Acute kidney injury in children with lymphoma.

OBJECTIVE: To analyze the epidemiology of acute kidney injury (AKI) in children with lymphoma and to assess the incidence, risk profile of AKI, and effects on renal function in children with lymphoma during their first 30 days of hospitalization. MATERIALS AND METHODS: This was a retrospective screen of electronic hospital and laboratory databases to select hospitalized children who were first diagnosed and treated for lymphoma at Beijing Children's Hospital between 2020 and 2021. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. We analyzed the incidence and risk factors for AKI in children with lymphoma during their first 30 days of hospitalization. We also analyzed mortality rate and the incidence of kidney recovery over a 1-year follow-up period. RESULTS: Of the 295 children with lymphoma (which were all non-Hodgkin lymphoma), 42 (16.5%) experienced AKI events during the first their 30 days of hospitalization. The proportion of patients with lymphoma clinical stage 4 was higher in the AKI group than in the non-AKI group (66.7 vs. 43.7%, p < 0.05). Tumor lysis syndrome (TLS), lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma. Severe AKI was associated with TLS, sepsis, and a higher need for intensive care. Over 1-year of follow-up, none of the survivors developed impaired renal function or proteinuria. However, the mortality of children in the AKI group was significantly higher than that in the non-AKI group (p < 0.05). CONCLUSION: TLS, lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma during the first 30 days of hospitalization. Clinicians should increase their awareness of AKI in hospitalized patients with lymphoma.

Daily serum phosphate increase as early and reliable indicator of kidney injury in children with leukemia and lymphoma developing tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) and its most serious complication, acute kidney injury (AKI) are one of the emergency conditions in onco-hematology. It is difficult to predict the degree of kidney involvement. Therefore, we studied children with leukemia and lymphoma treated in four Hungarian tertiary centers (inpatient university clinics) retrospectively (2006-2016) from a nephrological aspect. METHOD: Data of 31 pediatric patients were obtained from electronic- and paper-based medical records. Physical status, laboratory test results, treatments, and outcomes were assessed. Patients were analyzed according to both "traditional" TLS groupings, as laboratory TLS or clinical TLS, and nephrological aspect based on pRIFLE classification, as mild or severe AKI. RESULTS: Significant differences were found between the changes in parameters of phosphate homeostasis and urea levels in both classifications. Compared to age-specific normal phosphate ranges, before the development of TLS, hypophosphatemia was common (19/31 cases), while in the post-TLS period, hyperphosphatemia was observed (26/31 cases) most frequently. The rate of daily change in serum phosphate level was significant in the nephrological subgroups, but peaks of serum phosphate level show only a moderate increase. The calculated cut-off value of daily serum phosphate level increased before AKI was 0.32 mmol/L per ROC analysis for severe TLS-AKI. The 24-h urinalysis data of eight patients revealed transiently increased phosphate excretion only in those patients with TLS in whom serum phosphate was elevated in parallel. CONCLUSION: Daily serum phosphate level increase can serve as a prognostic factor for the severity of pediatric TLS, as well as predict the severity of kidney involvement. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prevention and Treatment of Tumor Lysis Syndrome in the Era of Onco-Nephrology Progress.

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.

Fifteen-minute consultation: Initial management of suspected acute leukaemia by non-specialists.

Leukaemia is the most common cancer of childhood. Most children with a new diagnosis of leukaemia are clinically stable at initial presentation. However, there are a number of life-threatening complications that have to be considered and monitored for. These complications include sepsis, tumour lysis syndrome, mediastinal masses, bleeding and pain. The aim of this article is to equip the general paediatrician with a framework for managing children with suspected leukaemia, prior to transfer to the primary treatment centre. The presentation, diagnosis and definitive treatment of acute leukaemia is not in the remit of this article.

Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia with Novel Targeted Agents.

