Cardiac stunning as a manifestation of ATRA differentiation syndrome in acute promyelocytic leukemia

Abstract

Acute promyelocytic leukemia (APL) is a specific type of acute myelogenous leukemia characterized by the reciprocal translocations between the long arms of chromosomes 15 and 17 [t(15;17)] leading to the fusion of the retinoic acid receptor and the promyelocytic leukemia (PML) genes, called PML/RARalpha. The PML/RARalpha gene product acts as a transcription repressor, resulting in the blocking of the differentiation of APL blasts at the stage of promyelocytes. Pharmacological doses of all-trans retinoic acid (ATRA) reverse this blockage and induce disease remission. However, although ATRA is well tolerated in the majority of the APL patients treated with ATRA and idarubicin regimen (AIDA), approximately one quarter of them develop a complication denominated ATRA differentiation syndrome (DS), formerly known as retinoic acid syndrome [1–3]. The onset of DS ranges from 2 to 21 days (median of 10 days) after initiating ATRA therapy. The full development of DS is characterized by unexplained fever, weight gain, edema, interstitial pulmonary infiltrates with dyspnea, pleural and pericardial effusions, episodic hypotension, and acute renal failure. The most frequent manifestations are respiratory distress and fever, affecting more than 80% of DS patients. Acute myocardial ischemia is not commonly observed in DS. As far as we know, there is only one case report describing this complication [4]. Through early diagnosis, DS responds well to the administration of dexamethasone, with decrease in mortality from 30% to less than 10% in the patients suffering from it. The pathogenesis of this complication is not completely clarified, but increased expression of adhesion molecules on blasts and on endothelial cells and the release of inflammatory cytokines may be the main explanation [5].