All-trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL)

Hematol Oncol. 1996 Sep;14(3):147-54. doi: 10.1002/(SICI)1099-1069(199609)14:3<147::AID-HON582>3.0.CO;2-3.

Abstract

Acute promyelocytic leukemia is characterized by the reciprocal translocation of chromosomes 15 and 17. All-trans retinoic acid (ATRA) efficiently induces differentiation of the abnormal promyelocytes. In this study, we had used ATRA as the primary induction therapy for 17 newly diagnosed patients, and as the salvage therapy for 11 patients who relapsed from or were resistant to chemotherapy. All patients received subsequent consolidation chemotherapy. Complete remission (CR) rate, early death rate (within 28 days of diagnosis) were then compared to an historical control of 50 APL patients treated with combination chemotherapy; and event-free survival of the 17 newly diagnosed patients was compared to the historical control. In the ATRA group, 26 of the 28 patients (93 per cent) attained complete remission. Two of 28 (7 per cent) died within 28 days of ATRA therapy. There was no case of primary resistance to ATRA. Combination chemotherapy was added to ATRA in five patients due to rapidly increasing leucocyte count. There was one case of retinoic acid syndrome which resolved with steroid. When compared to the 50 cases of historical control, there is significant improvement in the overall CR rate (92 per cent versus 59 per cent, p = 0.001) and a significant reduction in the early mortality rate (7 per cent versus 41 per cent, p = 0.001). Moreover, when the survival result of the 17 newly diagnosed patients were compared with the control, there is a significant improvement in the projected EFS at 3 years (64 per cent versus 25 per cent, p = 0.007). In conclusion, ATRA was shown to improve the CR rate, reduce induction mortality and significantly prolong the event-free survival.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cohort Studies
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Disease-Free Survival
  • Female
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / mortality
  • Life Tables
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Oncogene Proteins, Fusion / analysis
  • Prospective Studies
  • Remission Induction
  • Salvage Therapy
  • Survival Analysis
  • Treatment Outcome
  • Tretinoin / therapeutic use*

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • Cytarabine
  • Tretinoin
  • Daunorubicin