Burkitt's lymphoma

ARDS developed in association with tumor lysis syndrome (TLS) in a patient with non-Hodgkin's lymphoma. Although a number of life-threatening complications have been noted to occur following TLS, this appears to be the firm report of ARDS developing in association with TLS.

(CHEST 1998,113:550-52)

Key words: acute respiratory distress syndrome; non-Hodgkin's lymphoma; tumor lysis syndrome

Abbreviation: TLS=tumor lysis syndrome

Tumor lysis syndrome (TLS) is characterized by several metabolic derangements resulting from rapid lysis of tumor cells and is seen most frequently following chemotherapy for neoplasms with a high mitotic rate. Cardiac arrhythmias and renal failure are both well described fatal complications of the syndrome.[1,2] A patient with highgrade lymphoma complicated by acute TLS developed ARDS. An extensive MEDLINE search (1966-1997) leads one to believe this is the first report of ARDS occurring in association with TLS.

Case Report

A previously healthy 26-year-old man presented with a 10-day history of abdominal pain, night sweats, and shortness of breath. A radiograph of the chest revealed bilateral pleural effusions, and cytologic analysis of the pleural fluid was consistent with lymphoma. CT scans of the chest, abdomen, and pelvis revealed massive pericardial, epiphrenic, and retroperitoneal lymphadenopathy. A staging laparotomy was performed and demonstrated ascites with multiple tumor nodules present throughout the abdominal cavity. Results of an omental biopsy confirmed the diagnosis of a high-grade lymphoma.

His immediate postoperative course was complicated by hyperpyrexia and failure to wean from the ventilator. Significant levels of positive end-expiratory pressure and a high fraction of inspired oxygen were needed to maintain adequate systemic oxygenation. A chest radiograph taken at this time revealed bilateral pulmonary infiltrates consistent with ARDS (Fig 1). Arterial blood gas value analysis, with fraction of inspired oxygen of 80%, revealed a pH value of 7.22; [Pco.sub.2], 36 mm Hg; and [Po.sub.2], 112 mm Hg. On postoperative day 1, the creatinine level had increased from 1.0 to 2.3 mg/dL (normal value, 0.6 to 1.2 mg/dL); phosphorus value, from 2.7 to 7.3 mg/dL (normal value, 2.5 to 4.5 mg/dL); and potassium level, from 4.1 to 5.2 meEq/L (normal value, 3.5 to 5.0 mEq/L). Calcium level had decreased from 9.8 to 1.2 mg/dL (normal value, 8.5 to 10.0 mg/dL) and uric acid value was markedly elevated at 28 mg/dL (normal value, 3.5 to 7.2 mg/dL), Amylase level was 130 U/L (upper limit of normal, 125 U/L). Pulmonary capillary wedge pressure was 15 mm Hg, pulmonary artery pressure was 40/24 mm Hg, cardiac output was 9.7 L/min, and calculated systemic vascular resistance was 574 dyne.s.[cm.sup.-5].

[FIGURE 1, ILLUSTRATION OMITTED]

The clinical diagnoses of TLS and ARDS were made. The TLS was treated aggressively with intravenous fluids, with alkalinization of the urine, and with allopurinol therapy. Hemodialysis was necessary to control persistent hyperkalemia, which resolved as renal function slowly improved. ARDS was managed with continued mechanical ventilation, high levels of fraction of inspired oxygen, and positive end-expiratory pressure. The patient's alveolar-arterial oxygen pressure difference and pulmonary infiltrates gradually improved; he was weaned from mechanical ventilation over a period of 48 h and was successfully extubated 9 days after TLS developed.

Discussion

Acute TLS usually is seen as a complication of chemotherapy for several hematologic and nonhematologic malignant neoplasms.[2-4] It also has been reported to occur after steroid therapy[5] and spontaneously in a patient with lymphoma and a large tumor burden.[6] Cell lysis with subsequent release of potassium, nucleic acids, and phosphates into the extracellular environment is believed to be responsible for the hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, and azotemia characteristic of this syndrome. Complications of TLS that have been reported in the medical literature include life-threatening arrhythmias from hyperkalemia,[1] acute renal failure from uric acid and xanthine nephropathy,[7,8] and seizure resulting from electrolyte abnormalities.[9] Preexisting renal failure and low urine output appear to increase the risk of complications developing with TLS.[5] Effective treatment strategies that have been reported to be useful in TLS include vigorous hydration to increase urine flow and administration of allopurinol to decrease uric acid levels.[10] Alkalinizing the urine decreases the solubility of uric acid but also has been shown to increase the risk of calcium phosphate precipitation;[11] therefore, its use in the presence of hyperphosphatemia remains controversial. Hemodialysis occasionally is needed to control life-threatening hyperkalemia, as illustrated in the case described herein.