Tumor lysis syndrome (TLS) is an uncommon but potentially life-threatening complication associated with the treatment of some cancers. If left untreated, TLS may result in acute renal failure, cardiac dysrhythmia, neurologic complications, seizures, or death. Tumor lysis syndrome is most commonly observed in patients with hematologic malignancies with a high proliferation rate undergoing treatment with very effective therapies. In chronic lymphocytic leukemia (CLL), historically, TLS has been observed less often, owing to a low proliferation rate and slow response to chemotherapy. New targeted therapies have recently been approved in the treatment of CLL, including the oral kinase inhibitors, idelalisib and ibrutinib, and the B-cell lymphoma-2 protein inhibitor, venetoclax. Several others are also under development, and combination strategies of these agents are being explored. This review examines the diagnosis, prevention, and management of TLS and summarizes the TLS experience in CLL clinical trials with newer targeted agents. Overall, the risk of TLS is small, but the consequences may be fatal; therefore, patients should be monitored carefully. Therapies capable of eliciting rapid response and combination regimens are increasingly being evaluated for treatment of CLL, which may pose a higher risk of TLS. For optimal management, patients at risk for TLS require prophylaxis and close monitoring with appropriate tests and appropriate management to correct laboratory abnormalities, which allows for safe and effective disease control. IMPLICATIONS FOR PRACTICE: Tumor lysis syndrome (TLS) is a potentially fatal condition observed with hematologic malignancies, caused by release of cellular components in the bloodstream from rapidly dying tumor cells. The frequency and severity of TLS is partly dependent upon the biology of the disease and type of therapy administered. Novel targeted agents highly effective at inducing rapid cell death in chronic lymphocytic leukemia (CLL) may pose a risk for TLS in patients with tumors characterized by rapid growth, high tumor burden, and/or high sensitivity to treatment. In this review, prevention strategies and management of patients with CLL who develop TLS are described.

Single 4.5 mg fixed-dose of rasburicase for hyperuricemia associated with tumor lysis syndrome.

Rasburicase is a recombinant urate oxidase enzyme administered for treatment of hyperuricemia associated with tumor lysis syndrome. Studies demonstrate effectiveness of single fixed-dose rasburicase as compared to the FDA-approved dose of 0.2 mg/kg intravenously daily for up to five days. Doses in these studies range from 1.5 mg to 7.5 mg. Our study evaluated outcomes in patients who received single 4.5 mg fixed-dose rasburicase. This retrospective, IRB-approved chart review evaluated adult oncology subjects who received fixed-dose rasburicase between January 2007 and April 2014. The primary outcome was percentage of patients with normalization of uric acid (level <8 mg/dL within 24 h) after a single 4.5 mg fixed-dose of rasburicase. Secondary objectives were incidence of initial failure of fixed-dose rasburicase and normalization of uric acid in overweight (body mass index ≥25 kg/m2) versus non-overweight patients. Initial failure was defined as need for additional doses or progression to dialysis within one week of the initial fixed-dose. In the 128 patients included, the mean baseline uric acid level was 14.84 mg/dL. Of the 112 patients with a follow-up uric acid level, 68% achieved normalization within 24 h of rasburicase administration. Thirty-eight patients received additional treatment: 10 received additional dose(s) and 28 underwent dialysis. Normalization of uric acid in overweight versus non-overweight patients was 66% and 73%, respectively. Overall, a single 4.5 mg fixed-dose of rasburicase effectively normalized uric acid in 68% of patients within 24 h. Further studies are needed to determine the optimal single fixed-dose necessary for treatment response across all patients.

Spurious Thrombocytosis Caused by Tumor Cell Lysis in a Patient with Acute Monocytic Leukemia.

BACKGROUND: Tumor lysis syndrome can occur after treatment of fast-growing cancers. Early detection of tumor lysis is crucial to minimize the toxic effects on organs and potentially life-threatening complications. METHODS: A patient with acute monocytic leukemia presented with spurious thrombocytosis. A peripheral blood smear was stained with alpha-naphthyl butyrate esterase to discriminate tumor cell fragments from platelets. RESULTS: Peripheral blood smears showed widespread leukemic cell fragmentation. Tumor lysis syndrome (TLS) after treatment for acute monocytic leukemia was diagnosed. The patient underwent chemo- and radiotherapy followed by umbilical cord blood transplantation and remains symptom-free two years after transplantation. CONCLUSIONS: For patients with thrombocytosis accompanied by bizarre scatter-grams on automatic hematologic analyzers, further diagnostic procedures should be performed to determine the exact cause of thrombocytosis.

The efficacy of febuxostat 10 mg for the prevention of hyperuricemia associated with tumor lysis syndrome (TLS) in Japanese patients with non-Hodgkin's lymphoma
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Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. The control of serum uric acid level (UA) is important for prevention of TLS. Febuxostat has demonstrated its superiority over allopurinol in decreasing UA level. We retrospectively evaluated the efficacy of febuxostat 10 mg in prevention of hyperuricemia associated with TLS (HU-TLS) in 12 patients with non-Hodgkin's lymphoma (NHL). Mean UA levels were found to significantly decrease (p = 0.003). HU-TLS was prevented in all patients. Thus, febuxostat 10 mg is effective in prevention of HU-TLS. Future study is need to determine whether the incidence of HU-TLS change with dosage of febuxostat.
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[Tumor lysis syndrome in a pregnancy complicated with acute lymphoblastic leukemia]. / Síndrome de lisis tumoral en un embarazo complicado con leucemia linfoblástica aguda.

