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The New England Journal of Medicine May 2011
Review
Topics: Acute Kidney Injury; Child; Humans; Male; Risk Assessment; Tumor Lysis Syndrome
PubMed: 21561350
DOI: 10.1056/NEJMra0904569 -
Journal of the American Society of... Jun 2022The pathophysiology of AKI during tumor lysis syndrome (TLS) is not well understood due to the paucity of data. We aimed to decipher crystal-dependent and...
BACKGROUND
The pathophysiology of AKI during tumor lysis syndrome (TLS) is not well understood due to the paucity of data. We aimed to decipher crystal-dependent and crystal-independent mechanisms of TLS-induced AKI.
METHODS
Crystalluria, plasma cytokine levels, and extracellular histones levels were measured in two cohorts of patients with TLS. We developed a model of TLS in syngeneic mice with acute myeloid leukemia, and analyzed ultrastructural changes in kidneys and endothelial permeability using intravital confocal microscopy. In parallel, we studied the endothelial toxicity of extracellular histones RESULTS: The study provides the first evidence that previously described crystal-dependent mechanisms are insufficient to explain TLS-induced AKI. Extracellular histones that are released in huge amounts during TLS caused profound endothelial alterations in the mouse model. The mechanisms of histone-mediated damage implicates endothelial cell activation mediated by Toll-like receptor 4. Heparin inhibits extracellular histones and mitigates endothelial dysfunction during TLS.
CONCLUSION
This study sheds new light on the pathophysiology of TLS-induced AKI and suggests that extracellular histones may constitute a novel target for therapeutic intervention in TLS when endothelial dysfunction occurs.
Topics: Acute Kidney Injury; Animals; Endothelium; Histones; Humans; Kidney; Mice; Tumor Lysis Syndrome
PubMed: 35523579
DOI: 10.1681/ASN.2021070997 -
Kidney & Blood Pressure Research 2020Tumor lysis syndrome (TLS) is an oncologic emergency due to a rapid break down of malignant cells usually induced by cytotoxic therapy, with hyperuricemia, hyperkalemia,... (Review)
Review
BACKGROUND
Tumor lysis syndrome (TLS) is an oncologic emergency due to a rapid break down of malignant cells usually induced by cytotoxic therapy, with hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and serious clinical consequences such as acute renal injury, cardiac arrhythmia, hypotension, and death. Rapidly expanding knowledge of cancer immune evasion mechanisms and host-tumor interactions has significantly changed our therapeutic strategies in hemato-oncology what resulted in the expanding spectrum of neoplasms with a risk of TLS.
SUMMARY
Since clinical TLS is a life-threatening condition, identifying patients with risk factors for TLS development and implementation of adequate preventive measures remains the most critical component of its medical management. In general, these consist of vigilant laboratory and clinical monitoring, vigorous IV hydration, urate-lowering therapy, avoidance of exogenous potassium, use of phosphate binders, and - in high-risk cases - considering cytoreduction before the start of the aggressive agent or a gradual escalation of its dose. Key Messages: In patients with a high risk of TLS, cytotoxic chemotherapy should be given in the facility with ready access to dialysis and a treatment plan discussed with the nephrology team. In the case of hyperkalemia, severe hyperphosphatemia or acidosis, and fluid overload unresponsive to diuretic therapy, the early renal replacement therapy (RRT) should be considered. One must remember that in TLS, the threshold for RRT initiation may be lower than in other clinical situations since the process of cell breakdown is ongoing, and rapid increases in serum electrolytes cannot be predicted.
Topics: Acute Kidney Injury; Animals; Disease Management; Humans; Hyperkalemia; Hyperphosphatemia; Hyperuricemia; Incidence; Risk Factors; Tumor Lysis Syndrome
PubMed: 32998135
DOI: 10.1159/000509934 -
British Journal of Haematology Feb 2020Tumour lysis syndrome (TLS) is a significant complication of haematologic malignancies and their management. The syndrome consists of laboratory abnormalities either... (Review)
Review
Tumour lysis syndrome (TLS) is a significant complication of haematologic malignancies and their management. The syndrome consists of laboratory abnormalities either alone (laboratory TLS) or with clinical sequelae including renal failure, seizures, and arrhythmias (clinical TLS). Clinical TLS is a predictor for worse overall morbidity and mortality in cancer patients, but can be prevented. Thus, accurate prognostication is critical to appropriate management of patients at risk for TLS, and incorporates both disease factors (tumour type and burden) and patient factors (baseline renal insufficiency or hyperuricaemia). Strategies to prevent TLS include hydration and allopurinol in low- and intermediate-risk patients and rasburicase in high-risk patients.
