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Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Acute Promyelocytic Leukemia

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The basis for current treatment programs for APL is the sensitivity of leukemia cells from patients with APL to the differentiation-inducing effects of ATRA. The dramatic efficacy of ATRA against APL results from the ability of pharmacologic doses of ATRA to overcome the repression of signaling caused by the PML/RARA fusion protein at physiologic ATRA concentrations. Restoration of signaling leads to differentiation of APL cells and then to postmaturation apoptosis.[23] Most patients with APL achieve a complete remission (CR) when treated with ATRA, though single-agent ATRA is generally not curative.[24,25] A series of randomized clinical trials has defined the benefit of combining ATRA with chemotherapy during induction therapy and also the utility of using ATRA as maintenance therapy.[26,27,28] ATRA is also commonly used as a component of postinduction consolidation therapy, with treatment regimens that include several additional courses of ATRA given with an anthracycline with or without cytarabine.[10,13,14,29] Evidence for the benefit of giving ATRA with consolidation chemotherapy is derived from historical comparisons of results from adult APL clinical trials showing significant improvements in outcome for patients receiving ATRA given in conjunction with chemotherapy compared with chemotherapy alone.[13,14] For children with APL, survival rates exceeding 80% are now achievable using treatment programs that prescribe the rapid initiation of ATRA and appropriate supportive care measures.[1,8,9,10,13,14,29]

The standard approach to treating children with APL builds upon adult clinical trial results and begins with induction therapy using ATRA given in combination with an anthracycline administered with or without cytarabine. One regimen uses ATRA in conjunction with standard-dose cytarabine and daunorubicin,[8,30] while another utilizes idarubicin and ATRA without cytarabine for remission induction.[9,10] Almost all children with APL treated with one of these approaches achieves CR in the absence of coagulopathy-related mortality.[9,10,29,30] Assessment of response to induction therapy in the first month of treatment using morphologic and molecular criteria may provide misleading results as delayed persistence of differentiating leukemia cells can occur in patients who will ultimately achieve CR.[1,2] Alterations in planned treatment based on these early observations are not appropriate as resistance of APL to ATRA plus anthracycline-containing regimens is extremely rare.[14,31]

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