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Introduction: Tumor lysis syndrome (TLS) occurs frequently during induction therapy for acute lymphoblastic leukemia (ALL). Patients are categorized into intermediate- or high-risk based on the lactate dehydrogenase (LDH) value and white blood cell (WBC) count, according to an expert panel, although no effort has been made to analyze TLS in ALL and its potential consequences., Methods: We retrospectively analyzed TLS, variables associated with its occurrence, and its impact on overall survival (OS) and mortality during induction in a cohort of ALL patients in their first induction regimen., Results: A total of 138 patients were included, 52.9% were male and the median age at diagnosis was 34 years. Most of them were treated with hyper-CVAD (39.1%) or a modified CALGB 10403 regimen (37.7%). TLS was identified in 42 patients (30.4%), and half of them fulfilled criteria for clinical TLS (C-TLS). Median OS was the lowest in C-TLS patients. An LDH 3 times greater than its upper laboratory normal (ULN) value and a WBC count equal to or greater than 50×109/L were associated with TLS development, and being male, hyperuricemia and an LDH 3 times greater than its ULN value were associated with C-TLS development. C-TLS and acute kidney injury were associated with excess mortality during induction., Conclusion: TLS was identified in almost one-third of ALL patients during induction therapy. Different thresholds for LDH value and WBC count as well as other variables could identify patients at risk of developing this complication, which is associated with shorter OS. C-TLS confers a higher risk for mortality during induction., (© 2023 S. Karger AG, Basel.)

Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children's Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 10 9 /L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6-4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6-8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0-6.9 and OR = 5.4, 95% CI = 2.0-14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.

Background The recommended dose of rasburicase is quite expensive, thus limiting its use. Whether a lower dose of rasburicase would be equally effective for critically ill children, who often have more complicated situations and a higher risk of hospital death, is still unknown. Objective To explore the safety and efficacy of low-dose rasburicase in critically ill children with haematological malignancies who are at high risk of tumour lysis syndrome. Setting A single-centre retrospective cohort study. Method Children with haematological malignancies who had a history of rasburicase exposure during an intensive care unit stay were enrolled. Patients were divided into two groups according to the initial dosage of rasburicase: the standard-dose group (> 0.1 mg/kg/day) and the low-dose group (≤ 0.1 mg/kg/day). The adverse events and short-term prognosis of the two groups were compared. Results Thirty-seven children were selected, 22 in the standard-dose group and 15 in the low-dose group. The most common tumour type was Burkitt's lymphoma (81%), followed by acute lymphoblastic leukaemia (11%). All patients were at high risk of tumour lysis syndrome, and 73% of them had 3 or more tumour lysis syndrome risk factors. The uric acid levels of 90% of patients with hyperuricaemia returned to the normal range within 12 h (100% in the standard-dose group and 75% in the low-dose group, P = 0.083). Eighty-four percent of patients presented serious complications, including tumour lysis syndrome (73%), acute kidney injury (59%), renal replacement treatment (24%), respiratory failure (24%), disseminated intravascular coagulation (16%) and heart failure (11%). There was no significant difference in the incidence of serious complications between the two groups. The overall 7-day and 28-day survival rates after intensive care unit admission were 86% and 84%, respectively. The average length of stay in the intensive care unit was 9.92 ± 5.13 days. Neither the short-term mortality nor the length of stay in the intensive care unit were significantly different between the two groups. Conclusion Low-dose rasburicase is effective and may be an acceptable choice for critically ill children with haematological malignancies.

