Tumor lysis syndrome: risk factors, diagnosis, and management.

Tumor lysis syndrome (TLS) is a potentially fatal complication of induction therapy for several types of malignancies. Electrolyte derangements and even downstream complications may also occur prior to the initial presentation to a medical provider, before an oncologic diagnosis has been established. It is therefore imperative that emergency physicians be familiar with the risk factors for TLS in children as well as the criteria for diagnosis and the strategies for prevention and management. Careful evaluation of serum electrolytes, uric acid, and renal function must occur. Patients at risk for TLS and those who already exhibit laboratory or clinical evidence of TLS require close monitoring, aggressive hydration, and appropriate medical treatment.

Tumour lysis syndrome.

Tumour lysis syndrome (TLS) represents a critical oncological emergency characterized by extensive tumour cell breakdown, leading to the swift release of intracellular contents into the systemic circulation, outpacing homeostatic mechanisms. This process results in hyperuricaemia (a by-product of intracellular DNA release), hyperkalaemia, hyperphosphataemia, hypocalcaemia and the accumulation of xanthine. These electrolyte and metabolic imbalances pose a significant risk of acute kidney injury, cardiac arrhythmias, seizures, multiorgan failure and, rarely, death. While TLS can occur spontaneously, it usually arises shortly after the initiation of effective treatment, particularly in patients with a large cancer cell mass (defined as ≥500 g or ≥300 g/m2 of body surface area in children). To prevent TLS, close monitoring and hydration to improve renal perfusion and urine output and to minimize uric acid or calcium phosphate precipitation in renal tubules are essential. Intervention is based on the risk of a patient of having TLS and can include rasburicase and allopurinol. Xanthine, typically enzymatically converted to uric acid, can accumulate when xanthine oxidases, such as allopurinol, are administered during TLS management. Whether measurement of xanthine is clinically useful to optimize the use of allopurinol or rasburicase remains to be determined.

How we treat tumor lysis syndrome.

Tumor lysis syndrome (TLS) is an oncology emergency that occurs as a result of rapid tumor cell breakdown and the consequent release of massive amounts of intracellular contents, including potassium, phosphate, and uric acid, into the systemic circulation. These metabolic disturbances lead to life-threatening conditions and may cause sudden death if not treated. TLS commonly occurs following initiation of cytotoxic treatment in patients with high-grade lymphomas or acute lymphoblastic leukemia. Spontaneous cases involving both solid and hematologic tumors have also been reported. Rarely, TLS occurs following treatment with irradiation, corticosteroids, hormonal therapy, or biologic therapy. It is necessary to identify patients at risk for TLS early in order to initiate preventive measures. In the event that preventive measures fail, the clinical parameters and signs of TLS must be understood and recognized so that treatment can begin as soon as possible, as this condition is a significant cause of morbidity and mortality.

A review of tumour lysis syndrome with targeted therapies and the role of rasburicase.

WHAT IS KNOWN AND OBJECTIVE: Tumour lysis syndrome (TLS) is an oncologic emergency with potentially devastating consequences classically associated with cytotoxic chemotherapy. In recent years, molecularly targeted drugs have assumed an increasingly important role in cancer therapeutics. The possibility of TLS is often overlooked in this setting. Rasburicase, a recombinant urate oxidase, is remarkably effective in treating hyperuricemia, thought to be central to the pathogenesis of renal injury in TLS. Our objective is to review the literature on TLS especially as it pertains to targeted therapies and summarize current knowledge and provide future directions regarding the role of rasburicase in the management of TLS. METHODS: A MEDLINE search was conducted using PubMed and the keyphrase 'tumor lysis syndrome' to identify articles describing TLS with a broad range of novel anti-cancer agents. Meeting abstracts were also reviewed. Additionally, the biomedical literature was searched using the keyword 'rasburicase'. RESULTS AND DISCUSSION: Tumour lysis syndrome has been described with nearly every class of 'targeted therapy'. This is not surprising as any drug causing death of cancer cells by any mechanism may lead to TLS in the appropriate setting. Although there is a wealth of evidence suggesting that rasburicase is extremely effective in correcting hyperuricemia, prospective trials showing that it improves hard outcomes such as acute renal failure, need for dialysis and mortality are lacking. Furthermore, much lower doses and durations of therapy than approved appear to be effective in controlling hyperuricemia, potentially leading to enormous cost savings. WHAT IS NEW AND CONCLUSION: Any effective cancer therapy can lead to TLS. Physicians should consider the risk of TLS on a case-by-case basis and determine appropriate prophylaxis. The role of rasburicase continues to evolve. Randomized controlled trials evaluating clinically relevant outcomes are needed.

