Management Of Tumor Lysis Syndrome Research Articles

Emergencies in Hematology and Oncology

Clinicians must be able to recognize and treat emergencies associated with malignancies and cancer treatment. Such emergencies include metabolic, neurologic, cardiovascular, hematologic, and infectious emergencies. This review details the pathophysiology, stabilization and assessment, diagnosis and treatment and disposition and outcomes for these emergencies in hematology and oncology. Figures show mechanisms of spinal cord compression, a magnetic resonance image showing a metastasis to the thoracic spine compressing the spinal cord, a contrast-enhanced magnetic resonance image of a 54-year-old female with metastatic ovarian cancer, an electrocardiogram and a cardiac echocardiogram of a 50-year-old female with malignant pericardial effusion with cardiac tamponade, a computed tomography scan of a mass compressing the superior vena cava, a blood smear from a patient with acute myeloid leukemia, and an algorithm showing the initial management of fever and neutropenia. Tables list the management of hypercalcemia of malignancy; Cairo-Bishop definition of laboratory and clinical tumor lysis; grading, risk stratification, and management of tumor lysis syndrome; management of intracranial hypertension and seizures in adults; factors favoring low risk of severe infection in patients with neutropenic fever; Multinational Association for Supportive Care in Cancer (MASCC) risk index score; and indications for the addition of a gram-positive antibiotic to the initial empirical regimen. This review contains 8 highly rendered figures, 9 tables, and 136 references.

Medical management of tumor lysis syndrome, postprocedural pain, and venous thromboembolism following interventional radiology procedures.

The rapid expansion of minimally invasive image-guided procedures has led to their extensive use in the interdisciplinary management of patients with vascular, hepatobiliary, genitourinary, and oncologic diseases. Given the increased availability and breadth of these procedures, it is important for physicians to be aware of common complications and their management. In this article, the authors describe management of select common complications from interventional radiology procedures including tumor lysis syndrome, acute on chronic postprocedural pain, and venous thromboembolism. These complications are discussed in detail and their medical management is outlined according to generally accepted practice and evidence from the literature.

A focused review of the pathogenesis, diagnosis, and management of tumor lysis syndrome for the interventional radiologist.

The tumor lysis syndrome (TLS) is one of the most frequently encountered and dangerous oncologic emergencies.1 TLS describes a constellation of laboratory and clinical findings resulting from the rapid breakdown of tumor cells releasing their intracellular contents into the systemic circulation. It occurs most commonly in hematologic malignancies at the start of antineoplastic therapy, but has also been reported in a broad variety of solid organ malignancies, as well as occurring spontaneously without chemotherapy.2 3 4 5 As a potentially fatal oncologic emergency, it is imperative to identify patients at risk for early preventative therapy, understand the pathophysiology and consequences of this syndrome, and recognize the clinical and laboratory manifestations of TLS to ensure timely and appropriate treatment.

Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology.

Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology.

Management of tumor lysis syndrome in patients with multiple myeloma during bortezomib treatment.

Tumor lysis syndrome (TLS) is a severe, life-threatening complication that typically occurs in highly proliferative malignancies. Although TLS is unusual in multiple myeloma (MM), it is still associated with significant morbidity. Bortezomib has been widely used for the treatment of MM with encouraging results, but TLS seems to occur more frequently in patients with MM receiving bortezomib than in patients receiving other conventional agents. The purpose of this article is to present and examine several significant risk factors for the development of TLS, based on the results of a study involving patients with MM who developed TLS during bortezomib treatment. Patients with MM were treated with bortezomib-containing regimens. The early identification and intervention of high-risk patients with MM is imperative. Timely and efficient management could decrease TLS incidence rates and improve the efficacy of treatment outcomes.

Effective Prevention and Management of Tumor Lysis Syndrome in Children With Cancer: The Important Contributions of Pediatric Oncology Nurses.

The practice guidelines aimed to identify appropriate nursing management for the prevention and treatment of tumor lysis syndrome, in line with the current evidence-based medical guidelines. Using a systematic approach, 15 relevant articles were identified for the review. The evaluation of patient risk factors for tumor lysis syndrome and the appropriate medical and nursing assessment were identified. The treatment algorithms for the prevention of tumor lysis syndrome from both the medical and nursing perspectives have been established. In particular, the guidelines highlight the importance of pediatric oncology nurses in contributing to the prevention and management of tumor lysis syndrome.