Background: Despite the effectiveness of combination antiretroviral therapy, persons living with human immunodeficiency virus (PLWHIV) remain at a high risk of developing non-Hodgkin lymphoma (NHL). We aimed to analyze the demographics and outcomes of the HIV-associated NHLs., Methods: Between 2005 and 2014, PLWHIV with NHLs were retrospectively enrolled at a tertiary referral center. Characteristics and survival were reviewed and analyzed., Results: Twenty-two HIV-associated NHLs were identified, with a median follow-up of 14 months (range, 0.1-139.7), including eight diffuse large B-cell lymphomas (DLBCLs), eight primary central nervous system lymphomas (PCNSLs), and six Burkitt's lymphomas (BLs). Nine patients (40.9%) were diagnosed with NHLs and HIV infection concurrently. The prognosis of DLBCL patients tended to be better prognosis than that of BL and PCNSL patients (median overall survival: not reached vs. 3.5 months, p = 0.056). Very early mortality (death within 14 days after NHL diagnosis) was noted in five patients (22.7%), and tumor lysis syndrome (TLS) is a predictive factor for very early mortality among PLWHIV (hazard ratio:11.3, 95% confidence interval: 1.1-114.4, p = 0.04)., Conclusion: Management of the early treatment phase of HIV-associated NHLs remains a major challenge. Careful intervention to patients with TLS might be the key to improve treatment outcomes.

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., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: To evaluate the results of an intensive polychemotherapy regimen for Burkitt lymphoma (BL) in sub-Saharan African pediatric centers., Patients and Methods: Children with advanced-stage BL (stages II bulky, III, and IV) treated with the GFAOP-Lymphomes Malins B (GFALMB) 2009 protocol in 7 centers between April 2009 and September 2015 were prospectively registered. Treatment regimen contained a prephase with cyclophosphamide followed by 2 induction courses (cyclophosphamide, vincristine, prednisone, high-dose methotrexate [HDMTX]), 2 consolidation courses (cytarabine, HDMTX), and a maintenance phase only for stage IV. HDMTX was given at the dose of 3 g/m 2 ., Results: Four hundred patients were analyzed: 7% had stage II bulky, 76% stage III, and 17% stage IV disease. Median age was 7.3 years, and sex ratio was 1.9:1 (male:female). A total of 221 patients received the whole protocol treatment and 195 achieved complete remission (CR), 11 of them after a second-line treatment. Treatment abandonment rate was 22%. One hundred twenty-five patients died, of whom 49 deaths were related to treatment toxicity. A total of 275 patients are alive, including 25 despite treatment abandonment, but only 110 are known to be in CR with a follow-up > 1 year, indicating a high rate of loss to follow-up. Twelve-month overall survival (OS) was 60% (95% CI, 54% to 66%) and 63%, 60%, and 31%, respectively, for stage II bulky, III, and IV. Patients with stage III disease who started second induction course within 34 days had OS of 76%, versus 57% ( P = .0062) beyond 34 days., Conclusion: The GFA-LMB2009 protocol improved patients' survival. Early dose intensity of treatment is a strong prognostic factor. Improving supportive care and decreasing loss to follow-up are crucial.

T cell non-Hodgkin lymphomas (T-NHLs) are aggressive malignancies which have a high risk of life-threatening complications. However, their prognosis in the intensive care unit (ICU) setting has not yet been assessed. We conducted a study including 87 ICU patients either with newly diagnosed T-NHLs or those undergoing first-line therapy admitted between January 1, 2000, and December 31, 2014. The primary subtypes were peripheral T cell lymphoma (PTCL) (n = 41, 47%), anaplastic large-cell lymphoma (ALCL) (n = 13, 15%), and adult T-leukaemia/lymphoma (ATLL) (n = 11, 13%). Six in every ten patients had malignancy-related complications (haemophagocytic syndrome 37%, tumour lysis syndrome 18% and hypercalcaemia 9%), while infections accounted for one quarter of ICU admissions. Nine fungal infections were documented, including six invasive aspergillosis. Urgent chemotherapy was started in the ICU in 59% of the patients, and urgent surgery was required in 13%. ICU and day-90 mortality were 22% and 41%, respectively. Multivariate analysis showed that SOFA score at day 1, age, sepsis and haemophagocytic syndrome were independent predictors of day-90 mortality. Compared to 66 ICU-matched controls with non-Hodgkin B cell lymphomas, patients with T-NHLs had a similar ICU survival. Overall survival rates of patients with T cell NHLs and B cell NHLs were 20% and 46%, respectively (hazard ratio for death associated with T cell NHLs 2.00 [1.12-3.58]). Patients with T cell NHLs had a very poor long-term outcome. Although the high rate of short-term survival suggests that an ICU trial is a reasonable option for patients newly diagnosed for the malignancy, extended stay in the ICU or further readmission should be considered only for highly selected patients who respond to the haematological treatment.

