Treatment of Acute Promyelocytic Leukemia With All-Trans Retinoic Acid (ATRA) and Idarubicin (AIDA)
Status:
Completed
Trial end date:
2007-11-01
Target enrollment:
Participant gender:
Summary
The purpose of this study is to evaluate the efficacy of all-trans retinoic acid (ATRA) and
idarubicin (AIDA) with a dose reduction in patients older than 70 years of age in the
remission induction of acute promyelocytic leukemia (APL).
With regard to the induction, the excellent results obtained by the combination of ATRA and
idarubicin (AIDA), especially in terms of antileukemic efficacy (1% of resistance), do not
support the introduction of substantial changes in this combination. However, given that most
of the induction failures were caused by complications, especially of a hemorrhagic nature,
and that these had a major impact in the hyperleukocytic forms and in patients older than 70
years of age, the induction was modified as follows:
1. Reduction of idarubicin dose in patients older than 70 years of age (three days instead
of four);
2. Early administration of corticosteroid therapy in all patients as ATRA syndrome
prophylaxis. A preliminary analysis of the Italian Group for Adult Hematologic Diseases
(Gruppo Italiano Malattie Ematologiche dell'Adulto, GIMEMA) has shown that low dose
prednisone use in a prophylactic manner appears to reduce the incidence and severity of
the ATRA syndrome, which could also have a favorable impact on the hemorrhagic mortality
(non-published data); and
3. Treatment of the hyperfibrinolysis with an antifibrinolytic agent (tranexamic acid). It
has been recently reported that APL cells present abnormally high levels of annexins
(especially annexin II), and that these levels may provide the fundamental mechanism for
the hemorrhagic complications in APL by increasing the production of t-PA dependent
plasmin. These findings provide new reasons for the introduction of tranexamic acid in
the hemorrhagic prophylaxis of APL.