A case report of fatal tumor lysis syndrome after chemotherapy in a pregnant patient with Burkitt's lymphoma.

A 35-year-old Japanese woman in the 24th week of gestation with bilateral breast enlargement was referred to hospital. She was diagnosed with Burkitt's lymphoma and admitted for detailed evaluation and treatment. Early delivery and subsequent chemotherapy was chosen after considering the gestational week, her general condition and the wishes of the patient and her husband. She gave birth to a male infant by cesarean section in the 25(th) week of gestation. It had been planned to begin high-dose chemotherapy, such as CODOX-M/IVAC, on day 7 of the puerperium; however, her general condition worsened and chemotherapy was therefore begun on day 2 after the birth. Eight hours after chemotherapy (cyclophosphamide, vincristine and doxorubicin), she developed cardiac arrest due to tumor lysis syndrome. Despite medical treatment, her bleeding tendency did not improve and she died of respiratory failure with alveolar bleeding five days after chemotherapy.

[Recommendations for tumor lysis syndrome management]. / Recomendaciones para el manejo de la lisis tumoral.

The tumor lysis syndrome represents a potentially lethal complication caused by the massive release of nucleic acids, potassium and phosphate into the circulation as a result of the lysis of neoplastic cells, which are characterized by a rapid proliferation capacity and high sensitivity to drugs. This may occur spontaneously prior to the start of treatment, becoming worse after the initiation of chemotherapy. It presents a high mortality; its prevention continues being the most important therapeutic measure. The clinical picture is characterized by the existence of hydroelectrolytic metabolism disorders, in particular hyperkalemia, hyperphosphatemia and hyperuricemia and by the appearance of an acute renal lesion. Adequate therapeutic intervention involves intravenous hydration and measures to prevent or correct metabolic alterations. This article proposes guidelines to follow both in the diagnostic stage and in the treatment of this complication.

El síndrome de lisis tumoral representa una complicación potencialmente letal provocada por la liberación masiva de ácidos nucleicos, potasio y fosfato hacia la circulación como resultado de la lisis de células neoplásicas, las cuales se caracterizan por una rápida capacidad de proliferación y alta sensibilidad a fármacos. Esto puede ocurrir de forma espontánea antes del inicio del tratamiento y agravarse luego de haberse iniciado la quimioterapia. Presenta una alta mortalidad. Su prevención continúa siendo la medida terapéutica más importante. El cuadro clínico se caracteriza por la existencia de trastornos del metabolismo hidroelectrolítico, en particular, hipercalemia, hiperfosfatemia e hiperuricemia y por la aparición de una lesión renal aguda. Una adecuada intervención terapéutica implica hidratación intravenosa y medidas para prevenir o corregir las alteraciones metabólicas. En este artículo, se proponen lineamientos para seguir tanto en la etapa diagnóstica como en el tratamiento de esta complicación.

The role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the treatment with continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF).

