Tumor lysis-like syndrome in a child during treatment for visceral leishmaniasis

Abstract

A 2.5-year-old girl was admitted due to splenomegaly and pancytopenia. Laboratory analysis revealed pancytopenia and hypergammaglobulinemia, and due to the absence of fever and the relevant clinical and hematological presentation the child was initially suspected for acute lymphoblastic leukemia. Bone marrow aspiration displayed macrophages and extracellular space containing Leishmania amastigotes. Visceral leishmaniasis diagnosis due to Leishmania infantum was confirmed by the presence of high titers of Leishmania antibodies and by PCR. The patient was successfully treated with liposomal amphotericin B but during the third post-treatment day significant increases in the levels of serum uric acid, blood urea nitrogen, and phosphate were registered. The child was successfully treated with hydration and urine alkalization and resulted in full recovery of the metabolic abnormalities.

Introduction

Visceral leishmaniasis (VL) (Kala-azar) is a vector-borne tropical infection that is considered to be a disease mostly presented in poor countries within Asia, Africa, and Latin America. Nevertheless, leishmaniasis is also endemic in Mediterranean countries. ¹ The typical presentation of VL includes fever, splenomegaly, pancytopenia, and hypergammaglobulinemia. The increase in the number of immunocompromised patients like those infected with human immunodeficiency virus (HIV) has resulted in an incidence increase.^1,2 VL can affect immunocompetent hosts with genetic susceptibility to the disease as well.^4–6 We report a case of a 2.5-year-old child treated with liposomal amphotericin B (L-AMB), who developed parasite lysis syndrome successfully managed with hydration and urine alkalization.

Case presentation

A 2.5-year-old not-native healthy child with no history of travelling abroad presented with epistaxis, splenomegaly, anorexia, fatigue, and pallor. Parents referred that the child was afebrile in the last 3 months. Laboratory studies revealed anemia (Hb, 7.3 g/dl), normal white blood cell (WBC) count (WBC, 5040/μL) with lymphocytosis (lymphocytes, 76.8%), thrombocytopenia (PLT, 92,000/μL), elevated erythrocyte sedimentation rate (52 mm/h), and marked hypergammaglobulinemia (IgG, 5.76 g/dl). HIV, hepatitis B and C serology, and direct Coombs test were negative. Exams for anemia were negative. Due to the high suspicion of an underlying hematological disorder, the patient underwent a bone marrow aspirate. Bone marrow aspirate smears revealed the presence of macrophages and extracellular space containing a high number of Leishmania amastigotes mostly within the reticulo-endothelial macrophages (Figure 1). Diagnosis of VL was confirmed by the presence of high titers of anti-leishmania antibodies (IgG >1:160 by ELISA) and the parasite typed as L. Infantum by PCR. Treatment with liposomal amphotericin B (3 mg/kg/day, days 1–5, 14, and 21) was started immediately. During the third treatment day, an increase in the levels of serum uric acid (6.4 mg/dl), blood urea nitrogen (BUN) (64 mg/dl), and phosphate (6.13 mg/dl) were registered. Serum levels of calcium, potassium, and magnesium were not altered significantly compared to baseline. Due to the laboratory evidence of a tumor-like lysis syndrome (TLS) the patient underwent treatment with aggressive intravenous fluid administration, urine alkalization with bicarbonates but without allopurinol administration. On day 5, a significant improvement was achieved in the patient’s metabolic profile and laboratory values of BUN returned to normal ranges. Six months later the patient remains in excellent clinical condition and has a normal renal function.

Figure 1.

Destroyed macrophage that deliberates parasites.

Discussion

VL is a vector-borne disease caused by the parasite of the genus Leishmania and the disease is transmitted by the female sand-fly, belonging to the genera Phlebotomus. ¹ Other infrequent ways of transmission of the disease are infected blood transfusions, congenital infection, and parenteral transmission. VL causes a systemic disease characterized typically by fever, splenomegaly, and pancytopenia and may be fatal if untreated.^1–3 Greece and other Mediterranean countries are considered to be endemic for both visceral and cutaneous form of the disease. L. infantum is the most frequent species for VL although sporadic cases caused by L. tropica have been diagnosed in Greece. ⁷

TLS is characterized by a group of metabolic derangements caused by the massive and abrupt release of cellular components into the blood following the rapid lysis of malignant cells. ⁸ TLS represents the most common disease-related emergency encountered by physicians caring for children or adults with hematologic cancers and solid tumors after the initiation of aggressive chemotherapy and leads to the characteristic findings of hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. ⁸ The key to the management of TLS includes awareness of its causes, identification of high-risk patients, implementation of prophylactic measures, and monitoring of electrolyte levels. ⁸

The parasites lysis syndrome after initiation of treatment for VL could lead to a massive death of parasites and to the release of intracellular contents (potassium, phosphorus, and nucleic acids). ⁹ Although few cases of parasites lysis syndrome after initiation of treatment for VL in adults have been reported in the literature, this is to our knowledge the first case in a pediatric patient. Liberopoulos et al. reported the first case of TLS in a 41-year-old woman who developed acute renal impairment after treatment for VL and was successfully treated with fluids administration, urine alkalization, and allopurinol. ⁹ Georgiadou et al. evaluated retrospectively the rate of renal dysfunction during treatment with L-AMB in nine consecutive patients with VL and reported that five patients (56%) experienced transient deterioration of renal function that were restored to normal levels after completion of therapy. ¹⁰ In a prospective study by Liberopoulos et al., 10 consecutive adult patients with VL who were administered L-AMB showed that at the fourth treatment day levels of serum creatinine increased by 23%, BUN by 60%, and serum uric acid by 38%. The authors concluded that nephrotoxicity may be mostly related to the parasites massive death after initiation of treatment than to L-AMB nephrotoxicity. ¹¹

We conclude that the development of a parasite lysis syndrome should be considered during treatment for VL in both children and adults, especially those with high parasites loads. Awareness and prompt initiation of supportive care with fluids administration, urine alkalization, and allopurinol can prevent the development of renal complications.