VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

Higher dose carboplatin with marrow rescue has been even more effective
and the thrombocytopenia seen with lower doses is eliminated by the re-infusion
of cryopreserved hematopoietic stem cells. Shea et al have shown that
carboplatin can be escalated to 2000 mg/m 2
with marrow rescue. He described
in this single agent study, a response rate in patients with refractory ovarian carcinoma
of 55% 7
.
Alkylating agents including melphalan, cyclophosphamide and thio-TEPA
are active in ovarian carcinoma and these agents have also been successfully
dose escalated with marrow rescue 8
- 9
. Stoppa reported a 75% response rate for
patients treated with high dose melphalan who had failed cisplatin induction
therapy. In this study 15/35 patients were alive and disease-free at a median follow-up
of 23 months 10
. Along the same lines Dauplat found a 36% 2 year disease-free
survival for similarly treated patients failing standard induction
therapy 18
. This compares to a median survival of 6-9 months for other salvage
therapies available to patients and a 2 year survival of less than 15%. Based on in
vitro studies demonstrating synergism between cisplatin and either cyclophosphamide
or thio-TEPA in ovarian carcinoma, investigators at Duke University
performed and completed a pilot study of high dose cisplatin, cyclophosphamide
and thio-TEPA with bone marrow rescue in ovarian carcinoma. Of the first
9 patients who had failed at least 2 prior regimens, there was a 78% response
rate, documented surgically even though all had progressed after receiving
cisplatin 12
.
Similarly, mitoxantrone has been shown by Alberts et al to be the most effective
anti-tumor agent at high doses against resistant ovarian carcinoma from
patients in vitro 13
. Because of this and the fact that the drug is nearly devoid of
non-hematopoietic toxicity at conventional doses, several groups have completed
studies of high dose mitoxantrone in patients with refractory ovarian
carcinoma 1415
. Mulder combined either cyclophosphamide or melphalan with
high dose mitoxantrone. Of their initial 6 patients there was a 66% complete remission
rate of up to and beyond 36 months post-therapy. A trial conducted at
Loyola University treated 25 patients with primarily breast and ovarian carcinoma
and demonstrated an overall response rate for ovarian carcinoma of 83%
with 80% of the responses complete remissions 16
. The complete remissions have
lasted up to, and in fact longer than, 30 months, with the median survival for
this heavily pre-treated group of 12 months.
SURVEY RESULTS
Based on enhanced responses to high dose chemotherapy with ABMT,
many U.S. groups are now performing transplants for advanced ovarian carcinoma.
Because of the small numbers treated to date at each center, very little has
been published. Yet as in the pilot studies as above, it is the feeling of many investigators
that this form of therapy is effective in treating end stage disease, and
that this therapy should be used earlier in the course of the disease to improve
results, as has been done for patients with leukemia and lymphoma. To provide
additional support for this therapy in this country, a survey of the U.S. programs
known to be active was conducted in November, 1992. The survey was designed
to determine the number of patients treated, the regimens used, the remission
status, several prognostic factors, as well as response rates and durations (Table
SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 193