br Disclosures br Acknowledgments This study was supported b
Acknowledgments This study was supported by the Austrian National Science Fund (FWF), Grant # SFB-F4704.
Introduction Acute lymphoblastic leukemia (ALL) is the most frequent childhood malignancy. Extramedullary involvement of the kidneys is seen in around 7% when assessed by intravenous pyelography and defined as nephromegaly. When present it seems associated to high white blood cell count . Kidney enlargement has no prognostic value and radiologic examination is not preformed routinely. Interestingly, kidney enlargement is usually not associated with renal function . Acute renal failure (ARF) has a large variety of etiologies but when associated to ALL it is typically due to treatment-induced tumor lysis syndrome. Within the first days after start of chemotherapy biochemical signs of tumor lysis (increase in uric acid, potassium, phosphate, creatinine and blood urea nitrogen, and a decline in calcium) are often present but clinical tumor lysis syndrome is uncommon . Pretreatment spontaneous tumor lysis syndrome is rare in ALL.
Case report A 10-year-old previously healthy Caucasian boy presented with blurred vision, headache, nausea, and vomiting. The symptoms occurred intermittently without circadian variability. The patient had bilateral papilledema. He was pale but otherwise unaffected without enlarged lymph nodes or abdominal organs by palpation. Urinary production was normal. The blood pressure was elevated: 128/91mmHg. Creatinine 101μmol/l, urea 6.7mmol/l, hemoglobin 9.5g/l, platelets 150×109/l, white blood cell count 4.5×109cells/l, absolute neutrophil count 1.75×109cells/l, and lactate dehydrogenase 645IU/l. Uric PI3K Akt mTOR Compound Library was 0.97mmol/l and rasburicase was administrated twice, resulting in a rapid decrease (Fig. 1). Urine analysis showed marginal proteinuria of 0.2g/day. An MRI scan of the cerebrum performed on day 3 showed no signs of malignancies or increased intracranial pressure. The renal failure progressed reaching a peak creatinine level of 534μmol/l. An ultrasound of the kidneys and urinary tract showed no signs of obstruction but bilateral diffuse enlargement of the kidneys (16cm in craniocaudal length on both sides). A renal biopsy and a bone marrow aspiration and biopsy were performed on the fourth day from admission. The kidney biopsy showed massive infiltration of immature lymphoblasts (Fig. 2). The bone marrow biopsy showed 90% blasts of T-cell linage (CD3+, CD4+, CD10+, CD117+, CD7+, CD5+, and CD8−). Lumbar puncture showed CNS involvement with 12×106cells/l; most of the cells were lymphoblasts. Treatment was initiated according to the NOPHO-ALL 2008 high-risk protocol. Due to high risk of tumor lysis, treatment was started with low-dose prednisolone alone (Fig. 1). Kidney function improved rapidly following initiation of therapy and dialysis did not become necessary.
Discussion In a few case reports it is evident that ARF was due to leukemic infiltration. Escobar et al. reported a 6-year-old girl who presented with uremia, slightly elevated lactate dehydrogenase, uric acid level of 11.5mg/dl (0.68mmol/l) . The peripheral blood count was normal. The most likely diagnosis was thought to be dehydration and thereby the true diagnosis of T-ALL was delayed. MRI showed massive renal enlargement. Sato et al. reported a 5-year-old boy who presented with facial edema and oliguria . He needed hemodialysis despite normal uric acid level of 5.4mg/dl (0.32mmol/l). Bone morrow aspiration later revealed the diagnosis of ALL. Like our patient, both cases had massively enlarged kidneys with severe lymphoblast infiltration. As seen in Fig. 1, administration of prednisolone was in our patients followed by a prompt decrease in creatinine, which must be due to rapid decrease in leukemic infiltration. This is also reflected in the second increase in uric acid level. In a study by Hann et al., the six patients (7%) with a renal size over two standard deviations all had white blood cell counts over 20×109cells/l . Interestingly, our patient, as well as the two other cases, had very large kidneys and uremia but normal white blood cell count. The prognostic effect of kidney enlargement at diagnosis of ALL is controversial. However, in children treated with intensive protocols renal failure at diagnosis seems unrelated to prognosis .