Most patients with APL are first treated with ATRA combined with chemo
The relapse rate is lower with ATRA/ATO with a cure rate of 99%, the side effects are less especially the hematotoxicy and you save the maintenance therapy
APL is heterogenous disease so you need to assess risk profile of the disease prior to making a decision how to treat patients. ATRA+ATO is new gold standard for low/intermediate risk APL as an induction approach. This combination is excellent is preserving heart function from antracyclines, is less hematotoxic, but a bit more hepatotoxic. Generally, this combination is more effective and less toxic over AIDA protocol. High risk APL still need to be involved with antracyclines. Prof Alain K Burnett from Cardiff University has published his study with chemo free approach, in these patients setting, however he used GO which is off lable use. Most of the approaches still include dauno or Ida for high risk APL.
Thank you dear Ivan Petkovic, dear Walter Fiedler and Dear Abdul Khaleque for your valuable answers .... they are interesting and useful,,,,,
you can refer to the NEJM 2013 paper from the Lo Coco group and the australian paper (APML04, blood 2012, Corresponding Auth: John Seymour), ATO ATRA is at least equivalent if not superior to ATRA IDA in low risk APML. The Australian paper showed that Addition of ATO to ATRA IDA makes a difference also for high risk diseases
Thank you Dear Thomas Prebet for your kind and informative answer
Table1 in this review ( 1) omitted the cardiovascular toxic effects due to all-trans retinoic acid (ATRA) and arsenic trioxide frequently used for the treatment of acute promyelocytic leukemia (APL), which is the M3 subtype of acute myelogenous leukemia. Approximately 25% of APL cases treated with ATRA exhibit the retinoic acid syndrome, also referred to as the capillary leak syndrome due to the cytokines release from the differentiating myeloid cells. The retinoic acid syndrome typically occurs within 21 days since after the first treatment.(2,3) The cardiovascular symptoms of this syndrome include the pericardial effusion and the significant decrease in the left ventricular ejection fraction, leading to the systemic hypotension. There have been several case reports in which APL patients treated with ATRA exhibited lethal myocardial infarction with the intra-cardiac thrombosis.(3,4) Furthermore, more than half of the APL patients treated with arsenic trioxide, who have been refractory to ATRA treatment, are reported to induce QT prolongation syndrome and enhances the risk of the emergence of the lethal ventricular arrhythmia characterized by Torsades de pointes.(5)
1. Moslehi JJ. Cardiovascular Toxic Effects of Targeted Cancer Therapies. N Engl J Med 2016;375:1457-67.
2. Tallman MS, Andersen JW, Schiffer CA, et al. Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood 2000;95:90-5.
3. Tallman MS, Andersen JW, Schiffer CA, et al. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med 1997;337:1021-8.
4. Cahill TJ, Chowdhury O, Myerson SG, et al. Myocardial infarction with intracardiac thrombosis as the presentation of acute promyelocytic leukemia: diagnosis and follow-up by cardiac magnetic resonance imaging. Circulation 2011;123:e370-2.
5. Soignet SL. Clinical experience of arsenic trioxide in relapsed acute promyelocytic leukemia. Oncologist 2001;6 Suppl 2:11-6.
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