Initial treatment Tretinoin Mitozantrone Methotrexate<unk>  is unique among leukemias due to its sensitivity to all-trans retinoic acid (ATRA; tretinoin), the acid form of vitamin A. Treatment with ATRA dissociates the NCOR-HDACL complex from RAR and allows DNA transcription and differentiation of the immature leukemic promyelocytes into mature granulocytes by targeting the oncogenic transcription factor and its aberrant action. Unlike other chemotherapies, ATRA does not directly kill the malignant cells. ATRA induces the terminal differentiation of the leukemic promyelocytes, after which these differentiated malignant cells undergo spontaneous apoptosis on their own. ATRA alone is capable of inducing remission but it is short-lived in the absence of concurrent "traditional" chemotherapy. As of 2013 the standard of treatment for concurrent chemotherapy has become arsenic trioxide, which combined with ATRA is referred to ATRA-ATO; before 2013 the standard of treatment was anthracycline (e.g. daunorubicin, doxorubicin, idarubicin or mitoxantrone)-based chemotherapy. Both chemotherapies result in a clinical remission in approximately 90% of patients with arsenic trioxide having a more favorable side effect profile. ATRA therapy is associated with the unique side effect of differentiation syndrome. This is associated with the development of dyspnea, fever, weight gain, peripheral edema and is treated with dexamethasone. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes. The monoclonal antibody, gemtuzumab ozogamicin, has been used successfully as a treatment for<unk> , although it has been withdrawn from the US market due to concerns regarding potential toxicity of the drug and it is not currently marketed in Australia, Canada or the UK. Given in conjunction with ATRA, it produces a response in around 84% of patients with<unk> , which is comparable to the rate seen in patients treated with ATRA and anthracycline-based therapy. It produces less cardiotoxicity than anthracycline-based treatments and hence may be preferable in these patients. Maintenance therapy After stable remission was induced, the standard of care previously was to undergo 2 years of maintenance chemotherapy with methotrexate, mercaptopurine and ATRA. A significant portion of patients relapsed without consolidation therapy. In the 2000 European<unk>  study, the 2-year relapse rate for those that did not receive consolidation chemotherapy (ATRA not included) therapy was 27% compared to 11% in those that did receive consolidation therapy (p2O3) is currently being evaluated for treatment of relapsed / refractory disease. Remission with arsenic trioxide has been reported. Studies have shown arsenic reorganizes nuclear bodies and degrades the mutant PML-RAR fusion protein. Arsenic also increases caspase activity which then induces apoptosis. It does reduce the relapse rate for high risk patients. In Japan a synthetic retinoid, tamibarotene, is licensed for use as a treatment for ATRA-resistant<unk> . Investigational agents Some evidence supports the potential therapeutic utility of histone deacetylase inhibitors such as valproic acid or vorinostat in treating<unk> . According to one study, a cinnamon extract has effect on the apoptotic process in acute myeloid leukemia HL-60 cells.
Acute promyelocytic leukemia
Prolymphocytic leukemia
Acute megakaryoblastic leukemia
Myeloid leukemia
Acute monocytic leukemia
T-cell leukemia
Monocytic leukemia
Acute erythroid leukemia