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25 juli 2012: Als aanvulling op dit artikel, onderaan abstract van deze studie: Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy. toegevoegd. Met referentielijst.

18 oktober 2005: Bron: Ann Oncol. 2005 Oct 14;

Arsenic trioxide (Arsenicum) is uiterst effectief als eerstelijns behandeling voor APL. - Acute Promyelocytische leukemie. Resultaten van een arsenic trioxide combinatie behandeling met chemotherapie/ATRA vraagt verdere studies aldus de onderzoekers die met deze resultaten uit een fase II studie naar buiten kwamen. Deze studie is uitgevoerd bij 111 APL patiënten.

RESULTATEN: Een complete remissie werd gezien bij 95 patiënten (85.6%). Met een mediane follow-up periode van 16.5 (range 1-57) maanden, 1- en 2-jaar ziektevrije overleving was 88.3% en 63.7%, respectievelijk; 24 patiënten kregen een recidief, 19 ervan bereikten een tweede complete remissie, opnieuw met arsenic trioxide. Derde en vierde remissies werden gezien bij sommige patiënten die een nieuw recidef hadden gekregen. En opnieuw met arsenic trioxide. Voor de patiënten met complete remissies, 1- en 3-jaars overleving was 95.5% en 87.6%, respectievelijk. Minimal residual disease (MRD) was positief in vier (8.3%) van de 48 casussen gedurende 1 jaar na ingaan van remissie proces drie van hen kregen alsnog een klinisch vastgesteld recidief.

Ann Oncol. 2005 Oct 14

Treatment of acute promyelocytic leukemia with arsenic trioxide without ATRA and/or chemotherapy.

Ghavamzadeh A, Alimoghaddam K, Ghaffari SH, Rostami S, Jahani M, Hosseini R, Mossavi A, Baybordi E, Khodabadeh A, Iravani M, Bahar B, Mortazavi Y, Totonchi M, Aghdami N.

Haematology, Oncology and BMT Research Centre, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Arsenic trioxide is effective and approved for treatment of relapsed or refractory acute promyelocytic leukemia (APL) cases resistant to all-trans retinoic acid (ATRA), but its effect on new cases of APL is not clear. Materials and methods: We studied 111 patients with APL. Arsenic trioxide was infused at 0.15 mg/kg daily dose, until complete remission was achieved. Then, after 28 days of rest, arsenic trioxide was infused daily for 28 days as consolidation therapy. We studied minimal residual disease (MRD) by semi-sensitive reverse transcription polymerase chain reaction (RT-PCR) on peripheral blood samples.

RESULTS: Complete remission was observed in 95 patients (85.6%). With the median (range) follow-up period of 16.5 (1-57) months, 1- and 2-year disease-free survival was 88.3% and 63.7%, respectively; 24 patients relapsed, 19 of whom achieved a second complete remission, again by arsenic trioxide. Third and fourth remissions were seen in some relapsed patients, again by arsenic trioxide. For patients in complete remission, 1- and 3-year survival was 95.5% and 87.6%, respectively. MRD was positive in four (8.3%) out of 48 cases during 1 year after remission induction; three of them relapsed clinically.

CONCLUSIONS: Arsenic trioxide is effective as first-line treatment for APL. Results of arsenic trioxide combination therapy with chemotherapy/ATRA requires further study.

PMID: 16227315 [PubMed - as supplied by publisher]

Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy

Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy.


State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine (SJTUSM), 197, Ruijin Road II, Shanghai 200025, People's Republic of China.


To turn a disease from highly fatal to highly curable is extremely difficult, especially when the disease is a type of cancer. However, we can gain some insight into how this can be done by looking back over the 50-year history of taming acute promyelocytic leukaemia (APL). APL is the M3 type of acute myeloid leukaemia characterized by an accumulation of abnormal promyelocytes in bone marrow, a severe bleeding tendency and the presence of the chromosomal translocation t(15;17) or variants. APL was considered the most fatal type of acute leukaemia five decades ago and the treatment of APL was a nightmare for physicians. Great efforts have been made by scientists worldwide to conquer this disease. The first use of chemotherapy (CT) was unsuccessful due to lack of supportive care and cytotoxic-agent-related exacerbated coagulopathy. The first breakthrough came from the use of anthracyclines which improved the complete remission (CR) rate, though the 5-year overall survival could only be attained in a small proportion of patients. A rational and intriguing hypothesis, to induce differentiation of APL cells rather than killing them, was raised in the 1970s. Laudably, the use of all-trans retinoic acid (ATRA) in treating APL resulted in terminal differentiation of APL cells and a 90-95% CR rate of patients, turning differentiation therapy in cancer treatment from hypothesis to practice. The combination of ATRA with CT further improved the 5-year overall survival. When arsenic trioxide (ATO) was used to treat relapsed APL not only the patients but also the ancient drug were revived. ATO exerts dose-dependent dual effects on APL cells: at low concentration, ATO induces partial differentiation, while at relatively high concentration, it triggers apoptosis. Of note, both ATRA and ATO trigger catabolism of the PML-RARalpha fusion protein which is the key player in APL leukaemogenesis generated from t(15;17), targeting the RARalpha (retinoic acid receptor alpha) or promyelocytic leukaemia (PML) moieties, respectively. Hence, in treating APL both ATRA and ATO represent paradigms for molecularly targeted therapy. At molecular level, ATRA and ATO synergistically modulate multiple downstream pathways/cascades. Strikingly, a clearance of PML-RARalpha transcript in an earlier and more thorough manner, and a higher quality remission and survival in newly diagnosed APL are achieved when ATRA is combined with ATO, as compared to either monotherapy, making APL a curable disease. Thus, the story of APL can serve as a model for the development of curative approaches for disease; it suggests that molecularly synergistic targeted therapies are powerful tools in cancer, and dissection of disease pathogenesis or anatomy of the cancer genome is critical in developing molecular target-based therapies.

[PubMed - indexed for MEDLINE]


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