Autologous Bone Marrow Transplantation - Blog Science Connections

ABMTin 65 Patients With Neuroblastoma 415
As is shown in Figure 2, the probability of nonprogression at 20 months
postgraft is not better for patients grafted in CR or VGPR (37% versus 34%). At
this time, with a median follow-up of 18 months postdiagnosis, results for the
PR group are better than those of our early reports (19). But this is an interim
analysis with a rather large interval of confidence, and more follow-up is
needed for this particular conclusion. The difference between the two groups
(CR-VGPR and PR) has not been significant since the study began. In the
current study, a clear improvement is shown at 2 years postgraft (24%
progression-free survival compared with 1 % for the historical control), but no
conclusions can be reached at this time regarding long-term survival. Patients
in CR or VGPR at the time of BMT would obviously be a group for whom
long-term survival might be expected. The ENSG study will provide an
answer to how effective high-dose melphalan alone is as late consolidation in
patients in CR or "good PR," and it will also show survival data for patients
achieving CR who were not grafted. The inclusion of TBI in many intensive
therapy regimens is a result of the Philadelphia experience, at a time when
alternative high-dose chemotherapy regimens had not been introduced into
pediatric practice (7,8). Recent studies such as those of Hartmann et al. (26)
suggest that it may be possible to achieve comparable results without TBI,
using two courses of intensive chemotherapy for the CR-VGPR group. The
result of this experience is clearly different, however, for the subgroup of 12
patients who are comparable to our PR group (no progression-free survivors
at 12 months for the Hartmann et al. group and 40% progression-free
survivors in this group of 31 PR patients (6, see also Hartmann et al.
"Repeated High-Dose Chemotherapy Followed by Purged Autologous Bone
Marrow Transplantation as Consolidation Therapy in Metastatic Neuroblastoma,
in this volume). The long-term toxicity of two courses of high-dose
alkylating agent is as yet unknown (26,27). The short- and long-term
complications of TBI are clearer from experience in children with leukemia
(2), and its omission, if it were possible, would be welcome. The young age of
many of the patients with neuroblastoma adds to this concern. Nevertheless,
the reduction in pulmonary and possibly CNS toxicity with fractionated TBI,
our preliminary results from the group of PR patients, and the experimental
background that favors this therapeutic modality inclines us toward continuing
this procedure. In the present study, the treatment-related morbidity was
not markedly different from our early experience with intensive therapy for
lymphoma, in which we used a protocol without TBI but in which the
incidence of VOD was of concern (23).
The issue of ex vivo purging is also important. In the present study, the
use of all techniques described was highly experimental in nature—these are
essentially phase I studies. We demonstrated that they do not harm, and graft
take is not inhibited. The occurrence of early marrow relapse, despite
purging, and the even more striking occurrence in one patient of what
seemed to be tumor embolization, might be seen as indicating that purging