Acute leukemia is rare during pregnancy, affects about 1 in 75,000 pregnancies, of all leukemias diagnosed only 28% are acute lymphoblastic leukemia, this is a risk factor to develop spontaneous tumor lysis syndrome, it's a oncologic complication potentially deadly if the prophylactic treatment its avoided. Cases of acute lymphoblastic leukemia associated with pregnancy has been poorly documented in the literature the association of these two entities to pregnancy is the first report published worldwide, so the information is limited.

Acute kidney injury in adults with hemophagocytic lymphohistiocytosis.

BACKGROUND: Acute kidney injury (AKI) in the setting of hemophagocytic lymphohistiocytosis (HLH) is poorly characterized. This study aims to describe the incidence, clinical and biological features, and outcome associated with AKI in this population. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients with secondary HLH admitted to a single center from February 2007 through January 2013. 95 patients were included in the study. PREDICTOR: AKI. OUTCOMES: Recovery of kidney function, 6-month mortality, and complete remission of the underlying disease. MEASUREMENTS: AKI was defined according to the KDIGO 2012 guideline. Recovery of kidney function was defined as improvement in serum creatinine level, with return to baseline serum creatinine level ±26.5µmol/L. RESULTS: HLH was related to hematologic malignancy in 73 (77%), infectious disease in 21 (22%), and autoimmune disease in 9 (10%) patients and was multifactorial in 10 (11%) patients. The cause was undetermined in 2 (2%) patients. The incidence of AKI during HLH is high (62%), and 59% of the AKI population required renal replacement therapy. Main causes of AKI were acute tubular necrosis (49%), hypoperfusion (46%), tumor lysis syndrome (29%), or HLH-associated glomerulopathies (17%). At 6 months, 32% of the patients with AKI had chronic kidney disease. Two factors were associated independently with 6-month mortality by multivariable analysis: AKI stage ≥ 2 (OR, 2.61; 95% CI, 1.08-6.29; P=0.03) and an underlying hematologic malignancy (OR, 3.1; 95% CI, 1.05-9.14; P=0.04). In patients with hematologic malignancy, AKI was associated with lower 6-month complete remission (non-AKI, 25%; AKI patients, 5%; P=0.05). LIMITATIONS: Retrospective study, lack of histologic data. CONCLUSIONS: AKI in patients with HLH is frequent and adversely affects remission and survival. Early intensive management, including administration of etoposide, nephrotoxic drug withdrawal, prevention of tumor lysis syndrome, or aggressive supportive care, might improve kidney function and survival.

Rapid progression of anemia related to tumor-lysis syndrome associated with bortezomib treatment in myeloma patients.

OBJECTIVE: Tumor-lysis syndrome is a rare complication in patients with multiple myeloma. However, bortezomib treatment for myeloma is often associated with tumor-lysis syndrome. METHODS: We developed an index called the rapid anemia progression index, which represents the duration and progression of anemia, to evaluate risk factors for tumor-lysis syndrome. We retrospectively reviewed 35 relapsed or refractory myeloma patients treated with bortezomib-containing treatment in our institution. We analyzed various parameters, including albumin, lactase dehydrogenase, ß2-microglobulin and creatinine, similar to the rapid anemia progression index, and evaluated the risk factors for tumor-lysis syndrome associated with bortezomib by the Cairo-Bishop definition. RESULTS: Clinical tumor-lysis syndrome occurred in six patients (17.1%). Tumor-lysis syndrome occurred during the first course of bortezomib-containing treatment among all the patients. The result of the area under the receiver operating characteristic curve for the rapid anemia progression index was 0.759 (P = 0.049). The rapid anemia progression index was more accurate than the index of lactate dehydrogenase, ß2-microglobulin, albumin and creatinine according to the receiver operating characteristic curve. For a cut-off point of -1.12 for the rapid anemia progression index, the sensitivity and specificity were 66.7 and 82.8%, respectively. CONCLUSIONS: The rapid anemia progression index is related to clinical tumor-lysis syndrome associated with bortezomib treatment for multiple myeloma patients with a cut-off point of -1.12 g/dl/month.

Hyperuricemia and acute kidney injury secondary to spontaneous tumor lysis syndrome in low risk myelodysplastic syndrome.

