Treatment
APL is unique among myeloid leukemias due to its sensitivity to all-trans retinoic acid (ATRA), a derivative 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 is typically combined with anthracycline based chemotherapy resulting in a clinical remission in approximately 90% of patients. ATRA alone is capable of inducing remission but it is short-lived in the absence of anthracycline. Arsenic trioxide (As2O3) is currently being evaluated for treatment of relapsed / refractory disease. After stable remission is induced, the standard of care is to undergo 2 years of consolidation chemotherapy with Methotrexate, Mercaptopurine, and ATRA. Nearly all patients will relapse without consolidation therapy.
ATRA therapy is associated with the unique side effect of retinoic acid 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.
Allogeneic bone marrow or stem cell transplantation are the preferred treatment options for relapsed or 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. Recent Studies suggest the the X-RARĪ± oligomerization domain as a promising target for molecular therapeutical intervention leading to an inhibition of the leukemic phenotype through degradation of the fusion protein.
Read more about this topic: Acute Promyelocytic Leukemia
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