CHICAGOUsing all-trans retinoic acid (ATRA) to both induce
remission and for maintenance makes acute promyelocytic leukemia
(APL) potentially the most curable subtype of adult acute myeloid
leukemia, said Martin S. Tallman, MD, at the American Society of
An associate professor of medicine at Northwestern University Medical
School and member of the Robert H. Lurie Comprehensive Cancer Center
in Chicago, Dr. Tallman reported on data from the long-term follow-up
of a collaborative study. Participating in the study were the Eastern
Cooperative Oncology Group, the National Cancer Institute of Canada-Clinical
Trials Group, the Cancer and Leukemia Group B, the Southwest
Oncology Group, the Childrens Cancer Group, and the Pediatric
The researchers compared the four possible combinations of two
induction and consolidation treatments and two maintenance
treatments. The 350 APL patients were given an induction treatment
that consisted of either:
- ATRA at a dose of 45 mg/m² per day until a complete
remission occurred or for a maximum of 90 days; or
- daunorubicin (Cerubidine) at 45 mg/m²per day by
intravenous bolus on days 1 to 3 and cytarabine (ara-C [Cytosar and
others] ) 100/m² by continuous infusion on days 1 to 7.
(Children less than 3 years old received a reduced dose.)
All patients who achieved complete remission then received two cycles
of consolidation therapy. First, they went through another cycle of
the drugs given in the induction phase. Next, each received a 1-hour
infusion of cytarabine at 2 g/m² twice a day for 4 days and an
intravenous infusion of daunorubicin at 45 mg/m² on days 1 and
2, except children less than 3, who again received a smaller dose of
daunorubicin and cytarabine.
Patients who were still in complete remission after both
consolidation cycles moved into the maintenance phase. They were
randomly assigned to one of two groups:
- observation alone or
- 45 mg/m² of oral ATRA each day for 1 year.
Survival Data Diverge
Of the 350 patients, 250 achieved complete remission, including 70%
of patients whose induction therapy was daunorubicin-cytarabine and
73% of patients induced by ATRA. Survival data, however, revealed a
significant difference between these two groups. The best
outcome is achieved when ATRA is given during induction and
maintenance, Dr. Tallman said.
For patients with daunorubicin-cytarabine as induction therapy,
disease-free survival after 5 years was 47% among those on ATRA
during maintenance and only 10% among those merely observed. For
patients with ATRA as induction therapy, disease-free survival after
5 years was 74% among those on ATRA also during maintenance and 51%
among those observed.
Twenty of the 250 patients relapsed after 2 years of remission, with
the longest remission among the patients relapsing late 4.3 years
before relapse. Only 1 patient of the 20 was in the ATRA-ATRA group.
Dr. Tallman concluded that the excellent results produced by ATRA
given both during induction and maintenance means that APL has become
potentially more curable than other acute myeloid leukemias. In the
question-and-answer session, he stated that he believes that
maintenance therapy is important for patients with APL.