实体瘤溶解综合征

肿瘤溶解综合征是血液系统肿瘤治疗中常见的并发症,但在实体瘤中较少见,其发病隐匿,极易误诊、漏诊,预后差.实体瘤溶解综合征典型的临床特征为高尿酸血症、高钾血症、高磷血症和低钙血症,并发症主要为急性肾功能衰竭和心律失常.对高危患者进行预防性干预、早期诊断和积极治疗是改善预后的关键.本文回顾既往文献报道的87例实体瘤溶解综合征,对其发病情况、预防和治疗进行综述.     

Recombinant urate oxidase for prevention of hyperuricemia and tumor lysis syndrome in lymphoid malignancies

Hyperuricemia is a common manifestation of lymphoid malignancies at diagnosis or after the start of chemotherapy. When accompanied by other metabolic abnormalities and/or organ failure, hyperuricemia may be a manifestation of tumor lysis syndrome (TLS). Patients at particularly high risk of such complications include those with acute lymphoblastic leukemia and advanced stage non-Hodgkin's lymphoma. Conventional measures to prevent hyperuricemia and TLS are comprised of hydration, alkalinization of body fluids, and administration of allopurinol. Although these measures are usually effective in preventing or managing hyperuricemia, approximately 20% of patients at high risk of TLS require dialysis, and many cannot receive chemotherapy as planned. Rasburicase, a recombinant form of the enzyme urate oxidase, has recently become available and may further reduce the morbidity of hyperuricemia and TLS. In this review, we provide an overview of hyperuricemia and TLS and discuss the impact of rasburicase in the overall management of these complications.     

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.     

Tumor lysis syndrome and metastatic melanoma

Tumor lysis syndrome (TLS) is a potential emergent complication of oncologic treatment. TLS is commonly reported in hematological malignancies with rapid cell turnover rates, but is relatively rare in solid tumors. TLS is most frequently a result of cancer treatment in combination with a large tumor burden, but has occasionally been reported to occur spontaneously, especially in cases of advanced or metastatic disease. In this article, we describe the case of a patient with newly diagnosed metastatic melanoma that developed TLS two days after initiation of corticosteroids. In addition, we present a brief literature review of melanoma-associated TLS and review the etiology, diagnosis, and management of TLS.     

Spontaneous tumor lysis syndrome in acute myeloid leukemia: two cases and a review of the literature

Spontaneous tumor lysis syndrome (TLS) is a constellation of electrolyte abnormalities and acute renal failure, which occurs in the setting of rapid cell turnover prior to the administration of cytotoxic chemotherapy. While spontaneous TLS is well described in patients with Burkitt's lymphoma, it is thought to occur less commonly in other hematologic malignancies. We present two cases of spontaneous TLS in patients with newly diagnosed acute myeloid leukemia (AML) followed by a review of the literature in this field.     

Tumour Lysis Syndrome: Implications for Cancer Therapy

The tumour lysis syndrome (TLS) is a group of metabolic abnormalities caused by rapid and unexpected releaseof cellular components into the circulation as a result of massive destruction of rapidly proliferating malignantcells. It usually develops in patients with hematologic malignancies like acute lymphoid leukemia, non-Hodgkinand Burkitt’s lymphoma after initiation of chemotherapy or may, rarely, occur spontaneously. Though TLS isseldom observed in relation to solid tumours, there have been reports of connections with examples such aslung, liver, breast, gastric carcinomas. The clinical manifestations of TLS include hyperuricemia, hyperkalemia,hyperphosphatemia and hypocalcemia. These indications if untreated lead to life-threatening complications suchas acute renal failure, cardiac arrhythmias, seizures, and eventually death due to multiorgan failure. Thereforeearly detection of TLS is of vital importance. This can be accomplished by identification of high risk patients,implementation of suitable prophylactic measures andmonitoring of the electrolyte levels in patients undergoingchemotherapy.     

肿瘤溶解综合征11例报告

目的：探讨肿瘤溶解综合征发生的危险因素及其治疗。方法：对11例化疗早期发生肿瘤溶解综合征的肿瘤患者临床特点及化疗前后各项实验生化指标进行分析。结果：初次治疗、男性、年轻、肿瘤负荷高、化疗前有肾功能不全、血尿酸水平高、血乳酸脱氢酶高、存在脱水和酸性尿等为发生肿瘤溶解综合征的危险因素。结论：对存在发生肿瘤溶解综合征的危险因素的患者，必须高度重视和早期采取发适当治疗措施。     

Tumor lysis syndrome following hemi-body irradiation for metastatic breast cancer