This study aimed to investigate the treatment strategy, prognostic factors, and risk factors of early death in elderly patients (age ≥ 65 years) with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Data from elderly patients diagnosed with DLBCL between 2008 and 2014 were collected for analysis. Patients who were younger and had a better performance status were more likely to receive intensive frontline treatment. The median progression-free survival (PFS) and overall survival were 15 and 21 months, respectively. Anthracycline-containing chemotherapy achieved a higher remission rate and showed a trend towards better overall survival but a higher risk of severe neutropenia. Multivariate analysis revealed that very old age (≥81 years), a high-risk age-adjusted international prognostic index (aaIPI) score, and bone marrow involvement were associated with poorer PFS and overall survival. Progression of lymphoma was the major cause of death in the study population. In addition, approximately 25% of patients died within 120 days of being diagnosed. The risk factors for early mortality included very old age, a high-risk aaIPI score, and bone marrow involvement. The appearance of symptoms or signs of tumour lysis syndrome at diagnosis was associated with a trend towards early death.

Background: Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Previous reviews did not find clear evidence of benefit of urate oxidase in children with cancer. This review is the second update of a previously published Cochrane review., Objectives: To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies., Search Methods: In March 2016 we searched CENTRAL, MEDLINE, Embase, and CINAHL. In addition, we searched the reference lists of all identified relevant papers, trials registers and other databases. We also screened conference proceedings and we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis., Selection Criteria: Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy., Data Collection and Analysis: Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data., Main Results: We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. No new studies were identified in the update. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT did not evaluate the primary outcome (incidence of clinical TLS). It showed no clear evidence of a difference in mortality (both all-cause mortality (Fisher's exact test P = 0.23) and mortality due to TLS (no deaths in either group)), renal failure (Fisher's exact test P = 0.46), and adverse effects between the treatment and the control groups (Fisher's exact test P = 1.0). The frequency of normalisation of uric acid at four hours (10 out of 10 participants in the treatment group versus zero out of nine participants in the control group, Fisher's exact test P < 0.001) and area under the curve of uric acid at four days (MD -201.00 mg/dLhr, 95% CI -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group.One CCT evaluated the primary outcome; no clear evidence of a difference was identified between the treatment and the control groups (RR 0.77, 95% CI 0.44 to 1.33; P = 0.34). Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); no clear evidence of a difference in all-cause mortality was identified between the groups (RR 0.19, 95% CI 0.01 to 3.42; P = 0.26). Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs: MD -3.80 mg/dL, 95% CI -7.37 mg/dL to -0.24 mg/dL; P = 0.04), three days (two CCTs: MD -3.13 mg/dL, 95% CI -6.12 mg/dL to -0.14 mg/dL; P = 0.04), four days (two CCTs: MD -4.60 mg/dL, 95% CI -6.39 mg/dL to -2.81 mg/dL; P < 0.00001), and seven days (one CCT: MD -1.74 mg/dL, 95% CI -3.01 mg/dL to -0.47 mg/dL; P = 0.007) after therapy, but not one day (three CCTs: MD -3.00 mg/dL, 95% CI -7.61 mg/dL to 1.60 mg/dL; P = 0.2), five days (one CCT: MD -1.02 mg/dL, 95% CI -2.24 mg/dL to 0.20 mg/dL; P = 0.1), and 12 days (one CCT: MD -0.80 mg/dL, 95% CI -2.51 mg/dL to 0.91 mg/dL; P = 0.36) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03).Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg). The primary outcome was not evaluated. No clear evidence of a difference in mortality (all-cause mortality (Fisher's exact test P = 1.0) and mortality due to TLS (no deaths in both groups)) and renal failure (no renal failure in both groups) was identified. It demonstrated no clear evidence of a difference in uric acid normalisation (RR 1.07, 95% CI 0.89 to 1.28; P = 0.49) and uric acid level at four hours (MD 8.10%, 95% CI -0.99% to 17.19%; P = 0.08). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no clear evidence of a difference between treatment groups was identified (RR 0.54, 95% CI 0.12 to 2.48; P = 0.42).The quality of evidence ranks from very low to low because of imprecise results, and all included trials were highly susceptible to biases., Authors' Conclusions: Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical TLS, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

