An unusual case of spontaneous acute tumor lysis syndrome associated with acute lymphoblastic leukemia: A case report and review of the literature

To the Editor

Tumor lysis syndrome (TLS) is a well- described potentially lethal condition that results from rapid destruction of neoplastic cells with release of cellular breakdown products into the systemic circulation [1]. It commonly occurs following therapy of malignancies such as acute leukemias and lymphomas [2]. However, acute spontaneous TLS is rare event [3]. We report a patient with acute lymphoblastic leukemia (ALL) with pericardial effusion and a mediastinal mass who developed acute spontaneous TLS prior to initiation of chemotherapy.

Case report

A 17-year-old woman was admitted to our hospital with complaints of dyspnea, fatigue, nausea and vomiting. Physical examination revealed blood pressure of 90/60 mmHg, heart rate of 120/min, respiration rate of 24/min, body temperature of 38.5°C, multiple cervical lymphadenopathy, splenomegaly 4 cm below the left costal margin. On admission complete blood count showed a white blood cell count of 18×10⁹/l consisting of 80% blasts with intensely basophilic agranular cytoplasm, the hemoglobin level of 8.2 mg/dl and the platelet count of 27×10⁹/l. Other significant labaratory values on presentation were summarized in Table I. Cardiac silhouette was enlarged on chest x-ray. 2-D transthoracic echocardiography revealed pericardial effusion and a large mediastinal mass surrounding the heart without any abnormalities in valve or ventricle functions and dimensions (Figure 1). Bone marrow aspiration demonstrated hypercellular marrow with blastic infiltration. Immunophenotypical analysis of bone marrow showed that leukemic cells were positive for CD7 (89%), CD5 (85%), CD2 (88%), CD3 (33%), CD8 (71%), HLA-DR (25%). The patient was diagnosed as mature T-ALL presenting with acute spontaneous TLS and pericardial involvement. She was in non-oliguric acute renal failure with extreme hyperuricemia. Aggresive intravenous hydration and allopurinol was initiated. On the 7th day, uricacid level decreased from 31 mg/dl to 1.3 mg/dl, urea level decreased from 130 mg/dl to to 21 mg/dl, creatinine level decreased from 2.5 mg/dl to 0.62 mg/dl, phosphorus level decreased from 11.9 mg/dl to 3.8 mg/dl. Since her biochemical parameters improved with treatment, haemodialysis was not required. Subsequently intensive chemoterapy (Hyper-CVAD program) was administered. She is still alive and in remission for 6 months.

Figure 1.  Transthoracic echocardiographic view of the heart. Minimal pericardial effusion and a large mediastinal mass surrounding the heart is seen in the apical 4-chamber view. LV: Left ventricle, RV: Right ventricle, LA: Left atrium, RA: Right atrium

Table I.  Laboratory findings of the case on admission and 7 days after admission

	Normal range	On admission	7 days after admission
Hb (gr/dl)	12–18	8.2	6
WBC (×10^9/l)	4.8–10	18	9.2
Platelet (×10^9/l)	150–450	27	33
LDH (IU/l)	240–480	21 800	–
Urea (mg/dl)	10–50	130	21
Creatinine (mg/dl)	0.5–1.2	2.5	0.62
Uric acid (mg/dl)	<7	31	1.3
Phosphorus (mg/dl)	2.7–4.5	11.9	3.8
Calcium (mg/dl)	8.4–10.2	7.3	9.1
Potassium (mmol/l)	3.5–5.5	5.2	3.8

