The acute tumor lysis syndrome has been reported in patients with aggressive non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and rarely in other ...
Increasing Recognition of Corticosteroid-Induced Tumor Lysis Syndrome in Non-Hodgkin’s Lymphoma JOSEPH SPARANO, MD, MARK RAMIREZ, MD, AND PETER H. WIERNIK, MD
The acute tumor lysis syndrome has been reported in patients with aggressive non-Hodgkin’s lymphoma, acute lymphoblastic leukemia, and rarely in other malignancies in association with the administration of cytotoxic chemotherapy. We report a case of a young man with a large cell lymphoma in whom the acute tumor lysis syndrome developed in association with the administration of corticosteroids. Two similar cases have been reported recently. Clinicians who treat patients with neoplastic diseases should be aware that corticosteroids alone may produce this potentially life threatening complication. Cancer 651072-1073, 1990.
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is a well-recognized clinical entity characterized by hyperkalemia, hyperuricemia, hypocalcemia, hyperphosphatemia, lactic acidosis, and acute renal insufficiency. In addition, in some instances it is characterized by sudden death in patients with rapidly proliferating neoplastic diseases, such as high-grade non-Hodgkin’s lymphoma (Burkitt’s lymphoma and lymphoblastic lymphoma) or acute lymphocytic leukemia, who have cytotoxic chemotherapy. The syndrome is precipitated by cytotoxic chemotherapy that induces cell death and allows rapid release of intracellular substances that produce the metabolic abnormalities. Recently, we saw a case of acute tumor lysis syndrome in a patient with a high-grade non-Hodgkin’s lymphoma induced by high-dose corticosteroids. A 19-year-old man presented with a 2-month history of abdominal pain and melena. Physical examination showed a midepigastric mass that measured 15 cm from the xiphoid process, but had no peripheral adenopathy. Abdominal computed tomographic (CT) scan showed a large gastric mass that extended posteriorly into the pancreas. Endoscopic biopsy of the stomach showed infiltration of the lamina propria with large cell lymphoma. A bone marrow biopsy and aspiration and a lumbar puncture were normal. The results of liver function tests were normal with the exception of a serum lactate dehydrogenase of 356 IU/1 and an albumin of 2.7 gm/dl. The abdominal tumor was not resectable. Therefore, the patient was treated with abdominal radiotherapy and received a total dose of 1500 cGy. During a period of several HE ACUTE TUMOR LYSIS SYNDROME
From the Albert Einstein Cancer Center and Montefiore Hospital and Medical Center, Bronx, New York. Address for reprints: Joseph Sparano, MD, Department of Oncology, Montefiore Hospital, 1 1 1 East 210th Street, Bronx, NY 10467. Accepted for publication July 10, 1989.
days the following developed: a malignant left pleural effusion, abdominal distention with an increase in the size of the abdominal mass, right mental nerve paresthesia, and bilateral sustained ankle clonus. A cranial CT scan with contrast and lumbar puncture were normal. The patient then received an emergency intravenous injection of 100 mg of dexamethasone for presumed spinal cord compression. Within 12 hours routine serum electrolyte studies showed a sodium level of 125 mEq/l, a potassium level of 8.3 mEq/l, a chloride level of 87 mEq/l, a carbon dioxide level of 12 mEq/l, a blood urea nitrogen (BUN) level of 24 mg/dl, a creatinine level of 1.5 mg/dl, a glucose level of 31 1 mg/dl, a phosphorus level of 9.4 mg/dl, a calcium level of 7.8 mg/dl, and a uric acid level of 24 mg/ dl. An arterial blood gas analysis showed a pH of 7.38, 32 mm Hg of pC02, and 65 mm Hg of p02. The patient became oliguric transiently but responded to diuretics. The patient was treated appropriately with vigorous alkaline diuresis, allopurinol, and sodium polystyrene sulfonate. The BUN rose to 57 mg/dl, and the creatinine to 1.9 mg/dl, but both returned to normal within 1 week. Forty-eight hours after the administration of corticosteroids, the ankle clonus resolved and the abdominal mass was no longer palpable. A myelogram was normal, and the spinal fluid had a normal protein and glucose concentration. A concentrated specimen of spinal fluid showed no malignant cells. Characteristically, the acute tumor lysis syndrome occurs in association with the administration of cytotoxic chemotherapy in patients with Burkitt’s lymphoma, lymphoblastic lymphoma, or acute leukemia.’