Early Allogeneic Blood Stem Cell Transplantation in High-risk Acute Myeloid Leukemia (AML)
Status:
Completed
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
Summary
Karyotype is a major prognostic risk factor in patients with acute myeloid leukemia (AML)
translating into unfavourable outcome in case of poor-risk cytogenetic aberrations. Several
studies have shown that allogeneic hematopoietic stem cell transplantation (HSCT) after
myeloablative conditioning rather than autologous HSCT or consolidation chemotherapy result
in long-term disease control in this group of patients when achieving a first complete
remission. Nevertheless, the complete remission rate achievable is significantly lower than
in patients with a more favourable risk profile. In fact, only the minority of AML patients
with poor-risk cytogenetics, although having a suitable donor, proceed to HSCT due to
refractory disease or infectious complications during induction chemotherapy (IC). Further,
new data show that the course of therapy can be estimated as early as two weeks after the
initiation of the first course of IC with patients presenting with more than 10 % marrow
blasts doing significantly worse than those with a better clearance of blasts. As a result,
the chance to obtain a durable remission is considerably low and most patients with bad-risk
cytogenetics or failure to achieve blast clearance do not proceed to an allogeneic approach.
Together these data indicate that early treatment intensification is warranted in order to
provide the potential curative benefit of allogeneic HSCT to the majority of high-risk AML
patients.
We have shown that reduced-intensity conditioning (RIC) followed by allogeneic PBSC applied
during aplasia after the first cycle of IC in newly-diagnosed high-risk AML patients is
feasible and can result in a sustained disease control. These data prompted us to further
evaluate in a prospective trial an early "up-front HSCT" in patients with newly-diagnosed
high-risk AML defined by karyotype and insufficient blast clearance after the first cycle of
IC.
The goal was to provide an allogeneic HSCT as early as possible after diagnosis in AML
patients.