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

UK MRCIO: EVALUATION OF AUTO-BMT IN ACUTE
MYELOID LEUKAEMIA
A.K. Burnett, A.H. Goldstone, R.F. Stevens, 1. Hann, J. Rees, R. Gray and
K.Wheatley, on behalf of the Adult and Childhood Working Parties.
Plentiful anecdotal data has suggested that autologous BMT will reduce relapse
risk for a substantial proportion of patients with AML. In previous MRC
Trials (AML8 or 9) which ran through most of the decade to 1988, investigators
were given the option to perform autologous BMT in first remission if they
wished. While this non-randomized assessment is not free from sources of bias,
at least prior therapy and time censoring effects were known. Patients who received
auto BMT have a survival of 67% at 5 years compared with 55% for trial
recipients of allografts, and 45% for those who received chemotherapy alone. All
such data persuaded the MRC Working Parties to commence a new trial to better
define the role of auto BMT in patients with AML under 55 years old.
The major questions were: (1)
does transplant (auto or allograft) confer any
additional benefit to patients who have already received intensive chemotherapy?
(2)
Is it as effective to collect marrow in first remission but reserve the
autograft for those who relapse and enter second remission? The protocol design
is shown in figure 1. All patients who fulfill the criteria for AML - including
those who may have had an antecedent hematological disorder - are randomized
to receive either DAT (3 + 10) and (3 + 8) or ADE (10 + 3 + 5) and (8 + 3 + 5)
as the first two courses. Remission status is checked after each course. When CR
is not achieved after the second course, participants are free to remove the patient
from protocol for alternative therapy. All patients will then receive a further
2 courses (MACE and MidAC) of intensive treatment. During this time the
availability of a sibling donor will be established. Those patients for whom allograft
is not available have bone marrow harvested immediately before the
MidAC course, and are randomized to have Auto BMT using cyclo+TBI with
unpurged marrow or to STOP treatment. Those randomized to STOP would
receive an autograft if they relapse, and enter a second remission. Patients who
relapse within 6 months of the harvest are recommended not to receive an
autograft using that marrow because the risk of occult contamination is considered
high. The second remission autograft will use Busulphan/Cyclophosphamide
myeloablation because the data available at the time using TBI in CR2 was
not encouraging. It was recognized that the four chemotherapy courses were of
an induction level of intensity and that this may prevent some patients progressing
through to BMT, and that the toxicity of BMT might be greater than anticipated.
On the other hand it was regarded as important to minimize the early
relapse risk (censoring effect) and ensure that the best possible chemotherapy
was available for comparison.
SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 1