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Arsenic Trioxide (Trisenox^®) Therapy for Acute Promyelocytic Leukemia in the Setting of Hematopoietic Stem Cell Transplantation

^a Division of Hematology, Norris Cancer Center, University of Southern California at Los Angeles, Los Angeles, California, USA; ^b St. Joseph’s Hospital, Orange, California, USA; ^c M.D. Anderson Cancer Center, Houston, Texas, USA; ^d Cedars-Sinai Medical Center, Los Angeles, California, USA; ^e Washington University, Saint Louis, Missouri, USA

Correspondence: Dan Douer, M.D., Bone Marrow Transplantation Program, USC/Norris Cancer Center, 1441 Eastlake Avenue, Room 3460, Los Angeles, California 90033, USA. Telephone: 323-865-3145; Fax: 323-865-0060; e-mail: douer_d{at}mikey.hsc.usc.edu

The relapse-free survival of patients with acute promyelocytic leukemia (APL) has significantly increased during the last decade. The introduction of all-trans retinoic acid (ATRA) doubled the survival of patients with this disease. However, despite ATRA and anthracycline-based chemotherapy, 12%–30% of patients will still relapse. Arsenic trioxide (ATO) has demonstrated efficacy and safety in patients with first and subsequent relapsed or refractory APL, regardless of the disease-free interval. Treatment of relapsed and refractory patients with this novel therapy produces complete remission in 87% of patients and molecular remission in 83%. Studies have documented the efficacy of autologous and allogeneic transplantation as salvage therapy in relapsed and refractory APL. The introduction of ATO into the treatment regimen for APL has stimulated discussion on its role in the transplantation setting. Investigators recently met to discuss the issue and make recommendations regarding ATO therapy in patients who are in their second or subsequent complete remission and are candidates for transplantation. This article describes the pivotal studies of this novel agent, discusses risk factor stratification for relapse in patients with APL, and proposes protocols for treatment incorporating ATO therapy. In addition, it describes scientific issues in ongoing and proposed clinical trials of ATO therapy for this disease.

Key Words. Acute promyelocytic leukemia • Arsenic trioxide • Transplantation • Molecular remission

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