A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RARalpha transcript after consolidation therapy: the Japan Adult Leukemia Study Group (JALSG) APL97 study.
To examine the efficacy of intensified maintenance chemotherapy, we conducted a prospective multicenter trial in adult patients with newly diagnosed acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Of the 302 registered, 283 patients were assessable and 267 (94%) achieved complete remission. Predicted 6-year overall survival in all assessable patients and disease-free survival in patients who achieved complete remission were 83.9% and 68.5%, respectively. A total of 175 patients negative for PML-RARalpha at the end of consolidation were randomly assigned to receive either intensified maintenance chemotherapy (n = 89) or observation (n = 86). Predicted 6-year disease-free survival was 79.8% for the observation group and 63.1% for the chemotherapy group, showing no statistically significant difference between the 2 groups (P = .20). Predicted 6-year survival of patients assigned to the observation was 98.8%, which was significantly higher than 86.2% in those allocated to the intensified maintenance (P = .014). These results indicate that the intensified maintenance chemotherapy did not improve disease-free survival, but rather conferred a significantly poorer chance of survival in acute promyelocytic leukemia patients who have become negative for the PML-RARalpha fusion transcript after 3 courses of intensive consolidation therapy.
Asou
Norio
N
Department of Hematology, Kumamoto University School of Medicine, Kumamoto, Japan. ktcnasou@gpo.kumamoto-u.ac.jp
Kishimoto
Yuji
Y
Kiyoi
Hitoshi
H
Okada
Masaya
M
Kawai
Yasukazu
Y
Tsuzuki
Motohiro
M
Horikawa
Kentaro
K
Matsuda
Mitsuhiro
M
Shinagawa
Katsuji
K
Kobayashi
Tohru
T
Ohtake
Shigeki
S
Nishimura
Miki
M
Takahashi
Masatomo
M
Yagasaki
Fumiharu
F
Takeshita
Akihiro
A
Kimura
Yukihiko
Y
Iwanaga
Masako
M
Naoe
Tomoki
T
Ohno
Ryuzo
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007564:Japan; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014212:Tretinoin / Q000627:therapeutic use
D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin