autologous blood and marrow transplantation - Blog Science ...

Who Benefits From Autograft
in AML in First Remission?
A.K. Burnett
University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Since younger patients with acute myeloid leukemia (AML) can reliably be
induced to enter disease remission 1
" 3
the current priority is to prevent relapse of
disease. Autologous bone marrow transplantation (autoBMT) has been extensively
used in first and second remission and offers long-term survival of 45-55% and
25-39%, respectively. 4
Much of this experience has been derived from single-center
or registry data. A number of prospective clinical trials have now prospectively
evaluated this approach using cyclophosphamide with either total body irradiation
or busulfan as myeloablation and bone marrow as the source of stem cells.
The two pediatric trials reported so far, conducted by the Pediatric Oncology
Group 5
and the Italian AIEOP group, 6
randomized 304 patients. No improvement
in disease-free or overall survival was noted between patients randomized to
receive autograft or further intensive chemotherapy. Of the three trials of this
design in adults, the results have been conflicting.
The EORTC-GIMEMA trial 2
showed a superior relapse-free interval and
disease-free survival in the autograft arm compared with further chemotherapy.
This was explained by the suboptimal effect of the chemotherapy arm but did not
result in an improved overall survival because some patients who relapsed after
chemotherapy were salvaged. The GOELAM study 7
had high-dose cytosine
arabinoside (Ara-C) as the comparison arm and could not demonstrate a benefit for
autograft in either disease-free or overall survival. The recently reported trial
conducted by the US Intergroup, 8
which was very similar in design to the
GOELAM protocol, similarly could not show any advantage in disease-free or
overall survival for the autograft arm.
Two further trials conducted by the Medical Research Council (MRC) in the
U.K. 9
and the Dutch HOVON group had a different design. In these trials,
transplantation was being evaluated as an additional modality in consolidation.
That is, the randomization was to receive or not an autograft (or allograft) after
intensive chemotherapy. The HOVON trial is not yet reported, but the large MRC
trial was able to demonstrate a significant improvement in disease-free survival in
favor of adding an autograft. However, it was only in patients followed beyond 2
9