14. Acute Promyelocytic Leukemia: Manifestations and Therapy

  1. Stefan Faderl MD Associate Professor and
  2. Hagop Kantarjian MD Chairman Professor
  1. Sylvain Thépot,
  2. Lionel Ades and
  3. Pierre Fenaux

Published Online: 4 JAN 2011

DOI: 10.1002/9781444327359.ch14

Leukemias: Principles and Practice of Therapy

Leukemias: Principles and Practice of Therapy

How to Cite

Thépot, S., Ades, L. and Fenaux, P. (2010) Acute Promyelocytic Leukemia: Manifestations and Therapy, in Leukemias: Principles and Practice of Therapy (eds S. Faderl and H. Kantarjian), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444327359.ch14

Editor Information

  1. Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

Author Information

  1. Service d'hmatologie clinique, Hopital Avicenne (Assistance Publique-Hopitaux de Paris) and Paris 13 University, Bobigny, France

Publication History

  1. Published Online: 4 JAN 2011
  2. Published Print: 26 NOV 2010

ISBN Information

Print ISBN: 9781405182355

Online ISBN: 9781444327359

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Keywords:

  • acute promyelocytic leukemia;
  • all trans retinoic acid;
  • arsenic

Summary

Acute promyelocytic leukemia (APL) is a specific type of acute myeloid leukemia (AML) characterized by the morphology of its blast cells, the t(15;17) translocation that fuses the PML gene on chromosome 15 to the retinoic acid receptor alpha (RARα) gene on chromosome 17 and a coagulopathy combining disseminated intravascular coagulopathy (DIC) and fibrinolysis. Over the last 15 years, the advent of all-trans retinoic acid (ATRA), and more recently of arsenic trioxide, have greatly improved the therapeutic approach of acute promyelocytic leukemia (APL), yielding about 95% complete remission (CR) rates and a minimum of 80% cure rates. The combination of ATRA and conventional anthracycline-based chemotherapy (CT) has clearly demonstrated its superiority over CT alone (in terms of CR rate, relapse and survival) in newly diagnosed APL. Several randomized studies strongly suggest that prolonged maintenance treatment with ATRA and low-dose CT, and possibly very early introduction of anthracycline CT during induction treatment, can reduce the incidence of relapse. Real-time polymerase chain reaction (RT-PCR)-analysis of the PML-RARα transcript is an important tool to measure minimal residual disease in APL, which helps in the management of individual patients with baseline white blood cell (WBC) counts > 10 G/L (who remain at higher risk of early death and relapse) to benefit from intensive initial supportive care, especially massive platelet transfusions, and reinforcement of post-induction treatment (by AraC or arsenic derivatives); maintenance treatment also appears to play a major role in this subset. Arsenic derivatives can also play a role in first-line treatment in non-hyperleukocytic forms, especially if one wants to reduce the intensity of chemotherapy, such as in elderly patients. A large proportion of patients with APL who relapse after ATRA and CT can be durably salvaged by arsenic derivatives followed by allogeneic or autologous stem cell transplantation, provided the transplant (in the autologous setting) is RT-PCR-negative for the PML-RARα transcript at the time of stem cell collection.