The introduction of all-
Acute promyelocytic myelogenous leukemia (APML), first reported in 1957, accounts for approximately 10%–15% of cases of acute myeloid leukemia in adults [
A 24-year-old female with a past medical history of cholecystectomy and APML presented to the hospital with a 2-day history of nausea, vomiting, and epigastric pain. Her oncologic history included induction chemotherapy with cytarabine, daunorubicin, and ATRA 1 year prior to presentation. One year after induction therapy, she had clinical relapse, and therapy was changed to arsenic trioxide at a dose of 0.15 mg/kg/day (17 mg daily), which was administered intravenously 5 days per week for an anticipated 20 dose total. On Day 11 of therapy, the patient developed the current symptoms of nausea, vomiting, and epigastric pain. Physical examination revealed tenderness in the epigastrium. With regard to laboratory data, the patient had an elevated amylase level (405 U/L; normal 30–110 U/L), an elevated aspartate aminotransferase level (43 U/L; normal 14–36 U/L), an elevated lipase level (4960 U/L; normal 6–75 U/L), and a low hemoglobin level (9.8 g/dL; normal 12.3–15.3 g/dL). Computed tomography (CT) scan of the abdomen/pelvis showed evidence of prior cholecystectomy. Right upper quadrant ultrasound revealed a normal pancreas, a common bile duct 3.5 mm without intrahepatic ductal dilation, a surgically absent gallbladder, and a normal liver. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) revealed normal pancreatic morphology with no evidence of pancreas divisum. Bile aspirate was negative for microcrystalline disease. Triglycerides, antinuclear antibodies (ANA), and IgG4 levels were negative. Arsenic therapy was held during the hospitalization. The patient responded well to intravenous fluids, pain control, and antiemetics. Her biochemical parameters normalized by hospital day 8.
One week later, arsenic therapy was reintroduced at a dose of 0.1 mg/kg/day. On day 14 of therapy, the patient developed mental status changes, respiratory distress, hypotension, and recurrent pancreatitis with elevated amylase and lipase levels. CT of the abdomen and pelvis revealed heterogeneity of the pancreas consistent with pancreatitis. The arsenic trioxide was held, and succimer was initiated as a chelating agent for suspected arsenic toxicity. Blood and urine toxicology levels of arsenic were significantly elevated 25 days after cessation of therapy. Further workup for the altered mental status included EEGs which revealed generalized slowing consistent with toxic metabolic encephalopathy. The patient eventually required a tracheostomy and a percutaneous gastrojejunostomy and was transferred to a skilled long-term care facility.
Arsenic is a naturally occurring element that is found in the earth’s crust. It has a long been used in various commercial and industrial products, pharmaceuticals, and as an agent of deliberate poisoning [
Although arsenic has long been known to act as a carcinogen in the human skin, lung, liver, kidney, and urinary bladder, arsenic trioxide (As2O3) has also been demonstrated to have anticancer activity in acute promyelocytic leukemia [
Arsenic has been suggested to be involved in cytotoxicity and genotoxicity by generation of nitric oxide and lipid peroxide [
The early clinical course of arsenic intoxication often mimics gastroenteritis. Symptoms can develop from 30 minutes to several hours following ingestion [
Arsenic-induced pancreatitis, whether secondary to intentional, accidental, or as part of chemotherapeutic therapy, is rare. An extensive review of the literature revealed 3 cases of arsenic-induced pancreatitis. In 1985, a case report describes a healthy 38-year-old female who presented with nausea, vomiting, and diarrhea 2 hours after ingesting herbal tea [
Acute pancreatitis is not commonly associated with arsenic toxicity especially when used for chemotherapeutic purposes. Although seemingly rare, it should be considered as a possible side effect and should certainly be part of the differential diagnosis of drug-induced pancreatitis. It is unclear if dose reduction of arsenic trioxide aids in the prevention of subsequent episodes of pancreatitis. It is also unclear if therapy with arsenic trioxide should be discontinued after the first episode of pancreatitis provided all other etiologies are excluded. Further studies are needed to evaluate and analyze this clinical issue.