Affiliations 

  • 1 The University of Hong Kong, Hong Kong, Hong Kong
  • 2 Queen Mary Hospital, Pokfulam, NT, Hong Kong
  • 3 National Taiwan University Hospital, Taipei, Taiwan
  • 4 National Taiwan University Hospital, Taipei City, Taiwan
  • 5 Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  • 6 National University Cancer Institute Singapore, Singapore, Singapore
  • 7 Universiti Malaya, Kuala Lumpur, Malaysia
  • 8 Sunway Medical Centre, Selangor, Malaysia
  • 9 Hong Kong University, Hong Kong, Hong Kong
  • 10 University of Hong Kong, Hong Kong, Hong Kong
  • 11 The University of Hong Kong, Hong Kong, China
  • 12 Yong Loo Lin School of Medicine, Singapore, Singapore
  • 13 Queen Mary Hospital, Hong Kong, China
  • 14 University of Hong Kong, Hong Kong, China
Blood Adv, 2024 Dec 18.
PMID: 39693517 DOI: 10.1182/bloodadvances.2024014999

Abstract

The Acute Promyelocytic Leukemia Asian Consortium analyzed a contemporaneous cohort of newly-diagnosed APL patients treated with and without frontline arsenic trioxide (ATO) in six centers. The objectives were to define the impact of ATO on early deaths and relapses, and its optimal positioning in the overall treatment strategy. In a 21.5-year period, 324 males and 323 females at a median age of 45.5 (range: 18.1-91.8) years (low/intermediate risk, N=448; high-risk, N=199) were treated. Regimens included frontline all-trans retinoic acid (ATRA)/chemotherapy and maintenance with/without ATO (N=436); ATRA/intravenous-ATO/chemotherapy (ATRA/i.v.-ATO; N=61); and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; N=150). The ATRA/chemotherapy group, compared with the ATO-containing (ATRA/i.v.-ATO and oral-AAA) groups, had significantly more frequent early deaths within 60 days (8.3% versus 3.3%; P=0.05); inferior 60-day survival (91.7% versus 98.4%/96%; P<0.001); inferior 5-year relapse-free survival (RFS) (76.9% versus 92.8%/97.8%; P<0.001) and inferior 5-year overall survival (OS) (84.6% versus 91.4%/92.3%; P=0.03). Addition of oral-ATO maintenance could partly mitigate the inferior 5-year RFS resulting from omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance versus ATRA/chemotherapy/ATO maintenance versus ATRA/i.v.-ATO versus oral-AAA: 71.1% versus 87.9% versus 92.8% versus 97.8%, P<0.001). The favorable survival impacts of ATO were observed in both low/intermediate-risk and high-risk patients, so that conventional risks (high leucocyte and low platelet counts) were overcome. Therefore, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. Its benefits were most obvious in frontline treatment, but were still observed during maintenance. (ClinicalTrials.gov Identifier: NCT04251754).

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.