Autologous Bone Marrow Transplantation - Blog Science Connections

546 Carmustine and ABMTfor Malignant Glioma
Adjuvant therapy group
Progressive disease group
—I 1 r — — I — — i 1 I I I I I I I I
6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 106
Survival Time in Months
Figure 1. Survival of patients in adjuvant therapy and progressive disease groups. Open
circles indicate living, progression-free patients; closed circles indicate living patients with
evidence of progression.
DISCUSSION
The responses noted with high-dose carmustine and AJ3MT, particularly
among the long survivors, are unexpected with conventional therapy. Moreover,
although these results are modest, they are similar to those obtained in early
studies using allogeneic bone marrow transplantation for patients with
refractory hematologic malignancy (9). Nevertheless, our results are disappointing
in two ways. First, even patients treated before progression had a high
progression rate; second, toxicity was excessive.
Concerning future studies, several approaches are possible. Patients may
be treated even earlier than those in our adjuvant therapy study, perhaps in a
"neoadjuvant" condition. Also, it is probably naive to expect single-agent
therapy, regardless of dose, to reliably cure clinically apparent malignancy (10),
and the addition of other agents known to penetrate the central nervous system
(e.g., AZQ [aziridinylbenzoquinone], thio-TEPA, VP-16-213) is indicated.
Efforts to decrease the toxicity of high-dose carmustine with ABMT are
essential. Since it is difficult to avoid the conclusion that the dose rates of
carmustine must be reduced to be lower than those we used, it is likely that
earlier therapy with carmustine plus other agents will be required to improve
results.