Pediatr Blood Cancer 2010;54:773–775

BRIEF REPORTSpontaneous Tumor Lysis Syndrome in a Child With T-Cell Acute

Lymphoblastic Leukemia

Daisuke Kobayashi, MD,* Marcia M. Wofford, MD, Thomas W. McLean, MD, and Jen-Jar Lin, MD, PhD

INTRODUCTION

Tumor lysis syndrome (TLS) is a metabolic derangement

resulting from the massive and rapid release of cellular components

into the blood after the lysis of tumor cells, typically hematologic

malignancies. Clinically, it manifests as hyperuricemia, hyper-

kalemia, hyperphosphatemia, hypocalcemia, and acute renal failure

(ARF). It usually occurs after initiation of chemotherapy [1].

Spontaneous tumor lysis syndrome (STLS) before chemotherapy is

a rare event that occurs mostly in Burkitt lymphoma and non-

Hodgkin lymphoma [2]. Here we report a case of STLS secondary to

T-cell acute lymphoblastic leukemia (ALL) which presented with

hyperuricemia and ARF that required dialysis therapy.

CASE REPORT

A 5-year-old female with a past history of frequent urinary tract

infections and left grade 1 vesicoureteral reflux was referred to our

hospital for anemia and severe azotemia. One month prior to

admission she had vomiting, diarrhea, and fever that lasted for

3 days. In the following month, her baseline activity and appetite

gradually decreased. She was seen by her pediatrician on the day of

admission due to malaise and pallor. Serum blood urea nitrogen

(BUN) and creatinine were 102 and 5.6 mg/dl, respectively and so

she was transferred and admitted to our hospital. On admission,

blood pressure was 113/57 mmHg, heart rate 125 beats/min,

respiratory rate 23/min, and temperature of 37.88C. Significant

physical examination findings included a 2 cm� 3 cm ecchymosis

on the left patella which her father attributed to a recent injury. There

was no lymphadenopathy, hepatomegaly or splenomegaly. Labo-

ratory findings after admission are shown in Table I. The differential

of white blood cell (WBC) was neutrophils 48%, lymphocytes 48%,

monocytes 2%, basophils 1%, and metamyelocytes 1%. Peripheral

blood smear did not reveal blasts or evidence of hemolysis.

Urinalysis was significant for moderate leukocyte esterase, uric acid

crystals, and 21–30 WBCs per high power filed. Spot urine protein

to creatinine ratio was 0.77. Serology showed C3 137 mg/dl, C4

36 mg/dl, anti-nuclear antibody positive at 1:320 dilution,

and negative antineutrophil cytoplasmic antibody, lupus serology,

anti-streptolysin-O titer, and anti-glomerular basement membrane

antibodies. Chest radiograph was unremarkable. Abdominal ultra-

sound showed mild hepatosplenomegaly and bilateral large

echogenic kidneys with right pyeliectasis.

Due to oliguric ARF and electrolyte abnormalities, intermittent

hemodialysis was started shortly after admission, in addition to

alkali supplement. Urine culture demonstrated the growth of

Enterococcus faecalis that was treated with intravenous ampicillin.

Serum uric acid at day 3 of hospitalization was elevated (Table I).

Her urine output, renal function, and serum uric acid gradually

improved with hemodialysis therapy. Contrast vesiocystourethro-

gram was unremarkable. She was discharged home at day 12 of

hospitalization. BUN and serum creatinine were 8 and 1 mg/dl,

respectively, and serum uric acid was 7.5 mg/dl. Fractional

excretion of uric acid was 25%. Three days after discharge, her

serum uric acid rose to 9.5 mg/dl while serum creatinine remained at

0.93 mg/dl. WBC count was 4.1� 109/L and peripheral blood smear

was unremarkable. Allopurinol was started. At 2 weeks after

discharge, serum creatinine was 0.5 mg/dl, serum uric acid 9 mg/dl,

and WBC count 7.1� 109/L.