BACKGROUND: This is a rare instance of acute kidney injury caused by hyperuricemia due to spontaneous tumor lysis syndrome and also the first case of spontaneous tumor lysis syndrome reported in association with myelodysplastic syndrome. CASE PRESENTATION: A 53-year-old man presented with abrupt oliguria. Laboratory findings on admission included hyperuricemia, hyperphosphatemia, hypocalcemia, metabolic acidosis and rapidly rising serum creatinine, which were consistent with acute tumor lysis syndrome in the absence of precipitating chemotherapy or radiotherapy. After hemodialysis and oral uric acid lowering therapy, serum uric acid levels returned to normal range and renal function rapidly recovered. The patient was diagnosed as myelodysplastic syndrome eleven months later. CONCLUSIONS: Occult malignancy including solid tumors and hematological malignancies should be carefully evaluated in the case of unexplainable acute kidney injury with hyperuricemia. Aggressive investigations should be thoroughly considered and repeated in this population.

What is the incidence of kidney stones after chemotherapy in patients with lymphoproliferative or myeloproliferative disorders?

INTRODUCTION: This study describes the incidence and risk factors of de novo nephrolithiasis among patients with lymphoproliferative or myeloproliferative diseases who have undergone chemotherapy. MATERIALS AND METHODS: From 2001 to 2011, patients with lymphoproliferative or myeloproliferative disorders treated with chemotherapy were retrospectively identified. The incidence of image proven nephrolithiasis after chemotherapy was determined. Demographic and clinical variables were recorded. Patients with a history of nephrolithiasis prior to chemotherapy were excluded. The primary outcome was incidence of nephrolithiasis, and secondary outcomes were risk factors predictive of de novo stone. Comparative statistics were used to compare demographic and disease specific variables for patients who developed de novo stones versus those who did not. RESULTS: A total of 1,316 patients were identified and the incidence of de novo nephrolithiasis was 5.5% (72/1316; symptomatic stones 1.8% 24/1316). Among patients with nephrolithiasis, 72.2% had lymphoproliferative disorders, 27.8% had myeloproliferative disorders, and 25% utilized allopurinol. The median urinary pH was 5.5, and the mean serum uric acid, calcium, potassium and phosphorus levels were 7.5, 9.6, 4.3, and 3.8 mg/dL, respectively. In univariate analysis, mean uric acid (p=0.013), calcium (p<0.001)), and potassium (p=0.039) levels were higher in stone formers. Diabetes mellitus (p<0.001), hypertension (p=0.003), and hyperlipidemia (p<0.001) were more common in stone formers. In multivariate analysis, diabetes mellitus, hyperuricemia, and hypercalcemia predicted stone. CONCLUSIONS: We report the incidence of de novo nephrolithiasis in patients who have undergone chemotherapy. Diabetes mellitus, hyperuricemia, and hypercalcemia are patient-specific risk factors that increase the odds of developing an upper tract stone following chemotherapy.

[The specific features of renal lesion in Burkitt's lymphoma].

AIM: To analyze the causes of renal lesion in patients with Burkitt's lymphoma (BL) and to develop optimal treatment policy. MATERIALS AND METHODS: The data of examination and treatment were analyzed in 20 patients with BL (14 men and 6 women aged 15 to 57 years (median age 24 years)) who had been followed up for renal lesion at the Hematology Research Center (HRC) in 2003 to 2011. When admitted to hospital, all the patients were found to have ureteric compression, renal parenchymal tumor infiltration, massive tumor cytolysis syndrome (MTCS). Polychemotherapy (PCT) was performed in accordance with the original intensive BL-M-04 protocol. The extent of the process was estimated according to the classification developed by S.B.Murphy: L3 variant B of acute lymphoblastic leukemia in 10 cases; Stage IV in 2; Stage III in 8. Acute renal failure (ARF) was identified in 13 patients. A control group comprised 36 patients with BL without ARF who had been followed up at the HRC in 2003 to 2011 and included into the BL-M-04 protocol. The ratio of patients with bone marrow lesion was 7:13 and 9:36 in the BL + ARF and BL-ARF groups, respectively. RESULTS: Decreased urine specific gravity and proteinuria (0.4 to 1.3 g/l) were the first manifestations of renal lesion and were seen in approximately 50% of all cases both on admission to hospital and in the first stages of PCT (10 and 9, 8 and 7 of the 20 cases, respectively). Microhematuria more commonly developed after initiation of PCT (7 and 3 of the 20 cases, respectively). ARF was diagnosed in 13 patients (24% of the 55 BL patients followed up at HRC in 2003 to 2011). One female patient developed ARF after the start of PCT. Twelve patients developed this condition at the onset of disease; in 4 patients, ARF existing prior to PCT began progressing after drug administration. The etiology of ARF was generally mixed. At the onset of disease, MTCS (n = 6) and specific renal parenchymal infiltration (n=6) were more common causes of ARF. Postrenal anuria was present in 2 cases. ARF after PCT initiation resulted from the toxic effects of methotrexate and MTCS (3 and 4 cases, respectively). ARF regressed in the early periods: in the prophase (n = 4) and during or the first PCT block A (n = 9). The BL patients with ARF, as compared to those without the latter, showed a statistically significant earlier onset of myelotoxic agranulocytosis (MTA): on day 3 of an intercourse interval (95 CI from 0 to 3 days) versus its day 5 (95% CI from 2 to 5 days) and a statistically significant longer duration of MTA--12 days (95% CI from 7 to 16 days) versus 7 days (95% Cl from 3 to 10 days); they were observed to have more severe mucositis. Despite the longer intercourse interval, 10 patients with ARF achieved remission; 4 patients died from therapy-refractory sepsis and 1 patient from thrombocytopenia. In the patients with ARF, mortality rates were significantly higher than in those without ARF (33% versus 10%; p = 0.04). CONCLUSION: Although there is a high risk of worsening renal dysfunction, PCT is a necessary condition for ARF resolution in BL.

