Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than ...
Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leu-kemia/retinoic acid receptor-alpha (PML/$RAR{\alpha}$) isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.
Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leu-kemia/retinoic acid receptor-alpha (PML/$RAR{\alpha}$) isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.
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문제 정의
Treatment strategies continue to evolve rapidly, with a focus on minimizing cytotoxic chemotherapy and introducing ATO as part of initial therapy. This review will discuss the incidence, molecular pathogenesis, diagnostic and therapeutic progres, and future themeutic ferspeoives of APL in children.
가설 설정
(c) The hyperbasophilic microgranular subtype has an increased nucleocytoplasmic ratio and strongly basophilic cytoplasm with qecoplasmic budding that mimics miaomeakaryocytes. There are few granules and no Auer rods, (d) PLZF-RAR alpha (M3i) variants have regularcondensed chromatin in the nucleus. There are fewer granules, arwl Auer rods air rare compared with the hypeieranular subtype.
성능/효과
Limited studies have reponed therapeutic results using combinations of ATRA and anthracycline-based chemotherapy in children with APL”', In general, these studies showed improved outcome, with CR rates above 90% and a disease-free survival rate of 77%. These outcomes in children are comparable with those reported in adult patients.
The efficacy of ATO for the treatment of both newly dienosed and refractory or relapsed patients with APL has been proven in adults and children14, 15). These studies reported a second CR rate of80-90% and OS at 1~3 years of50-70%. ATO is administered intravenously at a recommended dose of 0.
후속연구
Despite these promising results, the current recommendation for induction therapy in newly diagnosed APL is the standard approach with ATRA+chemotherapy; It might appear reasonable to consider the possibility of a randomized study comparing conventional treatment using ATRA+chemotherapy with ATO alone or ATRA+ATO to minimize the chemotherapy in patients with good or intermediate-risk diseae.
참고문헌 (47)
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