Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO)
Status:
Completed
Trial end date:
2014-10-01
Target enrollment:
Participant gender:
Summary
Summary Acute promyelocytic leukemia is defined by a characteristic morphology (AML FAB
M3/M3v), by the specific translocation t(15;17) and its molecular correlates (PML/RARa and
RARa/PML). Thereby it can be separated from all other forms of acute leukemia.
By all-trans retinoic acid in combination with chemotherapy cure rates of 70 to 80% can be
reached. On average, about 10% of patients still die in the early phase of the treatment and
about 20 to 30% relapse. Molecular monitoring of the minimal residual disease (MRD) by
qualitative nested RT-PCR and quantitative REAL-time PCR of PML/RARa allows to follow the
individual kinetics of MRD and to identify patients with an imminent hematological relapse.
A standardized treatment for patients with relapsed APL has not yet been established. With
arsenic trioxide (ATO) monotherapy remission rates over 80% were achieved and long-lasting
molecular remissions are described. The drug was mostly well tolerated. ATO exerts a dose
dependent dual effect on APL blasts, apoptosis in higher and partial differentiation in lower
concentrations. ATO was also successfully administered before allogeneic and autologous
transplantation. ATO is approved for the treatment of relapsed and refractory APL in Europe
and in the USA.
After remission induction, there are several options for postremission therapy Previous
studies shows that risk of relapse is higher in patients treated with ATO postremission in
monotherapy , than in other that receive ATO plus chemotherapy or transplantation (TPH).
Also, compared with chemotherapy, ATO induction and consolidation has a favorable impact in
posterior response to transplantation. It is due to a low toxicity or a best quality of
remission to TPH. It seems better, for these reasons, the intensification with TPH
(autologous or allogenic) in patients with relapsed APL treated with ATO. For another hand,
patients no candidates to TPH can be treated with ATO combined with other active agents in
APL, as ATRA, anthracyclines o Mylotarg