autologous blood and marrow transplantation - Blog Science ...

10 Chapter 1: AML
years that a significant survival advantage emerged. In summary, therefore, of six
major trials aimed at evaluating the role of autografting in AML in first remission,
overall survival benefit has been demonstrated in only one trial, where follow-up
was prolonged.
These results do not at first sight suggest that autografting has a routine role in
first remission. There are a number of features of this extensive trial experience that
deserve closer examination. The single-center and registry data suggested that
45-55% of patients who received an autograft would become long-term survivors.
Even on the intent-to-treat analysis, this has been exceeded in most trials. In
virtually all trials, the autograft resulted in a significant reduction in relapse risk
even though not all patients allocated to autograft actually received it. Perhaps the
clearest example of this was in the MRC trial. Here the survival at 7 years from
diagnosis with chemotherapy alone was 40%, which is at least equivalent to that
achieved by high-dose Ara-C schedules. 1
However, the addition of autograft as an
extra treatment course was able, on an intent-to-treat analysis, to reduce the relapse
risk from 58 to 37%, even though one-third of the patients allocated by randomization
to autograft did not receive it. So the substantial antileukemic effect was
provided by only two-thirds of the patients. Arguably if they all had received it, the
relapse risk could have been reduced further. Compliance with allocated treatment
in these trials varied between 54 and 88%. In some cases, this was partially
explained because after randomization patients had to undergo a further course of
chemotherapy before receiving the autograft (as in the MRC trial). In some cases
there was a delay in delivering the autograft, which resulted in some patients
relapsing (as in the US Intergroup Trial).
The beneficial effect on relapse was counteracted by two factors. First, there
were more deaths in the autograft arm. Most, but not all, followed autografting. The
risk of death varied from 3 to 15%, which is higher than that expected (6-8%) from
the single-center reports. In the MRC trial, where 12% of recipients of autograft
died, the reasons were largely associated with poor quality of hematologic
engraftment. If autografting is to fulfill its antileukemic potential, it has to be made
safer. It remains to be seen whether the change to peripheral blood stem cells will
improve the situation.
The second main confounding factor was that in several of the trials, patients
who relapsed from the chemotherapy arm were more successfully rescued by
further treatment. This is well illustrated in the EORTC-GIMEMA trial and to
some extent in the US Intergroup trial. In general, previous experience in the
treatment of AML suggests that once a patient has relapsed, the prognosis is very
poor. On the other hand, registry data persistently demonstrate a durable survival
of about 25-35% in patients who received a transplant in second remission. What
has been unknown to date is how representative patients transplanted in CR2 were
of all patients who relapsed. In other words, what was the denominator against