The evolution of this patient's clinical course fulfills the clinical criteria for TLS based on the presence of hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and azotemia in the setting of a high-grade lymphoma. It is likely that surgery and manipulation of the tumor mass precipitated tumor lysis. From the review of the medical literature, the natural history and mortality of TLS are not clearly defined. However, there is a consensus that early recognition and aggressive therapy can minimize mortality. The case reported here demonstrates these aspects of TLS.

Although in this case it appears that ARDS was a direct result of TLS, the possibility that ARDS was secondary to mild pancreatitis cannot be completely excluded. However, the trivial elevation in serum amylase and the normal-appearing pancreas shown on the CT scan of the abdomen and at exploratory laparotomy make this unlikely.

The pathogenesis of ARDS in the setting of tumor lysis is unclear. it is unlikely to be related to the serum electrolyte abnormalities since these occur in other disease processes and do not result in ARDS. In this case, ARDS and hyperpyrexia occurred rapidly following the onset of tumor lysis, suggesting that they could have been due to the result of the release of cytokines or other active mediators. The use of high-dose cytokines as treatment for certain malignant neoplasms has been associated with an increase in pulmonary capillary pressure leading to the development of noncardiogenic pulmonary edema[12] and would support such a mechanism for ARDS occurring in the setting of TLS. The risk of ARDS developing in the setting of TLS may depend on the degree of cell lysis, the speed of release of mediators into the pulmonary circulation, and the susceptibility of the alveolar-capillary membrane to injury.

Conclusion

This case would indicate that ARDS can occur due to tumor lysis alone. For this reason, ARDS should be added to the differential diagnosis of respiratory failure occurring in patients with aggressive lymphoma undergoing tumor lysis.

References

[1] Arseneau JC, Bagley CM, Anderson T, et al. Hyperkalemia, a sequel to chemotherapy of Burkitt's lymphoma. Lancet 1973; 1:10-14

[2] Cohen LF, Balow JE, Magrath IT, et al. Acute tumor lysis syndrome: a review of 37 patients with Burkitt's lymphoma. Am J Med 1980; 68:486-91

[3] Hande KR, Garrow GC. Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma. Am J Med 1993; 94:133-39

[4] Trendle MC, Tefferi A. Tumor lysis syndrome after treatment of chronic lymphocytic leukemia with cladribine [letter]. N Engl J Med 1994; 330:1090

[5] Dhingra K, Newcom SR. Acute tumor lysis syndrome in non-Hodgkin's lymphoma induced by dexamethasome. Am J Hematol 1988; 29:115-16

[6] Jasek AM, Day JH. Acute spontaneous tumor lysis syndrome. Am J Hematol 1994; 47:129-31

[7] Frei E, Bentzel C, Reiselbach R, et al. Renal complications of neoplastic disease. J Chronic Dis 1963; 16:757-76

[8] Band PR, Silverberg DS, Henderson JF, et al. Xanthine nephropathy in a patient with lymphosarcoma treated with allopurinol. N Engl J Med 1970; 283:354-57

[9] Haller C, Dhadly M. The tumor lysis syndrome [letter]. Ann Intern Med 1991; 114:808-09

[10] Silverman P, Distelhorst C. Metabolic emergencies in clinical oncology. Semin Oncol 1989; 16:504-15

[11] Tsokos GC, Balow JE, Speigel RJ, et al. Renal and metabolic complications of undifferentiated and lymphoblastic lymphomas. Medicine (Baltimore) 1981; 60:218-29

[12] Saxon RR, Klein JS, Bar MH, et al. Pathogenesis of pulmonary edema during interleuldn-2 therapy: correlation of chest radiograph and clinical findings in 54 patients. Am J Radiol 1991; 156:281-85

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