title: Multi-institutional study of all-trans-retinoic acid as a differentiation therapy of refractory acute promyelocytic leukemia. Leukaemia Study Group of the Ministry of Health and Welfare.
abstract: We treated 70 acute promyelocytic leukemia (APL) patients with daily oral 45 mg/m2 all-trans-retinoic acid (ATRA) in two multi-institutional prospective studies. Of 64 evaluable patients, 21 were refractory to initial induction chemotherapy; 10 were refractory to salvage chemotherapy; 17, five, and four were in the first, second and, third relapse, respectively; and seven were previously untreated due to old age. In the first study with ATRA from China, 18 out of 22 (82%) evaluable patients achieved complete remission (CR). Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01); < 100/microliters in 17 out of 18 CR cases, and > or = 200/microliters in all failure cases. In the second study with ATRA from Hoffmann-La Roche, if initial leukemia cell counts were more than 200/microliters, chemotherapy was first given and then ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. Morphological evidence of differentiation was noted in all CR cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 20-month predicted disease-free survival rate is 76% for cases achieving their first CR with ATRA. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage, and high serum triglyceridemia.
authors.affiliation: Department of Medicine, Nagoya University School of Medicine, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Ohno
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: H
authors.initials: H
authors.lastname: Fukutani
authors.forename: T
authors.initials: T
authors.lastname: Naoe
authors.forename: T
authors.initials: T
authors.lastname: Ohshima
authors.forename: T
authors.initials: T
authors.lastname: Kyo
authors.forename: N
authors.initials: N
authors.lastname: Endoh
authors.forename: T
authors.initials: T
authors.lastname: Fujimoto
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: A
authors.initials: A
authors.lastname: Hiraoka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002648:Child; D005260:Female; D006801:Humans; D007564:Japan; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D015996:Survival Rate; D014212:Tretinoin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014212:Tretinoin