Long-term outcome of 31 cases of refractory acute promyelocytic leukemia treated with compound realgar natural indigo tablets administered alternately with chemotherapy

Abstract

Abstract. The aim of the present study was to investigate the long-term survival of patients with refractory acute promyelocytic leukemia (APL) that were administered alternately with compound realgar natural indigo tablet (CRNIT) treatment and chemotherapy. In total, 31 patients with refractory APL were administered with CRNIT treatment alternately with chemotherapy. The complete remission (CR) and relapse rates were estimated by bone marrow (BM) examination. The expression of the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion protein and the apoptosis rate in the retinoic acid (RA)-resistant NB4-R1 cell line administered with CRNIT treatment in vitro were measured by western blot analysis and flow cytometry, respectively. The patients were followed up for 12-60 months, with a median follow-up time of 43 months. The total continuous CR rate was 90.32% (28/31), and the duration of response was between 10.3 and 60 months (median, 42.4 months). The total relapse rate was 9.68% (3/31), and the median time of relapse was 13 months (range, 8-27 months). During the treatment with CRNITs, there was no evident BM depression and only limited side-effects were experienced. Additionally, in vitro cell molecular biology results revealed that CRNIT treatment resulted in a marked induction of apoptosis and degradation of the PML-RARα fusion protein.The present results revealed that CRNIT treatment in combination with chemotherapy is an effective and feasible therapy for the treatment of patients with refractory APL.

Arsenic disulfide‑induced apoptosis and its potential mechanism in two‑ and three‑dimensionally cultured human breast cancer MCF‑7 cells

“…As 2 S 2 , which shows similar efficacy and fewer adverse effects (14,15), is much less toxic than arsenic trioxide and other common arsenic compounds, including sodium arsenite and arsenate (14,38), and has been considered as an alternative oral arsenic agent for cancer treatment. In China, As 2 S 2 has already been approved for clinical use in the treatment of leukemia (16)(17)(18)39). A series of clinical studies and trials proved that treatment with As 2 S 2 was well tolerated, with only moderate side-effects in patients suffering from APL (13,39,40).…”

“…Arsenic disulfide (As 2 S 2 ), as the predominant active ingredient of realgar, also known as 'Xiong-Huang' in traditional Chinese medicine, is considered to be a candidate for the treatment of several types of malignancies; it exhibits relatively low toxicity, and has the advantage of being orally administered (10,(13)(14)(15). A series of basic and clinical studies have reported the antitumor effects of As 2 S 2 in different types of malignancies, particularly hematopoietic tumors such as APL (13,(16)(17)(18)(19). Recently, there is increasing evidence to support that As 2 S 2 has the ability to induce apoptosis and inhibit the growth of hematopoietic and solid tumor cell lines, such as human lymphoma cell lines (20), cervical cancer cell lines (21), human hepatocellular carcinoma cells (22), and human osteosarcoma cell lines (23).…”

Antitumor effects of arsenic disulfide on the viability, migratory ability, apoptosis and autophagy of breast cancer cells

“…Arsenic disulfide (As 2 S 2 ) is an orange-red crystalline mineral and the principal effective component of realgar, and has been used extensively to treat various diseases in ancient China and Europe ( 1 ). In recent decades, a series of studies have revealed the marked therapeutic potential of As 2 S 2 in hematopoietic tumors, particularly acute promyelocytic leukemia (APL) ( 2 – 4 ). In addition, recent evidence has revealed the potent anticancer effect of As 2 S 2 against various human solid cancer cell lines, but with markedly decreased toxicity in normal somatic cells ( 5 – 7 ).…”

Observation of clinical efficacy and toxic and side effects of pirarubicin combined with cytarabine on acute myeloid leukemia

“…It is suggested that pirarubicin-based treatment regimen may have less toxic and side effects and higher safety in AML patients. Mitoxantrone is found to have a higher response rate to AML at a high dose, but it also leads to decrease in EF, increase in Tei index, and significant decrease in GLS and GCS, as well as higher E/E ratio and lower E/A ratio, which show that the ventricular diastolic ability is also damaged (31). Other studies found that mitoxantrone also causes leukopenia, erythropenia and thrombocytopenia in blood, and even treatment-related acute leukemia in the treatment of patients with multiple sclerosis (32).…”