Introduction and Objective: Tumour lysis syndrome (TLS) is an uncommon complication in solid tumors following treatment initiation, and its spontaneous development (STLS) is exceptional. In this study, we analyse the main clinical and prognostic features of a case series with TLS and STLS., Material and Methods: Observational retrospective study in which we included all patients with solid tumours diagnosed with TLS and STLS over a period of 16 years, according to Cairo-Bishop criteria., Results: Nineteen patients were included in the study (mean age 63±16 years): 10 patients (53%) with TLS, and 9 (47%) STLS. The primary tumour in 8 cases (42%) was lung cancer. All patients had severe renal impairment at the time of diagnosis along with hyperuricemia (16±6mg/dl) and hyperkalemia (6±0.9mmol/l). Despite treatment with intravenous fluids, urinary alkalinisation and rasburicase, 3 patients (16%) required dialysis, and 12 (63%) died during the follow-up period., Conclusions: The development of TLS in solid tumors is associated with increased mortality and therefore, a high index of suspicion is essential for early diagnosis and treatment initiation., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Tumor lysis syndrome (TLS) is a life threatening emergency due to destruction and massive release of intracellular metabolites from cancer cells often resulting in acute kidney injury (AKI), sometimes severe enough to require dialysis (AKI-D). The impact of dialysis requirement in AKI has not been explored. We utilized data from the Nationwide Inpatient Sample and using International Classification of Diseases, 9th Revision, diagnoses codes for TLS, AKI and dialysis, evaluated the incidence, risk factors and impact of AKI-D on mortality, adverse discharge and length of stay (LOS). Survey multivariable logistic regression was used to compute adjusted Odds Ratios (aOR and 95% confidence intervals (CI). An estimated 12% (2,919) of all TLS hospitalizations (n = 22 875) develop AK-D. After adjustment for confounders, AKI-D was associated with greater odds of mortality (aOR 1.98; (95% CI 1.60-2.45)), adverse discharge (aOR 1.63 (95% CI 1.19-2.24)) and longer LOS (19 vs 14.6 days; P < 0.01) compared with those without AKI-D. Further studies to evaluate the association of AKI-D on long-term outcomes in patients with TLS are needed., (© 2016 Asian Pacific Society of Nephrology.)

Background: Hyperleucocytosis is associated with higher morbidity and mortality related to possible development of leucostasis, tumour lysis syndrome and/or disseminated intravascular coagulation. There is insufficient evidence of the need for leukocytapheresis during early treatment of hyperleucocytosis, and its efficiency remains controversial, although leucoreduction is a measure that can prevent adverse events and death. The aim of this study was to analyse the safety and effectiveness of therapeutic leukocytapheresis and its influence on early mortality in our case series, adjusted to independent mortality risk factors described in the literature., Materials and Methods: This was a retrospective review (June 2003-June 2012) of procedures carried out for the treatment of hyperleucocytosis at the Haematology and Haemotherapy Service of Miguel Servet University Hospital. The patients' data and technical information were prospectively registered for each leukocytapheresis session., Results: Thirteen patients underwent a total of 27 leukocytapheresis procedures. After an average of two sessions, a statistically significant drop in the initial leucocyte counts was observed (p<0.01), as well as a relevant drop in lactate dehydrogenase levels. The only analytical value statistically related to early mortality in univariate analysis was initial creatinine level greater than 1.2 mg/dL (p=0.012, OR=2.5)., Discussion: Despite the small size and limited homogeneity of our case series, we can conclude that leukocytapheresis is a safe and effective therapeutic measure for leucoreduction in haematological pathologies of any lineage, particularly in patients without acute myeloid leukaemia. Patients with acute myeloid leukaemia had worse outcomes within 6 months of having finished leukocytapheresis sessions, as well as in terms of mean global survival and mean time of mortality. However, global mortality rates were similar in patients with or without acute myeloid leukaemia.