Topics: Allopurinol; Fluid Therapy; Hematologic Neoplasms; Humans; Risk Factors; Tumor Lysis Syndrome
PubMed: 31774551
DOI: 10.1111/bjh.16278 -
British Journal of Haematology Oct 2004Tumour lysis syndrome (TLS) describes the metabolic derangements that occur with tumour breakdown following the initiation of cytotoxic therapy. TLS results from the... (Review)
Review
Tumour lysis syndrome (TLS) describes the metabolic derangements that occur with tumour breakdown following the initiation of cytotoxic therapy. TLS results from the rapid destruction of malignant cells and the abrupt release of intracellular ions, nucleic acids, proteins and their metabolites into the extracellular space. These metabolites can overwhelm the body's normal homeostatic mechanisms and cause hyperuricaemia, hyperkalaemia, hyperphosphaetemia, hypocalcaemia and uraemia. TLS can lead to acute renal failure and can be life-threatening. Early recognition of patients at risk and initiation of therapy for TLS is essential. There is a high incidence of TLS in tumours with high proliferative rates and tumour burden such as acute lymphoblastic leukaemia and Burkitt's lymphoma. The mainstays of TLS prophylaxis and treatment include aggressive hydration and diuresis, control of hyperuricaemia with allopurinol prophylaxis and rasburicase treatment, and vigilant monitoring of electrolyte abnormalities. Urine alkalinization remains controversial. Unfortunately, there have been few comprehensive reviews on this important subject. In this review, we describe the incidence, pathophysiological mechanisms of TLS and risk factors for its development. We summarise recent advances in the management of TLS and provide a new classification system and recommendations for prophylaxis and/or treatment based on this classification scheme.
Topics: Allopurinol; Humans; Tumor Lysis Syndrome; Water-Electrolyte Imbalance
PubMed: 15384972
DOI: 10.1111/j.1365-2141.2004.05094.x -
The Western Journal of Emergency... Mar 2019Oncologic emergencies may be seen in any emergency department and will become more frequent as our population ages and more patients receive chemotherapy. Life-saving... (Review)
Review
Oncologic emergencies may be seen in any emergency department and will become more frequent as our population ages and more patients receive chemotherapy. Life-saving interventions are available for certain oncologic emergencies if the diagnosis is made in a timely fashion. In this article we will cover neutropenic fever, tumor lysis syndrome, hypercalcemia of malignancy, and hyperviscosity syndrome. After reading this article the reader should be much more confident in the diagnosis, evaluation, and management of these oncologic emergencies.
Topics: Blood Viscosity; Emergencies; Emergency Treatment; Hematologic Diseases; Humans; Hypercalcemia; Neoplasms; Neutropenia; Tumor Lysis Syndrome
PubMed: 30881552
DOI: 10.5811/westjem.2018.12.37335 -
Blood Feb 2021Burkitt lymphoma (BL) is a highly aggressive, B-cell, non-Hodgkin lymphoma categorized into endemic, sporadic, and immunodeficiency-associated subtypes. BL has distinct... (Review)
Review
Burkitt lymphoma (BL) is a highly aggressive, B-cell, non-Hodgkin lymphoma categorized into endemic, sporadic, and immunodeficiency-associated subtypes. BL has distinct pathologic and clinical features, characterized by rapidly progressive tumors with high rates of extranodal involvement. Next-generation-sequencing analyses have further characterized the genomic landscape of BL and our understanding of disease pathogenesis, although these findings have yet to influence treatment. Although most patients are cured with intensive combination chemotherapy, given the paucity of randomized trials, optimal therapy has not been defined. Furthermore, treatment of elderly patients, patients with central nervous system involvement, or those with relapsed disease remains an unmet need. In this review, we highlight the clinical, pathologic, and genomic features, as well as standard and emerging treatment options for adult patients with BL.
