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

Leukemia. 1993 Nov;7(11):1722-7.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cell Differentiation / drug effects
  • Child
  • Female
  • Humans
  • Japan
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / mortality
  • Leukemia, Promyelocytic, Acute / pathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Remission Induction
  • Survival Rate
  • Tretinoin / adverse effects
  • Tretinoin / therapeutic use*


  • Tretinoin