A 56-year-old woman with a history of insulin-dependent diabetes mellitus and hypertension presented with four days of progressive fatigue, lightheadedness, cough, bleeding gums, and night sweats.
She was afebrile and had otherwise unremarkable vital signs except for a blood pressure of 104/52 mm Hg. The patient appeared ill, but was alert and oriented without gross neurological deficits. Oral exam revealed bleeding gingiva. Her lungs were clear throughout with no increased work of breathing. The remainder of her physical exam was unremarkable.
Labs were ordered and notable for a white blood cell count of 52.1 x 109 L with 65% blasts, hemoglobin of 12.4 g/dL, platelets of 23,000 x 109/L, sodium of 130 mmol/L, potassium of 5.0 mmol/L, glucose of 597 mg/dL without an anion gap, BUN of 46 mg/dL, and creatinine of 2.6 mg/dL. Additional workup was then ordered and notable for an INR of 1.8, uric acid of 10.6 mg/dl, fibrinogen of 94 mg/dl, phosphorus of 3.8 mg/dl, and ionized calcium of 1.04 mmol/L. Chest x-ray showed low lung volumes without a focal consolidation. She was started on IV crystalloids.
A bone marrow aspirate is shown. What is the diagnosis? How should this patient be managed?
Find the diagnosis and case discussion on p. 16.
Diagnosis: Acute Myeloid Leukemia with Tumor Lysis Syndrome
Acute myeloid leukemia (AML) includes a group of blood cell cancers that arise from myeloid precursor cells. Clonal expansion of these cells then suppresses normal bone marrow activity. Although rare overall, AML is the most common acute leukemia in adults, accounting for one percent of all cancer deaths in the United States. (Cancer Causes Control 2008;14:379.)
Patients with AML generally present with symptoms related to bone marrow suppression and the resultant pancytopenia—weakness and fatigability, susceptibility to infections, menorrhagia, and easy bleeding and bruising. (Obstet Gyencol 2016;128:357.) Physical exam findings may include pallor, bruising, petechiae, and hepatosplenomegaly. Lymphadenopathy is uncommon. (Cancer 2005;104:788.)
Bone marrow aspirate and biopsy confirm the diagnosis of AML. Suspicion should be raised in any patient presenting with one of the following: 20 percent or more blast cells (immature myeloid cells) in peripheral blood, unexplained cytopenias, symptoms related to cytopenias, or unexplained metabolic/oncologic emergencies such as tumor lysis syndrome and hyperleukocytosis. Acute promyelocytic anemia (APML), a subtype of AML, often presents with disseminated intravascular coagulation (DIC) as seen with this patient. (N Engl J Med 2015;373:1136.)
Treatment for AML consists of induction chemotherapy with a goal of complete remission. Induction therapy generally includes cytarabine and anthracycline treatment. AML is cured in 35-40 percent of adult patients under age 60 and in five to 15 percent of patients over 60. (Blood 2010;115:453.)
A common complication of AML is tumor lysis syndrome (TLS). It most frequently occurs in the first days after the initiation of chemotherapy, although it can also occur spontaneously in hematologic malignancies and solid tumors with high proliferative rates. TLS is characterized by the release of intracellular contents from tumor cells that overwhelm homeostasis and result in hyperkalemia, hyperuricemia, hyperphosphatemia, and corresponding hypocalcemia. This can produce uric acid or calcium phosphate crystals that damage renal tubules, leading to renal failure. Electrolyte derangements may cause seizures and life-threatening dysrhythmias.
Laboratory studies for TLS should include serum potassium, phosphorous, calcium, and uric acid. The Cairo-Bishop diagnostic criteria require at least two of these laboratory values to be abnormal or to have a change of greater than 25 percent over three days. A blood urea nitrogen (BUN) and creatinine should also be sent to assess renal function. (J Clin Oncol 2008;26:2767.)
The mainstays of TLS treatment are renal protection via aggressive fluid administration and diuresis (increase renal blood flow and glomerular filtration); reducing serum uric acid; and treating life-threatening electrolyte abnormalities. Hydration via intravenous crystalloids should target a urine output of 2 ml/kg per hour. Furosemide can also be added to increase urine output in patients who are not volume-depleted.
Reduction of serum uric acid is accomplished by administering intravenous allopurinol to block protein catabolism or by converting uric acid to a soluble byproduct using recombinant urate oxidase (rasburicase). (J Clin Oncol 2008;26:2767.) Urine alkalinization with sodium bicarbonate or acetazolamide is no longer recommended. Renal failure and hyperkalemia will require hemodialysis in some cases. (N Engl J Med 2011;364:1844.)
The patient was admitted to the medical intensive care unit with hematology/oncology consultation. A bone marrow biopsy was consistent with acute promyelocytic leukemia (APML). She began chemotherapy and her uric acid level normalized with rasburicase treatment. Her hospital course was complicated by hospital-acquired infections, severe mucositis, and renal failure requiring continuous renal replacement therapy (CRRT).
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