OBJECTIVE: To examine the role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the efficacy of continuous hemodiafiltration in the treatment of TLS. DESIGN AND SETTING: Retrospective observational study in a general intensive care unit of a university hospital. PATIENTS: Four patients with hematological disorder developing TLS after the treatment of anti-tumor chemotherapy. INTERVENTIONS: Continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) was performed at the onset of TLS. Blood samples were collected daily after ICU admission, and clinical parameters and blood levels of cytokines were evaluated. MEASUREMENTS AND RESULTS: All four patients underwent induction anti-tumor chemotherapy, during which they developed hyperuricemia, hyperkalemia, and acute renal failure. Two of them also developed multiple organ failure. Serum levels of tumor necrosis factor (TNF) -alpha, interleukin-6 (IL-6), and IL-10 prior to the initiation of PMMA-CHDF were 102+/-85 pg/mL, 1097+/-546 pg/mL, and 98+/-83 pg/mL, respectively (mean +/- SD). After three days of PMMA-CHDF treatment, corresponding blood levels were 37+/-55 pg/mL, 326+/-511pg/mL, and 9+/-8 pg/mL, respectively. Thus, all cytokine levels were significantly decreased by three days of PMMA-CHDF treatment (p<0.05, paired t-test). Following three days of PMMA-CHDF treatment, blood urea nitrogen (BUN) and serum creatinine (Cre.) were significantly decreased (pre/post BUN 42.3+/-15.4/16.5+/-8.4 mg/dL, p<0.05, pre/post Cre. 2.7+/-1.2/1.2+/-0.6 mg/dL, mean +/- SD, p<0.05). Furthermore, the clinical condition of each patient was improved after the treatment of PMMA-CHDF, and all of four patients were survived. CONCLUSION: Hypercytokinemia plays a pivotal role in the pathophysiology of TLS and PMMA-CHDF may be an effective therapeutic modality for TLS patients not only as renal replacement therapy but also as a cytokine modulator.

[Tumor lysis syndrome]. / Síndrome de lisis tumoral.

Tumor lysis syndrome (SLT) is a rare and potentially fatal entity. It represents an oncological emergency. It can be diagnosed by its clinical presentation and also by laboratory results. In most cases it is presented as a complication of the chemotherapeutic treatment of oncohematological diseases with large tumor mass. Less frequently, a syndrome of spontaneous tumor lysis has been described, or secondary to the use of corticosteroids, hydroxyurea and radiotherapy. In its most severe forms it may require hospitalization in intensive care units and invasive therapeutic measures such as hemodialysis. We report four cases of SLT with unusual presentation characteristics admitted to our Medical Research Institute.

El síndrome de lisis tumoral (SLT) es una entidad poco frecuente y potencialmente fatal. Representa una emergencia oncológica. Puede diagnosticarse por su forma de presentación clínica y también por los resultados de laboratorio. En la mayoría de los casos se presenta como complicación del tratamiento quimioterapéutico de enfermedades oncohematológicas con gran masa tumoral. Con menor frecuencia se ha descrito un síndrome de lisis tumoral espontáneo, o secundario al uso de corticoides, hidroxiurea y radioterapia. En sus formas más graves puede requerir internación en unidades de terapia intensiva y medidas terapéuticas invasivas como la hemodiálisis. Comunicamos cuatro casos de SLT con características de presentación inusual internados en nuestro Instituto de Investigaciones Médicas.

A Case Report of Atezolizumab Induced Tumor Lysis Syndrome.

BACKGROUND Advanced urothelial carcinoma has been associated with poor prognosis due to high resistance to chemotherapy and radiation until immunotherapeutic agents, such as atezolizumab, emerged as an option and have shown improved survival. However, atezolizumab is associated with side effects, which were mainly autoimmune. In this case study, we report on a rare case of atezolizumab-induced tumor lysis syndrome. CASE REPORT A 67-year-old female with a primary diagnosis of metastatic urothelial carcinoma who presented to the emergency department with generalized weakness associated with nausea and vomiting 8 days after her first cycle of atezolizumab. Laboratory values showed hyperphosphatemia, hyperuricemia, hypocalcemia, and acute kidney injury consistent with tumor lysis syndrome. CONCLUSIONS In our report, we highlight tumor lysis syndrome as a potential reaction to atezolizumab; a condition that requires prophylaxis and close laboratory monitoring.

Tumour lysis syndrome. / Síndrome de lisis tumoral.

