Advertisement

Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab

Yasmin Abaza, Hagop M. Kantarjian, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Susan O'Brien, William Wierda, Sherry Pierce, Mark Brandt, Deborah McCue, Rajyalakshmi Luthra, Keyur Patel, Steven Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Nitin Jain, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, David McCue, Jorge Cortes and Farhad Ravandi

Key points

  • Combination of ATRA, ATO, with or without GO is effective and safe for the treatment of newly diagnosed APL patients, including the high risk category.

  • Long term follow up suggests that the responses are durable with very rare relapses.

Abstract

The combination of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard risk newly diagnosed patients with acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamycin (GO) in high-risk patients. We examined the long-term outcome of newly diagnosed APL patients treated at our institution on three consecutive prospective clinical trials using the combination of ATRA, ATO, with or without GO. For induction all patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m2 on day 1) added to high risk patients (WBC > 10 x 109/L), as well as low risk patients who experienced leukocytosis during induction. Once in complete remission (CR), patients received 4 cycles of ATRA plus ATO consolidation. 187 patients, including 54 with high risk and 133 with low risk disease have been treated. The complete remission rate was 96% (52 of 54 in high risk, 127 of 133 in low risk). Induction mortality was 4% with only 7 relapses. Among low risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The five-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

  • Submitted September 7, 2016.
  • Accepted December 8, 2016.