Blood, 1 June 2001, Vol. 97, No. 11, pp. 3671-3672
CORRESPONDENCE
To the editor:
Intensive chemotherapy versus bone marrow transplantation in
pediatric acute myeloid leukemia: a matter of controversies
Woods et al1 emphasized allogeneic bone
marrow transplantation (BMT) as treatment of choice for children with
acute myeloid leukemia (AML) in first remission. They supported this
recommendation with the results of the randomized Children's Cancer
Group (CCG) 2891 study comparing 3 aggressive treatment regimen in
children with AML in remission. A superior survival after achieving
remission was achieved with matched related allogeneic BMT
(60% ± 9%), compared with chemotherapy alone (53% ± 8%) or
autologous BMT (48% ± 8%). Results were even better in patients
receiving intensive-timing induction treatment.
We disagree with the general recommendation of allogeneic BMT for all
AML patients. From a methodological point of view, this statement
should not be generalized, but it may be right for specific therapy
regimens. Furthermore, in children with favorable cytogenetics [t(15;17), inv(16), or t(8;21)] the indication for
allogeneic BMT in first complete remission (CR) cannot be seen.
Thirty (38%) of the 79 children receiving transplants in the CCG study
belonged to this group,1(Table1) whereas in the
chemotherapy group only 18 (23%) of 77 patients had favorable
cytogenetics (P = .048). But outcome did not differ, compared with the non-BMT group.1(Table4) Regarding
children with AML FAB M3 and t(15;17) who probably will be cured by
less intensive chemotherapy (especially, when treated in combination
with differentiating agents like all-trans-retinoid acid), there is
generally no indication for BMT.2-4
We do agree that intensification of induction treatment has improved
outcome in children with AML.5 Analysis of patient groups
in the Berlin-Frankfurt-Münster study (AML-BFM 93) (n = 471)
comparable with those of the CCG trial (children with AML FAB M0-7,
excluding Fanconi anemia, Down syndrome, secondary AML, and
granulocytic sarcoma, in contrast in AML-BFM 93 only patients younger
than 18 years) showed that the overall 5-year survival rate of
all children, not only those in remission, was 59% ± 2%. This was
considerably higher than of the total patient group of the CCG 2891 trial (CCG estimated 40%; intensive timing 49% ± 5%;
standard timing 34% ± 6%). Events 5 years after diagnosis were
extremely rare in the BFM studies, and therefore, estimates are
comparable. It is surprising that the survival curve from the BMT group
in the CCG study shows no plateau after more than 5 years.1(Fig2) This is in contrast to the chemotherapy
groups in the CCG and in the BFM study.
Regarding children in remission only, as reported in the CCG
paper, the 5-year overall survival in the AML-BFM 93 study (n = 386)
was 71% ± 3% (matched related-BMT 70% ± 8%,
n = 30; chemotherapy alone 71% ± 3%; n = 356). Considering all
children with AML in remission of studies AML-BFM 87 and 93 (between
1987 and June 1998, n = 616), the 5-year overall survival
was 67% ± 2%. In contrast to the CCG study, outcome was
predominantly achieved by intensive chemotherapy alone (chemotherapy,
n = 546; MR-BMT in first remission, n = 44 [7%]; other, n = 26
[ie, 4%]; autologous BMT, n = 11; alternative donor BMT,
n = 15).
Most recently, our data were supported by the results of the Medical
Research Council (MRC) 10 and 12 trials, failing to show a benefit for
allogeneic BMT.6,7 Intensive chemotherapy regimens such as
AML-BFM 93 or MRC 10/12 including intensive induction, consolidation,
and high-dose postremission treatment and sufficient supportive care
seem to achieve therapy results similar to allogeneic BMT, with less
severe late effects.8-10 And although several other pediatric studies reported superior results of allogeneic
BMT,11-14 results for the total groups were inferior.
Therefore, a benefit of allogeneic BMT may be achieved for patients
treated with less intensive induction and consolidation treatment.
As a consequence, one could argue that allogeneic BMT should always be
considered in context with the applied protocol. Due to the favorable
outcome (survival rate higher than 70%) in children with standard
risk AML (standard risk group: AML M1/M2 with Auer rods
or t(8;21), AML M4eo or inv(16), and less than 5% blasts at day 15;
AML FAB M3 with t(15;17) regardless of their blast count on day
15),15 these patients were excluded from matched related-BMT in first CR in study AML-BFM 93. This had the advantage that the potential morbidity of the transplantation procedures can be
avoided in the majority of these patients. Patients with standard-risk
AML will either not suffer from relapse at all or suffer predominantly
from late relapse. According to our data, the probability to achieve a
second remission is high in late relapses allowing BMT in second
CR.16 Whether there is a benefit by BMT in first CR for
high-risk patients treated with BFM protocols is the subject of our
current study.
Ursula Creutzig, Dirk Reinhardt, Martin Zimmermann, Thomas Klingebiel, and Helmut Gadner
Correspondence: Ursula Creutzig, Klinik und Poliklinik fur
Kinderheilkunde, Albert-Schweitzer-Str. 33, D-48129 Munster, Germany
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