Background: Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is effective in reducing serum uric acid, the build-up of which causes TLS. It is uncertain whether high-quality evidence exists to support its routine use in children with malignancies., Objectives: To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies., Search Methods: This is an update of the original review. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library issue 1, 2013), MEDLINE (1966 to February 2013), Embase (1980 to February 2013), and CINAHL (1982 to February 2013). In addition, we searched the reference lists of all identified relevant papers. We also explored other internet sources (updated search on 26 February 2013): the NHS' National Research Register, the US National Institutes of Health Ongoing Trials Register, the metaRegister of Controlled Trials, and ProQuest Dissertations & Theses Database. We also screened conference proceedings of the American Society of Clinical Oncology, the European Society for Medical Oncology, and the International Society of Paediatric Oncology meetings from 1993 to 2012. Finally, we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis., Selection Criteria: Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy., Data Collection and Analysis: Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data., Main Results: We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT showed no significant difference in mortality (both all-cause mortality and mortality due to TLS), renal failure, and adverse effects between the treatment and the control groups. The frequency of normalisation of uric acid at four hours (Fisher's exact test P < 0.001) and area under curve of uric acid at four days (MD -201.00 mg/dLhr, 95% confidence interval (CI) -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group. The trial did not evaluate the primary outcome (incidence of clinical TLS).Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); all-cause mortality was not significantly different between the groups. Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs), three days (two CCTs), four days (two CCTs), and seven days (one CCT) after therapy, but not one day (three CCTs), five days (one CCT), and 12 days (one CCT) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03). One CCT evaluated the primary outcome; no significant difference was identified.Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated no significant difference in uric acid normalisation and uric acid level at four hours). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no significant difference between treatment groups was identified. No significant difference in mortality (all-cause mortality and mortality due to TLS) and renal failure was identified. The primary outcome was not evaluated.All included trials were highly susceptible to biases., Authors' Conclusions: Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical tumour lysis syndrome, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

Tumor lysis syndrome (TLS) describes the clinical and laboratory sequelae that result from the rapid release of intracellular contents of dying cancer cells. It is characterized by the release of potassium, phosphorous, and nucleic acids from cancer cells into the blood stream, with the potential to cause hyperkalemia; hyperphosphatemia and secondary hypocalcemia; hyperuricemia; AKI; and, should usual homeostatic mechanisms fail, death. TLS most commonly follows treatment of hematologic malignancies, such as acute lymphocytic or lymphoblastic leukemia, acute myeloid leukemia, and Burkitt lymphoma, but also occurs after treatment of other bulky or rapidly growing tumors, particularly if the patient is highly sensitive to the effects of cytotoxic chemotherapy. Prevention and treatment depend on prompt recognition of patients at risk, volume repletion, allopurinol, rasburicase (a novel recombinant urate oxidase), and, when indicated, dialysis.

Background: Tumor lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is highly effective in reducing serum uric acid. It is uncertain whether high quality evidence exists to support its routine use in children with malignancies., Objectives: We aimed to determine the effectiveness and safety of urate oxidase in the prevention and treatment of TLS in children with malignancies., Search Strategy: We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009) and CINAHL (1982 to 2009)., Selection Criteria: Randomized controlled trials (RCT) and controlled clinical trials (CCT) evaluating urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy., Data Collection and Analysis: Two review authors independently extracted trial data and assessed individual trial quality. We used relative risk (RR) for binary data and mean difference (MD) for continuous data., Main Results: We included five trials, involved 336 patients in the treatment groups and 458 patients in the control groups. One RCT and three CCTs compared urate oxidase and allopurinol. Two trials tested Uricozyme and two tested rasburicase for the prevention of TLS. The RCT showed no significant difference in mortality or renal failure between the treatment and the control groups. The frequency of normalization of uric acid (RR 19.09, 95% CI 1.28 to 285.41) and area under curve of uric acid (MD -201, 95% CI to -258.05 to -143.95) were significantly better in the treatment group. One patient developed hemolysis. One CCT reported significantly lower mortality due to TLS (RR 0.05, 95% CI 0.00 to 0.89) and lower incidence of renal failure (RR 0.13, 95% CI 0.05 to 0.35) in the treatment group. Another CCT found significantly lower uric acid in the treatment group at 72 hours (MD -98.33, 95% CI -170.66 to -26) and 168 hours (MD -103.67, 95% CI -179.00 to -28.34). All included trials are highly susceptible to biases.Another included RCT with 30 patients compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated similar efficacy in the reduction of uric acid. Adverse events occurred in 20% of patients, including hemolysis, hypersensitivity and anemia., Authors' Conclusions: Although urate oxidase might be effective in reducing serum uric acid, it is still unclear whether this translates into a reduction in mortality or renal failure. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing renal failure or mortality from TLS against the potential risk of adverse effects.