Single dose rasburicase in the management of tumor lysis syndrome in childhood acute lymphoblastic leukemia: A case series.

Tumor lysis syndrome (TLS) occurs in malignancies with high proliferative potential and tumor burden, such as lymphomas and leukemias. TLS syndrome is an oncologic emergency, requiring prompt intervention. The metabolic derangements cause acute kidney failure and may lead to cardiac arrhythmias, seizures, and death. With the advent of rasburicase, a recombinant urate oxidase, there has been a decline in the TLS-mediated renal failure and the need for dialysis. The recommended regimen and doses pose a heavy financial burden for patients in developing countries like India. With data and studies proving a similar efficacy for the reduced dose and lesser number of rasburicase, we report here a case series of seven children with acute leukemias, whose TLS was managed by a single dose of rasburicase. A retrospective analysis of case records of seven children with acute lymphoblastic leukemia and TLS, admitted to our Pediatric Oncology Unit of our Hospital between the period 2011 and 2013, was done. All our patients responded to a single dose, indicating that in appropriately monitored patients, single dose followed by as-needed dosing can be cost-saving.

Rasburicase in the management of tumor lysis: an evidence-based review of its place in therapy.

Tumor lysis syndrome (TLS) is a potentially life-threatening complication of cancer therapy characterized by two or more of the following laboratory abnormalities: hyperuricemia, hyperkalemia, hypocalcemia, and hyperphosphatemia, with resultant end-organ damage, eg, renal failure, seizures, or cardiac arrhythmias. High-risk patients include those with highly proliferative cancers and/or large tumor burdens, particularly in the setting of highly effective chemotherapy, among other risk factors. Before 2002, antihyperuricemic drug therapy was limited to allopurinol, a xanthine oxidase inhibitor. Rasburicase, a recombinant urate oxidase, was approved by the US Food and Drug Administration for children in 2002 and adults in 2009, ushering in a new era in TLS therapy. We attempted to critically appraise the available evidence supporting the perceived benefits of rasburicase in the management of TLS. A Medline search yielded 98 relevant articles, including 26 retrospective and 22 prospective studies of rasburicase for the treatment of TLS, which were then evaluated to determine the best available evidence for the effectiveness of rasburicase in terms of disease-oriented, patient-oriented, and economic outcomes. Rasburicase is now a standard of care for patients at high risk of TLS despite continuing debate on the correlation between its profound and rapid lowering of plasma uric acid levels with hard patient outcomes, eg, need for renal replacement therapy and mortality. Rasburicase is dramatically effective in lowering plasma uric acid levels. The mortality and cost-effectiveness benefits of this expensive drug remain to be conclusively proven, and well designed, randomized controlled trials are needed to answer these fundamentally important questions.

Tumor lysis syndrome following sorafenib treatment in hepatocellular carcinoma

Sorafenib is indicated for the treatment of advanced hepatocellular carcinoma (HCC), but although rare, tumor lysis syndrome (TLS) can be fatal in HCC patients with a large tumor burden. The authors describe the case of a 55-year-old hepatitis B carrier who visited our clinic with progressive dyspnea for 3 weeks. Chest and abdominal computed tomography revealed a huge HCC in the left lobe of the liver with invasion of the inferior vena cava, right atrium, and pulmonary arteries. After 8 days of sorafenib administration, TLS was diagnosed based on the characteristic findings of hyperuricemia, hyperkalemia, and acute kidney injury with massive tumor necrosis by follow-up imaging. Despite discontinuation of sorafenib and supportive care, the patient’s clinical course rapidly deteriorated. The authors describe a rare but fatal complication that occurred soon after sorafenib initiation for HCC. Careful follow-up is required after commencing sorafenib therapy for the early diagnosis and management of TLS.