She was re-admitted at 17 days after discharge for fever

and abdominal pain. Physical examination was significant for

splenomegaly. Laboratory values on admission are shown in

Table I. Peripheral blood smear demonstrated 40% blasts. Bone

marrow aspiration demonstrated hypercellular marrow with

78% lymphoblasts that were positive for CD3, CD 38, CD4, CD5,

CD7, CD8 and negative for TdT. Chromosomal testing showed

46,XX,t(5;14)(q35;q32). A diagnosis of T-cell ALL was made.

Cerebrospinal fluid was negative for leukemia (1 WBC, 0 RBC, no

leukemic blasts). She was enrolled on Children’s Oncology Group

protocol AALL0434, and induction chemotherapy was initiated

with vincristine, prednisone, PEG-asparaginase, daunorubicin,

cytarabine, and methotrexate. On the eleventh day of hospitaliza-

We report a 5-year-old female who presented with unexplainedacute renal failure (ARF) and hyperuricemia and who wassubsequently diagnosed of T-cell acute lymphoblastic leukemia(ALL). Peripheral smear was initially unremarkable. She requiredhemodialysis. Two weeks later, peripheral smear showed 40% blastsand bone marrow demonstrated T-cell ALL. Our case was the fifthand the youngest case of ALL with spontaneous tumor lysissyndrome. However, in contrast to previous reports in ALL or acute

myeloid leukemia, our patient did not have blasts noted onperiphereal blood smear and her white blood cell count and serumlactate dehydrogenase level were normal on admission, a time whendialysis-dependent ARF and severe hyperuricemia were present.Occult hematologic malignancy should be considered in cases ofARF and hyperuricemia of unknown etiology even when peripheralhematologic findings are not informative. Pediatr Blood Cancer2010;54:773–775. � 2009 Wiley-Liss, Inc.

Key words: acute renal failure; hyperuricemia; spontaneous tumor lysis syndrome; T-cell ALL

� 2009 Wiley-Liss, Inc.DOI 10.1002/pbc.22384Published online 8 December 2009 in Wiley InterScience(www.interscience.wiley.com)

——————Department of Pediatrics, Wake Forest University School of Medicine,

Winston-Salem, North Carolina

Conflict of Interest: nothing to declare.

*Correspondence to: Daisuke Kobayashi, Department of Pediatrics,

Wake Forest University School of Medicine, Medical Center

Boulevard, Winston-Salem, NC 27157.

E-mail: dkobayas@wfubmc.edu

Received 21 September 2009; Accepted 26 October 2009

tion, she was discharged home with serum BUN 15 mg/dl, creatinine

0.5 mg/dl, and serum uric acid 1.1 mg/dl. She achieved remission

by day 29 of chemotherapy, and she currently remains in remission

during consolidation therapy.

DISCUSSION

Acute TLS is an oncologic emergency that can cause electrolyte

disturbances, metabolic acidosis, ARF and in fulminant cases,

seizure, arrhythmia, and death. It occurs in 63% of pediatric cases

with ALL, 11% of acute myeloid leukemia (AML), and 18% of non-

Hodgkin lymphoma. It is usually observed after initiation of

cytotoxic chemotherapy and risk factors for its development include

tumor type, tumor burden, renal function, baseline uric acid level,

and rapid cytoreduction therapy [1]. The initiation of chemotherapy

results in rapid release of intracellular ions such as phosphorus and

potassium, metabolic products of proteins, and nucleic acids into the

bloodstream [3]. Hyperuricemia results from the catabolism of

nucleic acids to hypoxanthine, xanthine, and then uric acid by the

action of xanthine oxidase [4]. Hypocalcemia occurs as a result of

hyperphosphatemia and renal deposition of calcium phosphate

crystals [5]. Deposition of uric acid, xanthine, and calcium

phosphate crystals in the renal tubules can result in ARF, especially

when there is a reduced renal perfusion or an acidic urine pH.