-3 It has also been reported in association with cytotoxic chemotherapy in patients with indolent non-Hodgkm’s lymphoma, small cell lung cancer, and medulloblastoma. The syndrome has been reported rarely in patients who received non-
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TUMORLYSISIN NON-HODKIN’S LYMPHOMA
cytotoxic therapy, such as tamoxifen for breast cancer and interferon for cutaneous T-cell l y m p h ~ m a . ~ Re.~ cently, the acute tumor lysis syndrome secondary to corticosteroids in patients with malignant lymphoma has been reported in two patient^.^,^ The first patient was a 36-year-old man with relapsed lymphoblastic lymphoma and bone marrow involvement who received 125 mg of intravenous methylprednisolone for treatment of an allergic reaction followed within 24 hours by the acute tumor lysis syndrome. This was associated with a decrease in the leukocyte count from 35 X 103/plwith 23% lymphoblasts to 1.9 X 103/pl with rare blasts.6 The second patient was a 30-year-old man who had a diffuse large cell lymphoma that produced a large scalp mass, massive retroperitoneal adenopathy, and spinal cord compression. The patient was treated with 10 mg of dexamethasone intravenously every 6 hours followed within 72 hours by oliguria and the acute tumor lysis syndrome. This was associated with a significant reduction of the scalp mass.7 Our patient represents the third reported case of tumor lysis syndrome in a patient with a high-grade non-Hodgkin’s lymphoma after treatment with corticosteroids alone. The characteristics of patients in whom acute tumor lysis syndrome secondary to corticosteroids is prone to develop are essentially identical to those characteristicsof patients in whom tumor lysis syndrome secondary to cytotoxic agents is likely to develop, namely high-grade lymphomas and bulky disease or bone marrow involve-
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ment. This seems to be associated with the use of high doses of corticosteroids. However, the second patient shows that this may also occur with moderate doses of corticosteroids, and that in this setting the onset of the syndrome may be delayed. Our report and the reports of other researcher^^,^ suggest that steroid-induced tumor lysis syndrome may occur more frequently than was believed previously. Because steroids are used commonly for various indications in the treatment of patients with neoplastic disease, physicians who treat patients with large, rapidly growing tumors should be aware of this potential complication. REFERENCES 1. Marcus SL, Einzig AI. Acute tumor lysis syndrome: Prevention and management. In: Dutcher JP, Wiernik PH, eds. Handbook of Hematologic and Oncologic Emergencies. New York: Plenum Publishing, 1987; 9-16. 2. Cohen LF, Balow JE, Magrath IT, Poplack DG, Ziegler JL. Acute tumor lysis syndrome: A review of 37 patients with Burkitt’s lymphoma. Am J Med 1980; 68:486-49 1. 3. Tsokos GC,Balow JE, Spiegel RJ, Magrath IT. Renal and metabolic
complications of undifferentiated and lymphoblastic lymphomas. Medicine 1981; 60218-229. 4. Cech P, Block JB, Cone LA, Stome R. Tumor lysis syndrome after tamoxifen flare. N Engl J Med 1986; 3 15:263-264. 5. Fer MF, Bottino B, Sherwin SA. Atypical tumor lysis syndrome in a patient with T cell lymphoma treated with recombinant leukocyte interferon. Am JMed 1984; 77:953-956. 6. Smith T. Tumor lysis syndrome after steroid therapy for anaphylaxis. South Med J 1988; 81:415-416. 7. Dhingra K, Newcom S. Acute tumor lysis syndrome in non-Hodgkin lymphoma induced by dexamethasone. Am J Hematol 1988; 29: 115-1 16.