Restrospective Review of Incidence, Complications and Management of Tumor Lysis Syndrome in High Risk Patients with Hematologic Malignancies

Background: The tumor lysis syndrome (TLS) has been reported to be common in hematologic malignancies, particularly those associated with a high proliferative index, high tumor burden, and highly effective therapy. The classification proposed by Cairo and Bishop (Cairo MS, Bishop M. Br J Haematol 2004; 127:3-11) provides criteria that define laboratory TLS (hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia) and clinical TLS (e.g., cardiac dysrhythmias, neuromuscular irritability, signs or symptoms clearly associated with hypocalcemia, seizures, sudden death, oliguria, elevations of creatinine above baseline). Patients with laboratory manifestations of TLS are considered to be at high risk for developing clinical TLS. It has been recommended that these patients receive rasburicase as part of initial management. The purpose of this restrospective study was to survey the incidence of laboratory/clinical TLS and to attempt to evaluate the role of allopurinol vs rasburicase for TLS prophylaxis and treatment at our institution.Methods: We reviewed a series of consecutive patients presenting to our institution for initial inpatient therapy who were considered to be at high risk for tumor lysis by virtue of their hematologic diagnosis and need for aggressive chemotherapy. ICD9 codes were used to identify patients at 19 years of age or greater with Burkitt lymphoma, high tumor burden diffuse large B cell lymphoma (DLBCL)/mantle cell lymphoma (MCL), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)/lymphoma receiving their initial inpatient chemotherapy between 2007 and 2011. Electronic medical records were used to document demographic data, laboratory and clinical course information, including TLS prophylaxis/treatment strategies, from 3 days prior to 10 days post chemotherapy. Exclusion criteria were hypersensitivity to allopurinol or rasburicase or known glucose-6-phosphate dehydrogenase (G6PD) deficiency. Clinical and laboratory TLS was defined according to the method described by Cairo and Bishop.Results: A total of 149 patients met the inclusion criteria. One hundred thirty seven (92%) patients had no presenting clinical or laboratory manifestations of TLS (“prophylaxis group”) and 12 (8%) patients with manifestations of TLS at presentation were considered as the “treatment group”. In the prophylaxis group, 128 (93%) patients received allopurinol alone, 3 (2%) received rasburicase alone and 6 (5%) received both allopurinol and rasburicase. In the treatment group, all 12 patients received both rasburicase and allopurinol. Four patients in the prophylaxis group that received allopurinol alone (4/128, 3%) eventually developed TLS which was managed successfully without the addition of rasburicase. The median total dose of rasburicase in the treatment group was 12 mg (range 6-18) and repeated doses were administered on only 3 occasions. In this group, arrhythmias due to TLS were observed in 1 (8%), acute kidney injury in 8 (67%) and hyperkalemia in 3 (25%) patients. Two patients (17%) required nephrology consult and 1 (8%) received hemodialysis. Three patients (25%) in this group died - 2 from acute respiratory distress syndrome and 1 from acute subdural hematoma with herniation and pneumonia. The highest incidence of TLS was in patients with AML, in whom 11 out of 81 (13.5%) patients developed TLS.Conclusions: The incidence of TLS was approximately 11% in this high risk patient population. This study suggests that allopurinol as monotherapy can be effective as a prophylaxis strategy against TLS in a high risk patient population receiving initial chemotherapy. With appropriate monitoring, rasburicase may be added quickly in patients who develop progressive hyperuricemia during induction chemotherapy. DisclosuresNo relevant conflicts of interest to declare.

O2-1-1 - Efficacy of Rasburicase for the Prophylaxis of Tumor Lysis Syndrome in Non-Hodgkin Lymphoma Patients

Background: Tumor lysis syndrome (TLS) is a severe complication associated with anticancer chemotherapy and may become fatal. Serum uric acid (sUA) is known to play an important role in the pathology of TLS. Rasburicase, which catalyzes the oxidation of sUA to its soluble metabolite, has often been used for the prophylaxis and management of TLS. However, the optimal dose has not yet been established.Methods: We retrospectively collected data on 23 patients with non-Hodgkin lymphoma who received rasburicase at single institution between May 2012 and December 2013 for the prophylaxis of TLS before first-line chemotherapy, and we assessed clinical background, response to the drug, and occurrence of TLS.Results: The median age of the patients was 59 years (range, 28–85 years), and 14 patients were male. With regard to patients' TLS disease risk, 2 cases were designated as low risk, 6 were designated as intermediate risk, and 6 were designated as high risk. All patients had elevated serum lactate dehydrogenase levels with a high tumor burden and/or aggressive disease. The median level of sUA was 7.8 mg/dL (range, 1.3–16.4 mg/dL) and was considered elevated in 12 patients. The mean total dose of rasburicase per body weight was 0.24 mg/kg (range, 0.10–0.66 mg/kg). Patients with low or intermediate risk disease were all well managed with only 1 day of drug administration. Among the high-risk disease patients, 6 required longer duration of administration, up to 3 days, but none of the patients developed clinical TLS.Conclusions: A reduced dose of rasburicase may be effective for prophylactic TLS treatment in Japanese lymphoma patients.

