All-trans retinoic acid therapy for newly diagnosed acute promyelocytic leukemia: Comparison with intensive chemotherapy

被引:20
作者
Asou, N
Adachi, K
Tamura, J
Kanamaru, A
Kageyama, S
Hiraoka, A
Omoto, E
Sakamaki, H
Tsubaki, K
Saito, K
Ohno, R
机构
[1] NAGOYA UNIV,SCH MED,DEPT INTERNAL MED 1,NAGOYA,AICHI 466,JAPAN
[2] GUNMA UNIV,SCH MED,DEPT INTERNAL MED 3,MAEBASHI,GUMMA 371,JAPAN
[3] HYOGO MED UNIV,DEPT INTERNAL MED 2,NISHINOMIYA,HYOGO,JAPAN
[4] MIE UNIV,SCH MED,DEPT INTERNAL MED 2,TSU,MIE 514,JAPAN
[5] CTR ADULT DIS,DEPT INTERNAL MED 5,OSAKA 537,JAPAN
[6] OKAYAMA UNIV,SCH MED,DEPT INTERNAL MED 2,OKAYAMA 700,JAPAN
[7] TOKYO METROPOLITAN KOMAGOME HOSP,DEPT INTERNAL MED,TOKYO,JAPAN
[8] KINKI UNIV,SCH MED,DEPT INTERNAL MED 3,OSAKA 589,JAPAN
[9] DOKKYO UNIV,SCH MED,DEPT INTERNAL MED 3,TOCHIGI,JAPAN
[10] HAMAMATSU MED SCH,DEPT INTERNAL MED 3,HAMAMATSU,SHIZUOKA,JAPAN
关键词
acute promyelocytic leukemia; all-trans retinoic acid; differentiation therapy; chemotherapy;
D O I
10.1007/s002800051058
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We analyzed the results of treating patients with newly diagnosed acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) in the JALSG AML-92 study and compared them with those of the AML-87 and AML-89 studies, which consisted of standard chemotherapy. In the AML-92 study, patients were scheduled to receive 45 mg/ m(2) oral ATRA daily until achievement of a complete remission (CR). If patients had initial leukocyte counts of > 3.0 x 10(9)/l, they received 40 mg/m(2) daunorubicin (DNR) for 3 days and 200mg/m(2) behenoyl cytarabine (BHAC) for 5 days in addition to ATRA. During remission induction therapy, if the patients showed peripheral blood myeloblast and promyelocyte counts of >1.0x10(9)/l, they received additional DNR and BHAC on the same schedule. After achievement of a CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. Of 196 evaluable patients, 173 (88%) achieved a CR: 59 of 62 (95%) treated with ATRA alone, 41 of 49 (84%) treated with ATRA plus later chemotherapy, 63 of 73 (86%) treated with ATRA plus initial chemotherapy, and 10 of 12 (83%) treated with ATRA plus both initial and later chemotherapy The CR rate in AML-92 was significantly higher than that in AML-89, but not than that achieved in AML-87. In addition, the early mortality and relapse rates in AML-92 were significantly lower than those in AML-89, but were not than those in AML-87. At a median follow-up of 36 months the predicted 4-year eventfree survival (EFS) rate for 196 evaluable patients and the 4-year disease-free survival (DFS) rate for the CR cases were 54% and 62%, respectively. There was a significant difference in DFS between AML-92 and AML-87 (P = 0.0418) but not between AML-92 and AML-89 (P= 0.0687). In contrast, significant differences in EFS between AML-92 and both AML-87 (P = 0.0129) and AML-89 (P = 0.005) were observed. These results suggest that non-cross-resistant therapy combined with ATRA and intensive chemotherapy for APL contributes synergistically to the significant improvement in EFS.
引用
收藏
页码:S30 / S35
页数:6
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