 1 and II studies have been previously
reported (4-8) and have been updated. For statistical comparisons, the
confidence interval method described by Simon, Fisher's exact test, or chisquare
method were used (9).
RESULTS
The results of treating advanced melanoma in patients with maximally
tolerated doses of carmustine, melphalan, or thio-TEPA are presented in
Table 1. These doses were determined to be the maximally tolerated doses in
the phase I trials. In the case of thio-TEPA, there was a dose-response relation
noted at 900 mg/m 2 , with a significantly higher response in patients receiving
more than 990 mg/m 2 compared with patients who received 180-720
mg/m 2 . The overall response rates for melphalan and thio-TEPA were better
than for carmustine. The lower response rate for carmustine can be