Tumor lysis syndrome – An overview and current perspective

Tumor lysis syndrome (TLS) is an oncological emergency where in spontaneous or treatment-induced cell death leads to a constellation of metabolic abnormalities that can result in potentially life threatening complications. It is characterized by hyperkalemia, hyperuricemia, hyperphosphatemia and hypocalcemia. Etiopathogenesis is related to spontaneous cell death of rapidly growing tumor or more commonly to administration of cytotoxic chemotherapy in patients with hematologic malignancies and less so with solid malignancies. The precise incidence of TLS is not known, and neither racial nor gender predilection exists. Approximately 18% of the patients who develop TLS die of its complications [1]. The cornerstone of the management of TLS includes knowledge of its causes, recognition of high-risk patients, vigilant monitoring and prompt initiation of appropriate preventive and therapeutic measures when indicated.

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Introduction: Tumor lysis syndrome (TLS) is an oncologic emergency that is caused by massive tumor cell lysis with the release of large amount of potassium, phosphate, nucleic acids. Uric acid, a catabolic product of nucleic acid precipitation in renal tubules leads to acute kidney injury. TLS occurs mostly after initiation of cytotoxic therapy in patients with high-grade lymphomas and acute leukemia. TLS can also occur spontaneously with malignancies with a high proliferative rate and a large tumor burden. There are few reported cases of spontaneous TLS with solid organ malignancy. We present a case of spontaneous TLS associated with endometrial/ovarian carcinoma. A 45 years old female presented to Upstate University Hospital with a 5 day history of lower abdominal pain and abdominal distension. Her past medical/surgical history was uneventful but had limited preventative and gynecological care. On examination, she was noted to have ascites and 12 weeks size of uterus. Her initial work up revealed leukocytosis (white blood cell count 36000/µL with 90% polymorphonuclear cells), Hyperkalemia (5.6 mmol/L), Hyperphosphatemia (11.9 mg/dl), Hyperuricemia (22 mg/dl), Hypocalcemia (Ionized calcium 0.89 mmol/L), Uremia (Blood Urea Nitrogen 94 mg/dl and Creatinine 4.2 mg/dl) and anion gap metabolic acidosis (PH 7.26, Serum bicarbonate 16 mmol/L. A 13 cm enlarged uterus, 4x3x3 cm mass over the left side of uterine fundus, left adnexal mass, grossly thickened endometrium, thickened omentum/peritoneum, bilateral pleural effusion and ascites was noted on radiological examination. Cytopathological examination from pleural and ascitic fluid and tumor marker studies revealed poorly differentiated carcinoma of gynecologic origin. She was treated with intravenous fluids, Rasburic acid, urinary alkalinization and hemodialysis for spontaneous tumor lysis syndrome. Peripheral blood flow-cytometry was negative for hematological malignancy. She was deemed unfit for cyto-reductive surgery. Palliative chemotherapy with carboplatin and Paclitaxel was initiated but she later opted for hospice care and subsequently died in hospital. Although many cases of TLS have been described after treatment of non-hematologic solid tumors; there are very few reported cases of spontaneous TLS associated with solid tumors. The identification of patients at risk for TLS and determination of the degree of the risk are the cornerstone of management of TLS. Successful management of TLS include a high index of suspicion, aggressive hydration, allopurinol, urate oxidase, urinary alkalinization and dialysis.

Abstract SY24-02: Remarkable early clinical activity with the Bcl-2 selective inhibitor ABT-199: Proving the concept.

Abstract SY24-02: Remarkable early clinical activity with the Bcl-2 selective inhibitor ABT-199: Proving the concept.

