V Autologous Bone Marrow Transplantation_2.pdf - Blog Science ...

4
Session 1: Acute Myelogenous Leukemia - CR1
(Daunorubicin, Ara-C, Thiogmanine) with "ADE 10+3+5" (Ara-C,
Daunorubicin, and Etoposide) as remission induction treatment.
MATERIALS AND METHODS
Rationale of Trial Design
The rationale of the MRC AML 10 Trial design (figure) has some
specific points. It is intended that all entrants, who must be under 55 years of
age, should have identical chemotherapy pre-transplant comprising four courses.
The evaluation of transplantation (allogeneic or autologous) will be based on its
potential additional value compared with no further chemotherapy. The
induction and consolidation phases of chemotherapy are designed to achieve a
high rate of remission, and subsequently be of adequate intensity (a) to achieve
the maximum leukaemic cytoreduction as a means of "in vivo purging" of the
harvested marrow, (b) to minimize the risk of relapse during the period of
pre-transplant remission and (c) to provide as good a prospect as possible of
curing patients without recourse to BMT which will be seen in the STOP arm.
On the other hand it was hoped that the chemotherapy would not be sufficiently
severe to prevent patients' progression through the protocol, or to damage the
regenerative potential of the graft or increase the toxicity of a subsequent
transplant.
The myeloablative protocol will be cyclophosphamide/TBI in first
remission but will be Busulphan/Cyclophosphamide in second remission because
uncontrolled data suggest that it may be superior to TBI in this context (8).
PROGRESS REPORT
The study opened in summer 1988. At June 1990, 494 patients were
on study, including 109 children. Of 373 évaluable, 299 (80%) have entered
remission (226/292 adults 77%; 73/81 children 90%). Of those who remitted,
71% achieved CR after course 1, and 24% after course 2, so about three
quarters of the patients will receive 3 courses of post-remission induction
therapy. Important haematological toxicity occurred after courses 3 and 4. The
median times taken to regenerate neutrophils to 1.0 x 10*/1, were 17, 18, 24
and 31 days after the four courses, respectively. Similar prolongation of
thrombocytopenia was noted. Regeneration of platelets to SO X 1071 being
achieved respectively in 16, 19, 24 and 25 days.
Ten patients have relapsed during the time scale of the post-induction
chemotherapy, which is an actuarial relapse of 7-8% in the pre-transplant
interval, indicating that few patients are being lost to the transplant option,
which was the main criticism of the autograft data. Ten patients have died in
remission following course 3 or 4. Although this is not an unacceptable rate
(10 out of 360 courses administered 3%), it is, in part, a reflection of the
haematological toxicity of the protocol combined with the traditional approach
of attempting to give post remission therapy on an increasingly outpatient basis.
While the number of days in hospital did not reflect this (27, 22, 25, 25 days