External Auditory Canal and Middle Ear Relapse of Acute Promyelocytic Leukemia Treated With Arsenic Trioxide

Abstract

Extramedullary involvement occurs infrequently in acute promyelocytic leukemia and is said to be more common after treatment with all-trans retinoic acid. We describe a 9-year-old girl who had an isolated external auditory canal and middle ear relapse after treatment with all-trans retinoic acid and chemotherapy. A patient with cytogenetically and molecularly confirmed acute promyelocytic leukemia developed isolated extramedullary relapse in the auditory canal and middle ear 4 years and 9 months after initial diagnosis, while in hematologic and molecular remission, successfully treated with arsenic trioxide alone.

Extremely Late Extramedullary Relapse of Acute Promyelocytic Leukemia, Case Report and Review of the Literature

“…3). A recent review of external auditory canal and middle ear relapse found 23 similar cases previously described, with most cases occurring within the first 2 years after diagnosis [17]. While the reason for extramedullary relapse is not certain, several theories exist.…”

“…Treatment of extramedullary relapse has not been thoroughly studied, but it appears that arsenic trioxide is useful not only in medullary relapse, but in extramedul-lary relapse as well. This may be due to arsenic's ability to deposit well in epidermal tissues [17].…”

Leptomeningeal Relapse of Acute Promyelocytic Leukemia

“…EMR, as in our patient, is rarely reported in patients treated for APL [ 5 , 6 ]. EMR can occur in the CNS [ 5 - 11 ], skin [ 5 , 6 , 9 , 12 ], middle ear [ 5 , 9 , 11 , 13 ], lung [ 5 ], pleura [ 14 ], sites of vascular access [ 12 ] and sites of bone marrow aspiration and biopsy [ 12 ]. However, CNS is the predominate site of EMR with an estimated risk of 0.6 to 2% [ 5 , 6 ].…”

“…The majority of reported cases were treated with intrathecal chemotherapy with or without radiation therapy [ 6 , 8 , 10 ]. ATRA, ATO and/or chemotherapy were also used to treat systemic disease when present simultaneously [ 11 , 13 , 19 - 21 ]. Unfortunately, ATRA has limited penetration to CNS and therefore, is used primarily to treat systemic disease [ 22 ].…”

Expression of AFP and STAT3 Is Involved in Arsenic Trioxide-Induced Apoptosis and Inhibition of Proliferation in AFP-Producing Gastric Cancer Cells

“…Arsenic trioxide (As 2 O 3 ) has been successfully used to treat leukemia [11]–[13] and is active in several solid tumors, including gastric cancer [14]. The mechanism of action of As 2 O 3 includes affecting the activities of Akt, JNK kinases, NF-κB, glutathione, calcium signaling, reactive oxygen species(ROS), and caspases, as well as pro- and anti-apoptotic proteins [15]–[18].…”