Tumour lysis syndrome (TLS) is a life-threatening emergency characterised by a massive cytolysis with the release of intracellular electrolytes, nucleic acids, and metabolites into the circulation. TLS comprises laboratory derangements (hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia) responsible for acute kidney injury. In patients with hematologic malignancies after cytotoxic therapy or spontaneously and also in advanced solid tumours. Assessment of disease specific risk level for TLS in patients receiving anti-tumoural therapy is essential for early diagnosis. Prophylaxis is the mainstay of management of TLS. It is important to routinely initiate a risk-adapted prophylactic strategy to correct metabolic alterations and preserve renal function. High and intermediate risk patients and patients with established TLS should be managed with multidisciplinary medical care in a hospital unit to receive monitoring and medical care. Renal replacement therapy should be considered in patients with refractory TLS.

Opioid toxicity with underlying tumour lysis syndrome in a patient with CMML: a diagnostic and therapeutic challenge.

Use of strong opioids like morphine as analgesics for painful conditions in haematological malignancies is a challenging task. We report a unique case of chronic myelomonocytic leukaemia presenting with opioid toxicity overlapping with tumour lysis syndrome. The patient was on hydroxyurea-based chemotherapy for the primary disease. She was receiving oral morphine for abdominal pain due to splenomegaly. She was brought to the emergency in unresponsive state with pinpoint pupils. Opioid overdose leading to unconsciousness was suspected as the first diagnosis. Further workup revealed a final diagnosis of tumour lysis syndrome overlapping with opioid overdose. The patient was ventilated and started on naloxone infusion, and supportive measures for managing tumour lysis were added. The patient gradually improved and was extubated on the fifth day of ventilation. This case presents several learning points for the treating physician. Haematological malignancies have a dynamic course of disease with waxing and waning tumour burden during the course of chemotherapy. This fact should be kept in mind when prescribing strong opioids like morphine on outpatient basis to these patients. Massive tumour cell lysis during the course of chemotherapy may precipitate tumour lysis syndrome and may lead to renal dysfunction which makes the patient susceptible to morphine-related adverse effects. Pain physician should keep a watch for therapy-related adverse effects to avoid diagnostic and therapeutic dilemma associated with coexisting features of these two fatal conditions.

Avoiding dialysis in tumour lysis syndrome: is urate oxidase effective? - a case report and review of literature.

INTRODUCTION: Hyperuricaemia in tumour lysis syndrome (TLS) can cause acute renal failure (ARF), necessitating dialysis. Recombinant urate oxidase (rasburicase) converts uric acid to soluble allantoin, which is excreted easily. CASE REPORT: An 8-year-old boy with stage 3 Burkitt's lymphoma, TLS was successfully treated with hyper-hydration, diuretics and rasburicase, without dialysis. This is the first paediatric case in Kandang Kerbau Women's & Children's Hospital (KKH) in which rasburicase was used. We review the literature on the effectiveness of urate oxidase in avoiding dialysis in TLS. TREATMENT AND OUTCOME: Our patient developed rapidly rising serum uric acid (SUA) and progressive renal impairment. Hyper-hydration and rasburicase (0.2mg/kg) were administered. SUA rapidly decreased from 1308 to 437 mmol/L within 12 hours. Urate oxidase has shown better results than allopurinol. There was a need for dialysis in 0.4% to 1.7% of patients with haematological malignancies given rasburicase, compared to 20% in patients given allopurinol. CONCLUSIONS: Rasburicase can reverse renal insufficiency. Though expensive, it may be cost-effective by lowering incidence of dialysis, shortening the duration of intensive care and hospitalisation, allowing early chemotherapy.

Post-cytokine-release Salt Wasting as Inverse Tumor Lysis Syndrome in a Non-cerebral Natural Killer-cell Neoplasm.

The pathogenesis of cerebral/renal salt-wasting syndrome remains unknown. We herein present a case of salt-wasting syndrome with a natural killer-cell neoplasm without cerebral invasion. A 78-year-old man with hemophagocytic syndrome received two cycles of chemotherapy that did not induce tumor lysis syndrome, but repeatedly caused polyuria and natriuresis. The expression of tumor necrosis factor-α in the neoplasm led us to hypothesize that an oncolysis-induced cytokine storm may have caused renal tubular damage and salt wasting. Our theory may explain the pathogenic mechanism of cerebral/renal salt-wasting syndrome associated with other entities, including cerebral disorders, owing to the elevation of cytokine levels after subarachnoid hemorrhage.