Topics: Adult; Africa South of the Sahara; Allografts; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Biomarkers, Tumor; Burkitt Lymphoma; Central Nervous System; Disease Management; Endemic Diseases; Epstein-Barr Virus Infections; Europe; Gene Expression Profiling; Genes, myc; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Humans; Mutation; Neoplasm Proteins; Prognosis; Rituximab; Therapies, Investigational; Tumor Lysis Syndrome; United States
PubMed: 33171490
DOI: 10.1182/blood.2019004099 -
The New England Journal of Medicine Mar 2018Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia.
METHODS
In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group). The trial design did not include crossover to venetoclax plus rituximab for patients in the bendamustine-rituximab group in whom progression occurred. The primary end point was investigator-assessed progression-free survival.
RESULTS
After a median follow-up period of 23.8 months, the rate of investigator-assessed progression-free survival was significantly higher in the venetoclax-rituximab group (32 events of progression or death in 194 patients) than in the bendamustine-rituximab group (114 events in 195 patients); the 2-year rates of progression-free survival were 84.9% and 36.3%, respectively (hazard ratio for progression or death, 0.17; 95% confidence interval [CI], 0.11 to 0.25; P<0.001 by the stratified log-rank test). The benefit was maintained across all clinical and biologic subgroups, including the subgroup of patients with chromosome 17p deletion; the 2-year rate of progression-free survival among patients with chromosome 17p deletion was 81.5% in the venetoclax-rituximab group versus 27.8% in the bendamustine-rituximab group (hazard ratio, 0.13; 95% CI, 0.05 to 0.29), and the 2-year rate among those without chromosome 17p deletion was 85.9% versus 41.0% (hazard ratio, 0.19; 95% CI, 0.12 to 0.32). The benefit of venetoclax plus rituximab over bendamustine plus rituximab was confirmed by an independent review committee assessment of progression-free survival and other secondary efficacy end points. The rate of grade 3 or 4 neutropenia was higher in the venetoclax-rituximab group than in the bendamustine-rituximab group, but the rates of grade 3 or 4 febrile neutropenia and infections or infestations were lower with venetoclax than with bendamustine. The rate of grade 3 or 4 tumor lysis syndrome in the venetoclax-rituximab group was 3.1% (6 of 194 patients).
CONCLUSIONS
Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progression-free survival than bendamustine plus rituximab. (Funded by Genentech and AbbVie; ClinicalTrials.gov number, NCT02005471 .).
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Bridged Bicyclo Compounds, Heterocyclic; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Kaplan-Meier Estimate; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Neoplasm, Residual; Neutropenia; Recurrence; Rituximab; Sulfonamides; Tumor Lysis Syndrome; Young Adult
PubMed: 29562156
DOI: 10.1056/NEJMoa1713976 -
British Journal of Haematology May 2010Tumour lysis syndrome (TLS) is a life-threatening oncological emergency characterized by metabolic abnormalities including hyperuricaemia, hyperphosphataemia,... (Review)
Review
Tumour lysis syndrome (TLS) is a life-threatening oncological emergency characterized by metabolic abnormalities including hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. These metabolic complications predispose the cancer patient to clinical toxicities including renal insufficiency, cardiac arrhythmias, seizures, neurological complications and potentially sudden death. With the increased availability of newer therapeutic targeted agents, such as rasburicase (recombinant urate oxidase), there are no published guidelines on the risk classification of TLS for individual patients at risk of developing this syndrome. We convened an international TLS expert consensus panel to develop guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. Risk factors included biological evidence of laboratory TLS (LTLS), proliferation, bulk and stage of malignant tumour and renal impairment and/or involvement at the time of TLS diagnosis. An international TLS consensus expert panel of paediatric and adult oncologists, experts in TLS pathophysiology and experts in TLS prophylaxis and management, developed a final model of low, intermediate and high risk TLS classification and associated TLS prophylaxis recommendations.
Topics: Adult; Child; Decision Trees; Evidence-Based Medicine; Humans; Kidney; Leukemia; Lymphoma; Multiple Myeloma; Neoplasms; Risk Assessment; Tumor Lysis Syndrome
PubMed: 20331465
DOI: 10.1111/j.1365-2141.2010.08143.x