A Case of Relapsed Acute Promyleocytic Leukemia Induced Remission with Arsenic Trioxide(As2O3)

Acute promyelocytic leukemia(APL) is a unique entity in the spectrum of acute myelogenous leukemia. It has several characteristic features, including distinctive morphology, chromosomal translocation, t(15:17), disseminated intravascular coagulation and effect on retinoic acid. Retinoic acid which is a derivative of vitamin A induces differentation of APL cells in vitro and in vivo, but its cessation induces relapse of APL. Arsenic trioxide(AszOz) can induce clinical remission in patients with APL, including those who have relapsed after retinonic acid treatment. We report a case of a 9-year-old male with APL who had relapsed after cessation of retinoic acid treatment. The patient successfully achieved remission following treatment with AsO. Arsenic trioxide treatment would be an effective and relatively safe drug in childhood APL patients refractory to retinoic acid.

Anticancer Effect of Arsenic Trioxide in Acute Promyelocytic Leukemia

PURPOSE: Acute promyelocytic leukemia (APL or AML, M3) represents an unique model for cancer research in terms of biological and clinical features. Since 1988, it has been widely confirmed that all-trans retinoic acid (ATRA) can induce complete clinical remission in over 85% of APL patients by a differentiation process, with PML-RARalpha protein possibly being the direct target of ATRA. However, ATRA treatment has two clinical limitations, namely, retinoic acid syndrome and retinoic resistance. Recently, it has been shown that arsenic trioxide used in some traditional Chinese remedy is very effective in retinoic resistant APL treatment. We tried to observe arsenic effect on cell lines and APL patient cells. MEHTODS: We investigated arsenic trioxide-induced apoptosis on APL, HL60, K562, KPH1 cell lines through MTT assay, DNA fragmentation assay and morphologic features. RESULTS: In MTT assay, cell survival rate decreased as the concentration of arsenic trioxide increased. In DNA fragmentation assay with HL60 cell line, DNA fragmentation was more frequent in high concentrations of arsenic trioxide than in low concentrations. During arsenic trioxide treatment, the morphologic change in bone marrow cells of APL patient, included nuclear differentiation and dark cytoplasmic granule during arsenic trioxide treatment. Serum arsenic reached peak level at 4hr after injection. We experienced a case of a 9-year-old male with APL who had relapsed after cessation of retinoic acid treatment. The patient successfully achieved remission following arsenic trioxide treatment without bone marrow depression and exacerbating bleeding diathesis. CONCLUSION: Arsenic trioxide can be used effectively to treat APL patients by inducing apoptosis and partial differentiation in tumor cells. The precise cellular and molecular mechanisms of its therapeutic effects remain to be determined.

Treatment of Acute Promyelocytic Leukemia (APL) by a Combination of All-Trans Retinoic Acid (ATRA) and Chemotherapy / 대한혈액학회지

BACKGROUND: All-trans-retinoic acid (ATRA) induces complete remission (CR) in the great majority of patients with PML/RAR -positive acute promyelocytic leukemia (APL). However, it is associated with a rapid rise in leukocytes in one third to half the patients, with potentially fatal "ATRA syndrome". Furthermore, most of the patients relapse with maintenance therapy using ATRA alone or low-dose chemotherapy. In this study, we have analyzed the outcome for APL patients who were treated with ATRA alone or combined with low-dose chemotherapy followed by postremission chemotherapy in Chonnam University Hospital from April 1993 to December 1997. METHODS: Sixteen patients with newly diagnosed APL were eligible to analysis. Patients received 45mg/m2 ATRA until CR occurred. If initial WBC were above 5,000/microliter, low-dose chemotherapy was concomitantly given, and if during the ATRA therapy WBC were above 5,000/microliter by day 5 or 10,000/microliter by day 10, or 15,000/microliter by day 15, low-dose chemotherapy was added. Four polychemotherapy cycles or allogeneic bone marrow transplantation were given as postremission therapy. RESULTS: Median age was 34 years (range, 17 to 67). Of 16 APL patients, 15 (93.8%) achieved CR and 1 (6.2%) died of intracerebral hemorrhage. After a median follow-up of 11.5 months (range, 0 to 47), the Kaplan-Meier estimated overall survival (OS) rate was 87.1 +/- 8.6% at 3 year, the event-free survival (EFS) rate was 87.1 +/- 8.6%, 58.0 +/- 24.4% and 29.0 +/- 23.9% at 1 year, 2 year and 3 year, and the disease-free survival (DFS) rate was 92.9 +/- 6.9%, 69.6 +/- 20.7% and 46.4 +/- 23.5% at 1 year, 2 year and 3 year, respectively. CONCLUSION: The present study suggests that ATRA with or without low-dose chemotherapy followed by postremission chemotherapy is a well-tolerated and effective regimen that is shown to improve the CR rate, reduce a early mortality rate and considerably prolong the overall survival in patients with newly diagnosed APL.