Tumor lysis syndrome (TLS) is a rare serious acute complication of cancertherapy, reported mainly following chemotherapy in patients with large tumorload and chemosensitive disease. These are mainly patients with non-Hodgkin'slymphoma, leukemia and rarely in solid tumors. It is less frequently describedafter radiotherapy for lymphoid and hematological malignancies. TLS followingradiotherapy for solid tumors is a very rare complication. In thisreport/review we describe a seventy-three-year-old male patient withprogressive metastatic carcinoma of the breast to the lungs, liver and bone.He was referred for radiotherapy because of generalized bony pains. Thepatient was planned for sequential hemi-body irradiation starting with themore symptomatic upper half body. After premedication, he was given 8.5 Gy tothe mid point at the maximum chest separation with anterior lung attenuatorlimiting uncorrected lung dose to 6.15 Gy. A further 3.5 Gy electron boost tothe fungating breast tumor was given to the 100%.Forty-eight hours after irradiation he developed hyperkalemia,hyperphosphatemia, hyperuricemia, hypocalcemia and renal failure. Theseclinical and biochemical changes are typical of tumor lysis syndrome (TLS).Despite hydration, and treating the hyperuricemia, the patient developed comaand died eight days after irradiation.The prophylaxis and management of TLS and in high-risk patients aredescribed to avoid this frequently fatal complication.     

A predictive model for the detection of tumor lysis syndrome during AML induction therapy

Tumor lysis syndrome (TLS) is defined by metabolic derangements occurring in the setting of rapid tumor destruction. In acute myelogenous leukemia (AML), TLS frequency, risk stratification, monitoring, and management strategies are based largely on case series and data from other malignancies. A single-center, retrospective cohort study was conducted to estimate TLS incidence and identify TLS predictive factors in a patient population undergoing myeloid leukemia induction chemotherapy. This study included 194 patients, aged 18-86 years, with AML or advanced myelodysplastic syndrome undergoing primary myeloid leukemia induction chemotherapy. Nineteen patients (9.8%) developed TLS. In univariate analysis, elevated pre-chemotherapy values for uric acid (P < 0.0001), creatinine (P = 0.0025), lactate dehydrogenase (LDH) (P = 0.0001), white blood cell (P = 0.0058), gender (P = 0.0064) and chronic myelomonocytic leukemia history (P = 0.0292) were significant predictors. In multivariate analysis, LDH (P = 0.0042), uric acid (P < 0.0001) and gender (P = 0.0073) remained significant TLS predictors. A predictive model was then designed using a scoring system based on these factors. This analysis may lay the groundwork for the development of the first evidence-based guidelines for TLS monitoring and management in this patient population.     

Effectiveness of Single-dose Rasburicase in Patients With Lymphoid Malignancies at a High Risk for Tumor Lysis Syndrome

BackgroundTumor lysis syndrome (TLS) is a life-threatening disorder that occurs mainly in patients with high-tumor burden hemato-oncologic malignancies. It results in metabolic derangements, including hyperuricemia and acute renal failure. The powerful management for TLS is a daily dose of rasburicase for up to 5 days before chemotherapy; however, the optimal dose and duration of rasburicase for TLS prophylaxis have not been standardized for patients at high risk for TLS. Therefore, we evaluated the efficacy of single-dose rasburicase for prophylactic purposes in patients with malignant lymphoma at high risk for TLS.Patients and MaterialsWe retrospectively evaluated patients with malignant lymphoma at high risk for TLS treated with a prophylactic single-dose of rasburicase (0.1-0.2 mg/kg) from March 2012 to March 2016.ResultsA total of 67 patients treated with a single-dose of rasburicase for prophylaxis were analyzed. A relatively large number of patients (n = 23; 34.3%) had the highly proliferative lymphoblastic lymphoma subtype (n = 14) or Burkitt lymphoma (n = 9) and were at the highest risks of tumor lysis. Two patients were newly diagnosed with TLS; the incidence of TLS after single-dose prophylaxis was 3.0%. Multivariate analysis revealed no predictable risk factors for response to prophylactic rasburicase, though increased level of serum creatinine approached statistical significance in reducing the efficacy of single-dose rasburicase to prevent TLS (odds ratio, 3.61; P = .054).ConclusionOur data indicated that single-dose rasburicase effectively prevented progression of TLS, and, regardless of any risk factors, including increased creatinine, single-dose rasburicase for TLS prophylaxis was useful in patients with lymphoma at a high risk for TLS.     

