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 ground Seman 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.