Acute tumor lysis syndrome (ATLS) caused by the destruction of malignant cells leads to metabolic abnormalities, which may either remain isolated (biological ATLS) or subsequently lead to renal dysfunction (clinical ATLS). We compared hospital and 6-month survival in patients with ATLS with hematological malignancies with or without acute renal injury. Sixty-three patients (median age, 50 years; range, 32-64) were included with ATLS. Twenty-eight had no ARI (including 17 (61%) who subsequently required dialysis) whereas 35 had an ATLS-related ARI (including 31 (89%) who required dialysis). Acute leukemia (n = 28) and lymphoma (n = 30) were the main malignancies. All patients had high tumor burdens. Hospital and 6-month mortality rates were significantly lower in patients without ARI (7% and 21%, respectively) than in the ATLS-related renal injury group (51% and 66%). After adjustment for acute disease severity, presence of ARI at ICU admission was associated with higher hospital mortality (odds ratio, 10.41; 95% confidence interval, 2.01-19.170; p = 0.005) and 6-month mortality (odds ratio, 5.61; 95% confidence interval, 1.64-54.66; p = 0.006), compared to patients without renal injury. Our study suggests that in patients with ATLS, ICU management when acute renal injury is present is associated with higher short- and long-term mortality.

Spontaneous tumour lysis syndrome (STLS) inducing acute uric acid nephropathy, a rare and neglected disease, presents more insidiously than conventional post-treatment tumour lysis syndrome. Although STLS is a serious and potentially fatal complication in patients with neoplastic disorders, few investigations have addressed the relevance of clinical and laboratory features in assessing prognosis. A retrospective study was conducted, reviewing the records of all patients who developed acute renal failure (ARF) at Chang Gung memorial hospital between 1 July 1999 and 30 June 2003. STLS-induced acute uric acid nephropathy was identified in 12 of 1072 ARF patients (1.1%) during the study period. All patients had advanced stage tumours with large tumour burden, and 66.7% of cases had abdominal organ involvement. All 12 hyperuricemic patients became oliguric despite conservative therapy, and remained hyperuricemic (21.6 +/- 5.2 mg/dl) before dialysis therapy. Diuresis developed in eight patients (66.7%), with associated resolution of hyperuricemia, azotemia and metabolic derangements following dialysis initiation. Overall hospital mortality was 58.3%. Death in most patients was related to hyponatremia and hypoalbuminemia on admission. The serum sodium was found to have the best Youden index (0.86) and highest overall prediction accuracy (93%). Moreover, serum sodium and serum albumin for individual patients were significantly and positively correlated (r = 0.617, p = 0.032). This investigation confirms a grave prognosis for cancer patients with STLS inducing acute uric acid nephropathy. Hyponatremia and hypoalbuminemia on the first day of admission indicate poor prognosis in such patients.