Spontaneous tumor lysis syndrome in a patient with cholangiocarcinoma

Tumor lysis syndrome (TLS) is a potentially deadly complication of tumors or their treatment. This syndrome consists of a constellation of laboratory parameters such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia and clinical complications such as seizures, acute renal insult, cardiac dysrhythmias and death. TLS is especially common in patients with hematological malignancies with rapid cellular turnover rates such as acute lymphocytic leukemia and Burkitt lymphoma, but is very rare in patients with solid tumors. However, it is essential to keep in mind that solid tumors can also lead to TLS. We present a case of a 66-year-old African American male with metastatic cholangiocarcinoma complicated by the development of spontaneous TLS. TLS has never been reported in a patient with cholangiocarcinoma.     

Acute tumor lysis syndrome in a hemodialysis patient with diffuse large B cell lymphoma

Acute tumor lysis syndrome (TLS) is a life-threatening complication of cancer therapy requiring prompt recognition and aggressive management. It occurs particularly in patients with lymphoproliferative disease during potent myelosuppressive therapy. To our knowledge, acute TLS in end-stage renal disease (ESRD) patients with malignancy is extremely rare and has never been reported in English literature. We report the first case of acute TLS in an ESRD woman with diffuse large B cell lymphoma after chemotherapy. Aggressive treatments with daily hemodialysis and allopurinol rather than hydration benefit the patient. There is neither optimal therapy in treating ESRD patients with TLS nor adequate guidelines for how to adjust the chemotherapy drug in hemodialysis patients. This case provides our experience to clinician how to treat acute TLS in ESRD patients.     

Acute tumor lysis syndrome in solid tumors—a case report and review of the literature

PURPOSE: Tumor lysis syndrome (TLS) is a potential complication in cancer therapy. It may occur in highly sensitive tumors, especially in childhood cancers and acute leukemias, whereas it is rare in the treatment of adult solid tumors. TLS is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia following massive lysis of malignant cells. Complications include acute renal failure and metabolic acidosis. We report the first case of TLS during chemotherapy in a patient with metastatic medulloblastoma, together with a review of the literature regarding the occurrence of TLS in patients with solid tumors. METHODS: Data regarding clinical and biochemical parameters were extracted from the actual patients' files. Reports of TLS in the English language literature up to 2002 were identified by searching Medline. RESULTS: A 23-year old male with metastatic medulloblastoma received chemotherapy with cisplatin and etoposide due to massive extracerebral manifestations including metastases to the liver, mediastinal lymph nodes and bone marrow metastases. The patient developed classical signs of TLS on the second day of chemotherapy, including acute renal failure. A 17-fold increase in plasma LDH up to 87608 U/l was observed together with a 4-fold increase in plasma creatinine. The patient was treated with aggressive hydration, allopurinol and repeated hemodialysis. During the following days the patient improved and the biochemical markers all returned to normal. REVIEW. Reviewing the literature, a total of 45 patients with solid tumors who developed TLS have been reported. Most of the patients presented with metastatic, therapy-sensitive disease. Although preventable in practically 100% of patients, TLS is a potentially fatal complication, and in this material the mortality rate was one in three. Risk factors included increased LDH, hyperuricemia and pretreatment azotemia. CONCLUSIONS: TLS is only rarely associated with treatment of solid tumors. Precautions should be taken to avoid this potentially fatal complication in (chemo)therapy of solid tumors, especially in therapy-sensitive tumors presenting with bulky, metastatic disease and preexisting risk factors, including azotemia, elevated LDH and hyperuricemia. Prophylactic treatment to avoid TLS includes allopurinol, hydration prior to treatment and alkalization of the urine. Urate oxidase (rasburicase) is now beginning to replace allopurinol as a more effective way of reducing hyperuricemia and thereby the risk of TLS.     

Tumour lysis syndrome in solid tumours

Tumour lysis syndrome (TLS) is an oncological emergency that results from massive cytolysis of malignant cells with a sudden release of their cellular contents, such as intracellular ions and metabolic by-products, into the systemic circulation. This syndrome is common in tumours with rapid cell turnover and growth rates, and in bulky tumours with high sensitivity to antineoplastic treatments. It is, therefore, a well-recognised clinical problem in haematological malignancies. It is rarely observed in solid tumours. Here, published studies are reviewed, beginning with the first report of TLS in solid tumours. Reported solid TLS cases are evaluated according to their common features and differences, and their similarities with those seen in haematological malignancies. Basic principles for the prevention and management of TLS are mentioned, with particular emphasis on solid tumours.     