Treatment options include aggressive hydration, the xanthine

oxidase inhibitor allopurinol or the recombinant urate oxidase

rasburicase, and hemodialysis therapy [6].

STLS can occur prior to the initiation of chemotherapy but it is

rare, especially in the absence of other signs of malignancy such as

hyperleukocytosis or bulky adenopathy. The initial presentations of

hyperphosphatemia, hyperkalemia, metabolic acidosis, hyperuri-

cemia, and ARF and the subsequent discovery of T-cell ALL in our

patient are consistent with STLS. In a retrospective review of 1,072

adult inpatients with ARF, Hsu et al. [2] described 12 cases of STLS:

four with Burkitt lymphoma, six with non-Hodgkin lymphoma, one

with retroperitoneal leiomyosarcoma, and one with B-cell ALL.

While STLS occurred mostly in patients with Burkitt lymphoma or

non-Hodgkin lymphoma, it was also reported in acute myeloid

leukemia (AML) [7,8], myelofibrosis [9], ALL [2,10–12], meta-

static germ cell tumor [13], and solid tumors [14].

Our case was the fifth and youngest with STLS reported for ALL.

Sharma et al.[10] described a 20-year-old patient with STLS whose

ALL was diagnosed due to a bone lesion, leukocytosis, and blasts in

peripheral smear. Akoz et al. [11] reported a 17-year-old patient

with STLS whose T-cell ALL was diagnosed by blasts on initial

blood smear. Chen and Chuang [12] reported a 14-year-old male

with pneumonia whose precursor B-cell ALL was diagnosed by

blasts on peripheral smear. After admission, he developed STLS that

resolved without chemotherapy. After supportive therapy, the ALL

went into remission spontaneously. One month later, his ALL

recurred, without tumor lysis syndrome, and he achieved a second

remission with conventional chemotherapy. Hsu et al. [2] described

a 33-year-old female with B-cell ALL and STLS in their case series

but the history was not provided. In contrast to these reports as well

as reports in AML [7,8], our patient did not have blasts in blood

smear and her WBC count and serum LDH were normal at the first

admission, a time when severe azotemia, acidosis, and electrolytes

disturbances were present. The reason is not known. Potential

causes for STLS include endogenous secretion of glucocorticoid

with infection [7,12] and fever [15]. It is possible that STLS in our

patient was triggered by a febrile gastroenteritis-like illness

one month prior to the first admission. A concomitant urinary tract

infection at the first admission may have further accelerated the

process of STLS.

Several case reports in STLS have suggested that occult

malignancy should be considered in case of unexplainable acute

renal failure with hyperuricemia [10]. Our experience in this patient

further supports this suggestion. Bone marrow aspiration/biopsy,

repeated peripheral blood smears, and/or aggressive body imaging

should be considered in these patients even when peripheral

hematologic studies are unremarkable.

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Pediatr Blood Cancer DOI 10.1002/pbc

TABLE I. Laboratory Values at the First and Second Admissions

First admission

Second

admission

White blood cell count (�109/L) 5.1 (5.5–15.5)a 7.6

Hemoglobin (g/dl) 7.8 (11.5–13.5) 9.2

Platelets (�109/L) 173 (160–360) 184

Lactate dehydrogenase (U/L) 144 (200–600) 268

Bicarbonate (mEq/L) 12 (22–30) 22

Blood urea nitrogen (mg/dl) 110 (5–15) 12

Creatinine (mg/dl) 5.6 (0.4–0.9) 0.8

Phosphorus (mg/dl) 11.2 (4.0–5.5) 4.3

Potassium (mEq/L) 5.8 (3.5–5.0) 4.1

Uric acid (mg/dl) 30 (2.3–6.5)b 7.5c

Calcium (mg/dl) 9.5 (8.5–10.5) 9.7

aReference values; bObtained at day 3 of admission; cOn allopurinol

therapy

774 Kobayashi et al.

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