Background: Despite the prophylactic use of allopurinol, tumor lysis syndrome (TLS)-related morbidity and mortality still occur in a number of patients with acute myeloid leukemia (AML). The aim of this study was: (i) to analyze the incidence and outcome of TLS in a large series of patients with AML receiving hyperhydration and allopurinol, (ii) to identify risk factors for TLS, and (iii) to develop a prognostic scoring system for estimating individual risk of TLS., Design and Methods: The study included 772 adult patients with AML receiving induction chemotherapy between 1980 and 2002. TLS was divided into laboratory TLS (LTLS) or clinical TLS (CTLS). The population study was randomly divided into training and test subsets, so that a prognostic model for CTLS was developed in one set and validated in the other., Results: Overall, 130 patients (17%) developed TLS (5% CTLS and 12% LTLS). Unlike LTLS, CTLS was associated with a higher rate of death from induction therapy. Multivariate analysis showed that pretreatment serum lactate dehydrogenase (LDH) levels above laboratory normal values, creatinine >1.4 mg/dL, uric acid >7.5 mg/dL and white blood cell (WBC) counts >25 x 10(9)/L were independent risk factors for CTLS and LTLS. The scoring system, based on pretreatment WBC counts, and uric acid and LDH serum levels, had excellent discrimination and was accurate for predicting CTLS and LTLS., Conclusions: TLS is frequently observed in AML patients during induction therapy. Only the development of CTLS had an impact on higher mortality rate from induction therapy. The scoring system derived from this study can be used to obtain an accurate estimate of the individual risk of TLS, allowing for risk-adapted prophylaxis against this complication.

We report a case and autopsy findings of posterior leukoencephalopathy (PL) developing during induction chemotherapy for B-cell acute lymphoblastic leukaemia (B-ALL) complicated by tumour lysis syndrome. PL may present with seizures, headache, altered mental status and occipital blindness, associated with transient parieto-occipital abnormalities on neuro-imaging studies. Precipitants include immunosuppressive agents, renal insufficiency, hypertension and fluid retention. It has also been reported in association with pre-eclamptic and eclamptic states, nephrotic syndrome and following liver and bone marrow transplantation. Only rare cases of PL developing during treatment for haematological malignancy have been reported and to our knowledge it has not been previously reported in association with tumour lysis syndrome. Since the condition is generally regarded as being fully reversible few autopsy findings have been reported.

Tumour lysis syndrome (TLS) is caused by rapid breakdown of malignant cells resulting in electrolyte disturbances and acute renal failure. TLS has rarely been described in patients with acute myelogenous leukaemia (AML). Between November 1997 and July 2001, 114 consecutive adult AML patients aged <60 yr received induction chemotherapy consisting of cytosine arabinoside 1.5 g m(-2) q 12 h x 12 doses and daunorubicin 45 mg m(-2) d(-1) x 3 doses. During induction chemotherapy (CT), seven patients (6.1%, 95% CI 2.5-12.2) developed fulminant TLS, resulting in acute renal failure; five of these seven patients had inversion of chromosome 16 [inv(16)(p13;q22)], and one patient had a biological equivalent [t(16,16)(p13;q22)]. Four of the TLS patients underwent leukapheresis for a presenting white blood cell (WBC) count > 100 x 10(9) L(-1) prior to commencing chemotherapy, and six patients subsequently required haemodialysis for a median of 2 (range 1-8) wk. One TLS patient died of intracerebral hemorrhage on day 10 and another patient of multiorgan failure on day 17. Of the other five patients, all entered a complete remission (CR) and recovered normal renal function. Four patients remain in continuous CR [median follow-up 20 (range 12-25) months]. One patient relapsed at 12 months and again developed TLS on re-induction. In univariate analysis, TLS patients were more likely to have an elevated presentation and pre-chemotherapy WBC counts, elevated serum creatinine, and uric acid levels at presentation, as well as an inv(16). In multivariate analysis, only serum creatinine and inv(16) remained statistically significant (P < 0.001 for each). Patients with an inv(16) are a unique AML subgroup at high risk for fulminant TLS.

