Background: All-trans retinoic acid(all-trans RA) represents a major conceptual and
practical advance in the treatment of patients with acute promyelocytic leukemia(APL).
The initial biologic effects of this agent are characterized by differentiation of the
malignant cells into phenotypically mature cells before their eventual elimination,
presumably via programmed cell death. However, the proper management of patients
who present with or develop leukocytosis during remission induction with all-trans RA
is not established. Thus we reviewed our experiences to evaluate the effect of all-trans
RA and the role of leukapheresis for all-trans RA-induced leukocytosis.
Method: From March 1990 to December 1994, we have analyzed the effect of all-trans
RA and induction chemotherapy and the role of leukapheresis for all-trans RA-induced
leukocytosis in 32 patients with newly diagnosed APL retrospectively.
Results :
1) Thirteen Patients were allocated to the all-trans RA group and nineteen to the
chemotherapy group. The two groups were well balanced for all initial characteristics.
2) In the all-trans RA group, nine patients(69.2%) achieved complete remission(CR)
and 3(23.0%) had early death, compared with 6(31.6%) and 7(36.8%), respectively, in the
chemotherapy group. The difference in CR rate between the two groups was
significant(P=0.036). The duration of coagulopathy was significantly reduced in the
all-trans RA group, compared with the chmotherapy group(P=0.007).
3) Ten of thirteen patients(76.9%) who were treated with all-trans RA met the
European leukocyte criteria that would have require additional treatment to prevent the
hyperleukocytic syndrome. Seven of thirteen patients(53.8%) underwent one-to-three
leukaphereses, and three patients(23.1%) received low-dose chemotherapy. Five of seven
patients(71.4%) who underwent leukaphereses achieved CR, and two patients(28.6%) died
from intracranial hemorrhage.
4) The Kaplan-Meier estimate of event-free survival(EFS) waIn 65.4±13.1% at 1 year
in the all-trans RA group versus 25.3± 10.2% in the chemotherapy group. The
difference was significant(p=0.04).
Conclusion : These results suggest that the use of all-trans RA induces a higher CR
rate and better EFS than chemotherapy in patients with APL. Even with all-trans RA,
the major cause of death in patients with APL is still intracranial hemorrhage. Thus
lusher studies are critically needed to identify and optimize the management of patients
who are at highest risk for early fatal hemorrhage.

Keywords: All-trans retinoic acid, Acute promyelocytic leukemia, Leukapheresis