Current study of APL treatment in China

Area of Science:

• Oncology
• Pharmacology
• Toxicology

Background:

• Natural arsenic sulfides, primarily As4S4 and As2S3 found in realgar and orpiment, are investigated for their therapeutic potential.
• Previous studies indicate NB4 cell lines and mouse models are more sensitive to As4S4 than As2O3 or As2S3, aligning with clinical observations in China.
• The excipient Seman platycladi can enhance oral absorption of arsenic compounds, increasing blood arsenic levels.

Purpose of the Study:

• To evaluate the efficacy and safety of As4S4 and As2S3 in treating patients with t(15;17) acute promyelocytic leukemia (APL).
• To compare treatment outcomes, including remission rates and relapse frequencies, between different arsenic-based regimens and conventional chemotherapy.
• To explore strategies for managing APL relapse and improving patient survival.

Main Methods:

• Clinical study involving 130 patients with t(15;17) APL treated with As4S4 and/or As2S3, with or without other antileukemic agents.
• Administration of As4S4 orally (P.O.), sometimes in combination with ATRA or chemotherapy, for newly diagnosed APL patients.
• Analysis of relapse factors, including resistant cell clones and decreased blood arsenic levels, and evaluation of salvage therapies like ASCT and cranial surgery.

Main Results:

• Both As4S4 and As2S3 monotherapy achieved complete remission (CR) in APL patients, including cytogenetic and PML-RAR reversion.
• Combination therapy with As4S4 and other agents resulted in lower relapse rates and improved long-term leukemia-free survival (LFS) and overall survival (OS) compared to As4S4 alone.
• High-dose chemotherapy was found to be unsafe and unnecessary; As4S4 with ATRA or chemotherapy demonstrated safety and efficacy in newly diagnosed APL.
• Relapse was associated with resistant clones or low blood arsenic levels; combination therapy with ATRA or modified preparations could address these issues.
• Autologous stem cell transplantation (ASCT) showed better outcomes than allogeneic SCT (allo-SCT) in relapsed patients.
• Prompt cranial surgery was critical for rescuing patients with intracranial hemorrhage.

Conclusions:

• Oral As4S4 and As2S3 are effective in inducing CR in t(15;17) APL, with combination therapies significantly reducing relapse rates.
• Arsenic-based treatments, particularly oral As4S4, offer a safer and more manageable alternative to high-dose chemotherapy for APL.
• Most t(15;17) APL patients can potentially be cured with optimized arsenic-based treatment strategies, including management of relapse and supportive care.