Serum phosphate level and its kinetic as an early marker of acute kidney injury in tumor lysis syndrome.

INTRODUCTION: Acute kidney injury (AKI) is a major cause of mortality in tumor lysis syndrome. The biochemical parameters and kinetics of tumor lysis syndrome remain poorly described. Particularly, whether blood serum phosphate variations may help in the identification and management of patients who will eventually develop AKI remains to be studied. METHODS: In this retrospective study, we included patients with tumor lysis syndrome episodes without AKI at diagnosis, and analyzed serum phosphate kinetic, clinical and tumor lysis syndrome biochemical variables to identify factors associated with AKI onset, and determine threshold values of phosphatemia associated with AKI development. RESULTS: One hundred thirty tumor lysis syndrome episodes occurred in 120 patients during an 11-year period at the University Hospital of Angers. AKI developed in 56 tumor lysis syndrome episodes. In multivariable analysis, among the analyzed factors, only an increase in serum phosphate levels (before AKI diagnosis), exposure to platinum salts and an increase in LDH levels were associated with AKI development. Before AKI onset, a serum phosphate cut-off of 2.1 mmol/L was not effective in predicting AKI development (sensitivity 48%, specificity 84%, area under the receiver operating characteristic curve (AUC) 0.63 [0.52-0.74]). No other biochemical parameters were effective to better predict AKI occurrence. CONCLUSION: This work suggests that increases in serum phosphate and LDH appear to be early and reliable biomarkers of AKI in tumor lysis syndrome. No valuable threshold value of serum phosphate was found to effectively predict AKI. This work is the basis for further prospective controlled studies on phosphate monitoring and phosphate lowering therapies to prevent AKI during tumor lysis syndrome.

Rescue Therapies for AKI in Onconephrology: Rasburicase and Glucarpidase.

Tumor lysis syndrome (TLS) and high-dose methotrexate (HD MTX) toxicity can present with potentially severe complications, including acute kidney injury, in patients with malignancy. Guidelines for using rasburicase and glucarpidase as rescue therapies for TLS and HD MTX toxicity, respectively, are widely used by clinicians intending to mitigate organ toxicity and decrease morbidity and mortality as a consequence of cancer therapy. This review discusses the pathogenesis of TLS and HD MTX-associated toxicity, to understand the mechanism of action of these therapeutic agents and to review the currently available evidence supporting their use.

Survey of Anaphylaxis during Rasburicase Re-Administration in Patients with Hematological Malignancies Using a Japanese Claims Database.

Management of tumor lysis syndrome (TLS) associated with cancer chemotherapy for malignant tumors is important because of its potentially fatal course. The use of rasburicase, a recombinant urate oxidase, is recommended for TLS; however, because rasburicase is an enzymatic drug, one should be cautious of anaphylaxis during administration. Using claims data in Japan, we investigated the rate of rasburicase re-administration and the occurrence of anaphylaxis during re-administration in patients with hematopoietic malignancies in a multicenter setting. Re-administration of rasburicase was defined as administration after an interval of 21 days from the first dose. Of 373 patients, 18 were re-administered rasburicase (re-administration rate: 4.8%). No patient developed anaphylaxis. The median number of days from the first to the last dose of rasburicase was 256.5 days (interquartile range: 138.8-455.8 days). The median daily dose was 7.5 mg (4.5-11.3 mg), and the median total dose was 33.8 mg (19.1-64.1 mg). This claims database analysis revealed that the re-administration rate of rasburicase was low in Japanese patients with hematopoietic malignancies, suggesting that rasburicase was being used appropriately, and that associated anaphylaxis was not observed.