Current study of APL treatment in China

Abstract

Natural As₄S₄ and As₂S₃ are major components in realgar and orpiment, which also contain small amount of As₂O₃ and other toxic materials. Liu YF showed with us that NB4 cell line and its mice model were more sensitive to As4S4 than to As₂O₃ and As₂S₃. That was in agreement with the clinical data available from China. Wang FR and we proved in mice and in clinical pharmaceutical study that groundSeman platycladi as an excipient can appreciably increase the blood level of arsenic when taken P.O. together with As₄S₄. Our clinical study with 130 patients with t(15;17) APL showed both As₄S₄ and As₂S₃ alone were very effective in CR induction, including cytogenetic remission and PML-RAR reversion, yet the relapse rate was higher in the group treated by As₄S₄ alone than in the group treated together with other autileukemic agents, either together or in sequence. In the later group, LFS for 1 and 6 years was 96.7% and 87.4%, and the over-all survival for 1 and 6 years was 98.9% and 93.9%. High dose chemotherapy was proven to be not only unsafe but also unnecessary. In newly diagnosed APL patients with neutropenia, CR could be safely achieved by As₄S₄ P.O. and/with ATRA. Chemotherapy was then followed. In patients with leukocytosis, chemotherapeutic agents such as hydroxyurea or harringtonine was added at the beginning and then followed by anthracycline and asparaginase. The reasons of APL relapse after patients receiving As₄S₄ P.O. were: ① emergence of a resistant cell clone showing additional chromosomal abnormalities other than t(15;17); ② decrease of blood As level. The resistant APL case could respond favorably to combination of As₄S₄ P.O. together with ATRA. The blood level of As could be raised by modification of the preparation under investigation. Allogeneic stem cell transplantation (allo-SCT) is the last option in relapsed patients, became autologous stem cell transplantation (ASCT) has a significantly better outcome. In a few hospitals ASCT was performed early in the CR1. In rare cares, patients were referred with intra-cranial hemorrhage. CT or EMR scan was done urgently at this instance. Cranial surgery carried out without a minute of delay resulted in the rescue and long survival of patient, while delay of surgery had resulted in irreversible damage of Pons/Medulla oblongata and ended in death. As₂O₃ IV had been used with success in mentally unclear patients not suffering from intra-cranial hemorrhage. Although no parallel clinical trial has been done to compare the efficacy of As₂O₃ and As₄S₄, yet the fact was it was easier for doctors and patients to carry out and receive maintenance treatment with oral As₄S₄ rather than with As₂O₃. According to the data and principles above, most of the t(15;17) APL patients can be cured. *** DIRECT SUPPORT *** A00RC002 00019