Discussion

Acute TLS is a metabolic emergency that results from massive destruction of neoplastic cells and is characterized by hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, lactic acidosis and azotemia [4], [5]. It is usually observed as a complication of treatment of hematologic malignancies with large tumor burdens, increased sensitivity to chemotherapy and high proliferation rates [5] especially Burkitt's lymphoma [6], acute leukemia [7] and also seen in chronic lymphocytic leukemia [8], low grade lymphoma [9] and solid non- hematologic malignancies. Bulky lymphadenopathy, high white blood cell counts, elevated serum LDH, preexisting renal disease and hyperuricemia are risk factors for the development of TLS [4], [10]. However TLS is rarely observed spontaneously. Spontaneous acute TLS before treatment without any precipitating factor was reported in patients with Burkitt's leukemia/lymphoma [11], diffuse large B cell lymphoma and Richter syndrome [10], anaplastic large T cell lymphoma [12], acute myeloid leukemia [2], metastatic germ cell tumor [3], adenocarcinoma of lung [13], breast cancer [14], gastric cancer [15] and myelofibrosis [5]. Here we present a case of spontaneous acute TLS associated with ALL. To our knowledge, only two cases of severe spontaneous acute TLS with ALL were reported in the literature and none of them had acute spontaneous TLS and a large mediastinal mass and pericardial involvement together [16], [17]. Pericardial effusion and cardiac tamponade are rare and severe complications of leukemias. They may develop usually during the radiation therapy, chemotherapy, and infections in the course of the disease or rarely due to the involvement of the pericardium as a feature of perivascular infiltration [18], [19]. Our patient had pericardial effusion before initiation of any therapy and had no infection. She had a large mediastinal mass surrounding the heart detected by transthoracic echocardiography. Although not proved by histopathological studies, pericardial effusion was thought to be the result of the direct extension of ALL from the mediastinal mass.

The exact mechanism of spontaneous TLS is uncertain. Release of intracellular metabolites due to rapid tumor necrosis was suggested to play a role for development of spontaneous acute TLS [13]. Acute TLS is one of the most significant cause of acute renal failure (ARF) in cancer patients. ARF that results from acute TLS is usually oligoanuric and is multifactorial in etiology [1]. The most important cause of ARF is presipitation of uric acid in the tubulus of kidney due to hyperuricemia caused by increased turnover of nucleic acids [16]. Hyperphoshatemia contributes to renal failure by deposition of calcium phosphate complex in the renal interstitium [1], [16]. Our patient presented with non-oliguric ARF with extreme hyperuricemia and hyperphosphatemia. Diagnosis of spontaneous acute TLS that results from ALL was made as there was no contributing factor for development of renal failure.

Finally ALL presenting with acute spontaneous TLS is very rare. Since acute TLS is a medical emergency with a high mortality rate, early recognition and prevention especially in the patients at high risk for this syndrome is essential. Patients with acute TLS must be treated with aggressive intravenous hydration with saline fluids and loop diuretics to maintain adequate urine output [1], [16]. A xanthine oxidase inhibitor, allopurinol, should be added to lower plasma uric acid concentration [1], [4], [16]. Rasburicase, a new recombinant form of urate oxidase, is a safe and more effective drug than allopurinol in patients at highest risk for TLS because of its rapid onset of action, lack of need for urine alkalinization and a satisfactory safety profile [20]. Hemodialysis should be administered to control life-threatening hyperkalemia or volume overload in patients who have persistent oliguria despite aggresssive hydration [4]. Hemodialysis may be needed to remove excess uric acid in patients whom diuresis could not be maintained following adequate volume expansion [16]. Our patient was in non-oliguric ARF and was treated initially with aggresssive intravenous hydration and allopurinol. Rasburicase could not be adminestered because of unavailability of drug in Turkey. Hemodialysis was not required because there was no life-threatening hyperkalemia or volume overload and uricacid level and electrolite abnormalities were controlled with initial supportive therapy. After her renal functions and electrolytes improved, chemotherapy was initiated.

In conclusion, acute spontaneous TLS before initiation of chemotherapy in patients with ALL is extremely rare. The exact mechanisms for development of this syndrome in our patient are uncertain. Early recognition and prompt management may improve short-term outcome in patients at high risk for this syndome.