Prevention and Management of Tumor Lysis Syndrome in Adults With Malignancy

Tumor lysis syndrome (TLS), an oncologic emergency that typically occurs after the treatment of a malignancy with chemotherapy and/or radiotherapy, is the result of extreme tumor cell lysis with the release of intracellular potassium, nucleic acids, and phosphorus into the systemic circulation. Tumor lysis syndrome occurs most often after administration of cytotoxic therapy in patients with high-grade lymphomas and acute lymphoblastic leukemia, but it can also occur spontaneously in tumor types that have a high proliferative rate and/or a large tumor burden. The metabolic disturbances of TLS include hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia, and acute renal failure. The most important treatment for TLS is prevention. The mainstays of TLS prevention include aggressive hydration, control of hyperuricemia with allopurinol and rasburicase treatment, and close monitoring of electrolyte abnormalities. It is crucial for clinicians to prevent, detect, and treat TLS early to prevent life-threatening complications such as acute renal failure, cardiac dysrhythmia, and seizures. The purpose of this article is to explain the pathophysiology of TLS, identify patients at risk for TLS, and detail strategies for prevention and management of this oncologic emergency.

Effectiveness of a single fixed dose of rasburicase 3 mg in the management of tumour lysis syndrome

Effectiveness of a single fixed dose of rasburicase 3 <scp>mg</scp> in the management of tumour lysis syndrome

Quiz Page December 2012: Bilateral Kidney Enlargement and Acute Kidney Injury in a Patient With HIV Infection

Quiz Page December 2012: Bilateral Kidney Enlargement and Acute Kidney Injury in a Patient With HIV Infection

Letter to the editor

Letter to the editor Vito D’Alessandro,1 Mario Greco21Respiratory Oncology Section – Internal Medicine Department, 2Hematopoietic Stem Cell Transplantation Unit Hematology-Oncology Department, of Scientific Institute, “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo (FG), ItalyWe particularly appreciated the recent successful attempt at review of management of tumor lysis syndrome, entitled “Emerging role of rasburicase in the management of increased plasma uric acid levels in patients with hematologic malignancies”1 which reported some practical management considerations and financial implications of a complex subject. The praiseworthy aim was to give clear and easily applicable indications for clinical practice from recently published off-label treatment studies, using lower and fewer doses of rasburicase than recommended.View original paper by Kennedy and colleagues.

Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) refers to the constellation of deranged metabolic state, characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and/or azotemia, secondary to rapid breakdown of tumor cells. It is a life threatening emergency that typically follows administration of chemotherapy or may be spontaneous. Malignancies which have a large tumor burden, rapid turnover, as well as speedy breakdown following chemotherapy are susceptible. Acute lymphoblastic leukemia and non-Hodgkins lymphoma (particularly Burkitt's lymphoma) are typically predisposed. TLS is best managed by early anticipation and preventive measures than the complicated task of treating an established TLS. Vigorous intravenous hydration is the cornerstone of prevention as well as treatment. Rasburicase has revolutionized the management. It is available in India for past 1 1/2 y, although the cost is a limiting factor. Children with acute leukemia in developing countries may reach health facility late, with severe anemia and hyperleukocytosis. Exchange transfusion may have to be restored to in such patients to simultaneously correct anemia and hyperleukocytosis and enable safe administration of fluids. Dialysis may be required when the metabolic 'trash' overwhelms the renal excretion, resulting in renal failure. Chemotherapeutic drugs are often administered in a phased manner in susceptible patients, in an attempt to prevent precipitous lysis of tumor cells. Presentation and management of TLS in relevance to the pediatric emergency room is outlined.

Extracorporeal life support in the acute management of tumour lysis syndrome

A 16-month old boy presented with a severe tumour lysis syndrome (TLS) complicating induction therapy for acute myeloid leukaemia. This was further complicated by a respiratory syncytial virus infection. The failure of response to escalating treatment necessitated the use of extracorporeal life support (ECLS) during continuation of his induction chemotherapy. He was weaned from support after the resolution of the TLS and completed chemotherapy successfully. ECLS may have a role to play in the acute support of children with cardiorespiratory failure as a result of malignancy or the required treatment.