Purpose: To evaluate the frequency of metabolic complications and dialysis due to tumor lysis syndrome in patients with B-cell advanced-stage non-Hodgkin's lymphoma (NHL) and L3 leukemia at initiation of chemotherapy including the use of urate-oxidase., Patients and Methods: Retrospective review of the clinical records of 410 patients with stage III and IV B-cell NHL and L3 leukemia treated in France and prospectively registered in the LMB89 protocol., Results: During the first week of chemotherapy, only 34 of 410 patients recorded metabolic problems that included hypocalcemia (< 70 mg/dl) in 24 patients, hyperphosphatemia (> 6.5 mg/dl) in 28 and elevation of creatinine > or = 2 SD in 16. Six patients underwent dialysis for life-threatening problems and a seventh as a preventive measure. In the other 27 cases, metabolic problems were successfully resolved using urate-oxidase in combination with alkaline hyperhydration. Among the 410 patients, one case of hemolysis was reported and there was no severe allergic reaction to urate-oxidase., Conclusions: Only 1.7% of patients in our study receiving urate-oxidase during their induction chemotherapy needed renal dialysis. Urate-oxidase was well tolerated, and used as prophylaxis and/or treatment of hyperuricemia and tumor lysis syndrome consistently gave a lower rate of renal and metabolic complications than in other series of similar patients.

Burkitt's acute lymphocytic leukemia is a rare type of adult ALL, probably difficult to distinguish from disseminated Burkitt's lymphoma involving the bone marrow. This tumor is highly proliferative and tends to involve the CNS at diagnosis or early during the disease course. It shows rapid chemosensitivity, initially leading to the risk of severe acute tumor lysis syndrome. Principles of its treatment, by comparison with the other types of ALL, include: 1. A low-dose chemotherapy prephase to prevent acute tumor lysis syndrome. 2. Multiagent chemotherapy using high-dose cyclophosphamide, an anthracycline, high-dose MTX, high-dose ara-C, and probably VP16. A short and intensive treatment (6 to 8 months) without maintenance is indicated. 3. Early intensive CNS treatment, with multiple triple intrathecal injections, high-dose MTX, and high-dose ara-C, and possibly cranial irradiation. Autologous or allogeneic stem cell transplantation do not seem to be useful in first CR. Using such approaches, recent results suggest that about two thirds of L3ALL in adults can be cured, more than in any other type of adult ALL.

Objective: Tumor lysis syndrome and renal failure remain important complications early in the course of therapy for pediatric Non-Hodgkin's lymphoma (NHL), frequently leading to therapeutic alterations. In the presented series, children with NHL and tumor lysis syndrome are retrospectively analysed regarding clinical features of acute renal failure and its implications on therapy., Patients and Methods: From 4/1990 to 10/1997, 1192 patients diagnosed of any form of NHL have been registered in the NHL-BFM trials. 63 of these patients were reported to have suffered from impaired renal function and/or tumor lysis syndrome before or during initial treatment. Clinical data of these patients were analysed regarding diagnosis, stage, tumor mass, therapy and complications., Results: 62 of 63 patients with impaired renal function and/or tumor lysis syndrome were diagnosed of Burkitt's lymphoma or B-ALL; 58 (92%) of these patients had advanced stages of disease and high LDH-levels (> 500 U/l). 43 of 63 patients had already signs of impaired renal function at admission. Hyperuricemia was the commonest cause of impaired renal function. Renal infiltration or enlargement was observed in 27 of 63 patients. 6 patients were diagnosed of urinary tract obstruction. 25 patients required hemodialysis. Despite improved renal function before administration of MTX, 21 of 63 patients suffered from protracted MTX-elimination during the first course of therapy. 7 of 63 patients (11%) with tumor lysis syndrome died of sepsis after the first course of therapy, another two patients died within 48 hours of therapy due to electrolyte imbalances., Conclusions: In pediatric NHL-patients, Burkitt's lymphoma and B-ALL appear to be the commonest cause of metabolic complications early in chemotherapy. Patients with advanced stages and large tumor mass are at high risk for renal failure. Impaired renal function predisposes patients to further complications and toxic death. Prophylactic use of urate-oxidase in all patients with advanced stage NHL might limit the incidence of tumor lysis syndrome. Prospective studies on renal function prior to and during therapy are required in order to develop a clinical profile reliably detecting patients at risk for developing renal failure and subsequent complications.