급성 전골수구성백혈병에서 all-trans retinoic acid의 효과

Abstract

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.