ABSTRACT
Introduction: The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) to clinical practice revolutionized the APL therapy and allowed development of chemotherapy-free regimen with high success rates in low- and intermediate-risk patients. Although APL is now a curable disease, the early deaths are common, up to 30% in some studies.
Areas covered: Factors associated with high induction deaths such as delays in starting ATRA therapy, differentiation syndrome, unrecognized fluid overload, and coagulopathy were discussed. We searched the PubMed for relevant articles from inception to 2019. We summarized current and emerging treatment options for patients with low and high-risk APL and highlighted relevant clinical points that need to be monitored closely during induction therapy.
Expert opinion: Although patients universally respond to ATRA + ATO based therapy, induction death still remains as one of the main obstacles of APL therapy. Efforts in this area must focus to facilitate prompt diagnosis, earlier initiation of therapy, and vigorous clinical monitoring to prevent expected complications of APL and its therapy. Oral arsenic compounds that have been shown to be equally effective may substitute IV formulation, in combination with ATRA, thus allowing a complete oral management of APL.
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Article highlights
Clinicians should have a high level of suspicion for APL in patients presenting to the clinic or emergency room with cytopenias and coagulopathy
Immediate administration of ATRA at the initial suspicion of APL is of extreme importance, and the clinician should not postpone ATRA therapy pending molecular or cytogenetic confirmation of the diagnosis
Patients with high-risk APL can be treated using ATRA + ATO similar to lower risk APL with addition of gemtuzumab ozogamicin or idarubicin early during induction
Fluid overload is common during induction phase, but it is commonly overlooked. Patients should be weighted daily on a bedside scale and diuretics should be administered liberally to maintain admission weight and achieve a balanced intake/output daily throughout induction course
Oral arsenic compounds are as effective as IV formulations when used in combination with ATRA in patients with newly diagnosed APL
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.