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

Role of Marrow Purging
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the leukemia-free survival (LFS) was higher, and the probability of relapse was
lower in recipients of purged than of unpurged marrow (63 % versus 34%, p =
.05 and 23% versus 55%, relative risk 0.34, p = .005, respectively). The
superior results of purging were most obvious in patients autografted within 6
months of achieving CR (probability of relapse, 20% versus 61%, p = .01).
Patients with longer intervals between CR and autografting had higher LFS and
lower probability of relapse than those autografted early in CR (intervals greater
than 9 months, 7 to 9 months, 4 to 7 months, and < 3 months : LFS = 56%,
40%, 35%, 27%, p = .007, probability of relapse = 25%, 56%, 59%, 67%,
p = .005; respectively). We concluded that marrow purging with mafosfamide
was valuable for patients autografted early in first CR.
b) The 1990 survey confirmed the efficacy of marrow purging in AML
CR1, not only after TBI, but even when considering me whole population of
patients autografted in CR1 whatever the pretransplant regimen. It further
extended the observation mat die efficacy of marrow purging was easier to
detect in patients more likely to have persisting residual tumor at time of
ABMT, with the finding of a statistically significant advantage for purging in
patients achieving CR1 with a delay from initial to CR1 > 40 days, and not in
those with a delay < 40 days. For the 1990 EBMT survey, 62 European teams
(see appendix) reported 1688 autografts for consolidation of acute leukemia, as
of December 31, 1989. The distribution for bone marrow transplant (ABMT)
was the following: AML: status CR1:671; CR2:196 - pretransplant regimens
: total body irradiation (TBI): 456, Busulfan + Cyclophosphamide (BU-CY)
174. Marrow purging with mafosfamide 269 corresponding to 26% of the
patients in CR1 and 41% in CR2. ALL status : CR1 312, CR2 259
pretransplant regimens : TBI 537, BU-CY 52. Marrow purging with
mafosfamide 256, with monoclonal antibodies 175 corresponding to 61%
purged in CR1 and 75% purged in CR2. The overall results were die following
: for patients autografted in CR1, the leukemia free survival and relapse rates
at 7 years were 48 ± 2% and 41 ±3% for AML (fig 1) and 44+_ 5% and 45
± 5% in ALL (fig 2). In CR2 the figures were LFS 34 +/- 4% and relapse
rate 54 ± 5% for AML and 32 ± 3% and 62 ± 4% respectively for ALL.
Patients not relapsing at 1 year post ABMT had a probability of being cured at
7 years of 86% and 71% if autografted in CR1 and CR2 for AML (fig 3), and
81 % and 59% for ALL (fig 4). Multivariate analysis of relapse rates in several
subpopulations confirmed the efficacy of marrow purging in AML CR1: in
patients transplanted prior to January, 1988 (minimum follow up 2 years), the
relapse rate with purged marrow was 35 ± 5% vs 47 ± 3% (p = 0.005) (fig
5). In patients autografted after TBI only, it was 29 ± 5% vs 50 ± 4% (p <
0.0001) and further 16 ± 6% vs 60 (p = 0.001) in those autografted within 6
months from induction of CR (fig 6). In patients autografted after TBI who
reached CR1 with a delay from diagnosis to CR1 > 40 days, the figures were
23 ± 8% vs 56 ± 6% (p = 0.001) in favor of purging while relapse rates with
and without purging were similar in those who initially reached CR1 within 40
days. Results were also significant in multivariate analysis though at lower
levels when considering all patients autografted until December, 1989. Finally,