Interim Anaiysis of Intention To Treat Analysis, “Multicenter AML-2000 Trial” Based on Cytogenetics Risk Factors.

Abstract

The result of cytogenetics is one of the most important prognostic factors on the prognosis of AML. HDAC, auto PBPCT and allogeneic BMT after 1 or 2 times of post remission therapy based on 4 prognostic groups(APL: Acute promyelocytic leukemia, GPG: Good prognosis group, IPG: Intermediate prognosis group, PPG: Poor prognosis group by MRC definition) were underwent based on cytogenetics data. We studied CR, relapse, toxic death, DFS and OS. Inclusion criteria were age<65, PS<3 with reasonable organ functions in de novo AML, secondary AML and RAEB-T. The aims of this prospective intention to treat analysis was to compare the CR, recovery kinetics, DFS and OS by giving different therapies of intensity in the different prognostic groups based on cytogentics data.Three plus seven(Idarubicin 12mg/m2(D1–D3), Ara-C 100mg/m2(D1–D7)) were given to de novo AML, secondary AML and RAEB-T. Intermediate dose(8gm/m2) of Ara-C was given followed by HDAC or auto PBPCT to the patients with GPG(t(8:21) & inv(16)). Three times of post remission therapy including HDAC, or auto PBPCT were given to the patients with IPG or PPG(−5, −7, del 5q, complex). If HLA-identical sibling was available, then allo BMT was underwent after 1st post-remission therapy. In cases of APL, three times of post-remission therapy with idarubicin alone were given. ATRA was given to APL group during remission induction therapy and after post-remission maintenance period for 2 years.Up to Mar., 2005, 422 patients(18 centers) were enrolled. Median follow-up was 48months. Among them, 92.3% was de novo AML, and APL, GPG, IPG and PPG were 10.0%, 21.6%, 51.4%, and 14.7% respectively. Overall CR after 1st induction(3+7) were 69.9%(APL: 87.2%, GPG: 84.7%, IPG: 63.8%, PPG: 55.66%, P<0.01). Relapse rate was 12.8%(APL), 40.5%(GPG), 40.5%(IPG) and 45.6%(PPG) respectively(P<0.01). Toxicities profiles including mucositis, hepatic, cardiac and bleeding episodes were similar on 3 different therapy modalities(HDAC, auto PBPCT and allo BMT).In conclusions, this trial seems to be tolerable in terms of toxicities after induction and during post remission therapies. Among GPG, there were no significant statistical differences on OS and LFS in all the therapy modalities(ie, HDAC, Auto, Allo). In IPG, auto arm had a tendency of superior OS and LFS comparing to HDA & allo arm. In PPG, there was significant surperior LFS in allo arm. There were no statistical differences on OS in all the therapy modalities in PPG. This intention to treattrial, which had started in Jan, 2000, has been going on until now. Through this risk based trial using cytogenetics, we might be able to find optimal post-remission therapies for different risk groups with less toxicities.