Maxillary Sinus Squamous Cell Carcinoma Presenting with Fatal Tumor Lysis Syndrome: A Case Report and Review of the Literature

Acute tumor lysis syndrome (TLS) is a condition resulting from rapid destruction of tumor cells and subsequent massive release of cellular breakdown products. It has been described following the treatment of many hematologic and solid malignancies. However, spontaneous TLS has rarely been described. Here we report a case of spontaneous TLS that occurred in a patient with a treated maxillary squamous cell carcinoma (SCC) presenting with diffuse liver metastases, which is an infrequent site of distant metastases.Key Words: Squamous cell carcinoma, Tumor lysis syndrome, Liver metastases, Maxillary sinus     

Fixed-Dose Recombinant Urate Oxidase in the Treatment of Paediatric Tumour Lysis Syndrome: A Regional Cancer Centre Experience

Background: Tumor lysis syndrome (TLS) is an oncologic emergency commonly seen in children with hemato-lymphoid malignancies. Recombinant urate oxidase (RUO) is used in both the prophylaxis and treatment of TLS. However, in resource-constrained countries, its role is mostly limited to the treatment of established TLS and data regarding the use of RUO and its outcome is sparse. Objective: To describe the outcome of Pediatric TLS following the use of a fixed – dose of RUO. Methods: A retrospective chart review of all children <15 years of age admitted in the Department of Paediatric Oncology, Kidwai Cancer Institute from April 2017 to July 2018 with TLS and treated with a single, fixed – dose (1.5 mg) RUO was undertaken. Results: During the study period, 255 children with hemato-lymphoid malignancies were diagnosed to be at risk of developing TLS. Of these, only 22 (8.6%) children developed TLS and received RUO. Among those with TLS, 15 (68.2%) had Acute Lymphoblastic Leukemia (ALL) while 7 (31.8%) had Non - Hodgkin lymphoma (NHL). 91% (20/22) children had spontaneous TLS and the remainder developed therapy-related TLS. Median age at presentation was 8 years (IQR 5.25,1.75) with 4.5:1 male: female ratio. The mean urate level at admission was 19.12 mg/dl (+/- 8mg/dl) (Range: 10.7–34.5). 91% (20/22) children received RUO at less than 0.15 mg/kg and the median dose of RUO was 0.05 mg/kg (IQR 0.038-0.08). Of the 22 children with TLS, 2 children failed to achieve normal serum urate levels at 24 hours in response to a single fixed-dose of RUO and hence received an extra dose of RUO. Serum urate levels remarkably declined following RUO administration from 19.12 mg/dl (+/-8) to 8.2 mg/dl (+/-3.9), 3.99 mg/dl (+/-1.6) and 2.84 mg/dl (+/-1.3) at 12h, 24h and 48h respectively. AKI was present in 15 (68.2%) children. The median eGFR of the group at diagnosis was 49 ml/min/1.73m2 (IQR 26.3, 70). None of the children required hemodialysis. No significant adverse events occurred. Conclusion: Fixed-dose RUO can achieve rapid, adequate and sustained drop in serum urate levels in Paediatric TLS. It is a useful strategy for managing TLS in resource-constrained settings.     

急性淋巴细胞白血病并发肿瘤溶解综合征7例

目的 :探讨急性淋巴细胞白血病 (AL L )患者化疗后发生肿瘤溶解综合征 (TL S)的临床特征。方法 :对 7例化疗发生 TL S的 AL L患者进行各项生化指标的分析。结果 :TL S患者表现为高尿酸血症、高血钾、高血磷、低血钙 ,并有不同程度的肾功能损伤 ,其中 1例发生了急性肾功能不全。用别嘌呤醇及静脉碱化利尿后 ,6例短期内血生化指标恢复正常。1例死于心衰。结论 :早期诊断并及时给予别嘌呤醇及静脉碱化利尿是治疗 TL S的关键     

Rasburicase (recombinant urate oxidase) for the management of hyperuricemia in patients with cancer: report of an international compassionate use study

BACKGROUND: Hyperuricemia and tumor lysis syndrome (TLS) are serious complications that can occur during chemotherapy for hematologic malignancies, even if standard management procedures, including administration of allopurinol, are undertaken. Rasburicase, a recombinant urate oxidase that converts uric acid (UA) into the soluble compound allantoin, has been shown to control hyperuricemia faster and more reliably than allopurinol.(1) METHODS: A compassionate use trial, running from January 1999 to December 2001, provided access to rasburicase for patients in nine countries who were at risk for TLS during the initiation of chemotherapy. Of the 280 patients enrolled in the study, 278 received rasburicase and were included in the analysis. A total of 166 pediatric patients who had leukemia (approximately 74%), lymphoma (approximately 24%), or solid tumors (approximately 3%) were treated with rasburicase. One hundred twelve adults with either leukemia (68%) or lymphoma (30%) also were treated. Rasburicase (0.20 mg/kg) was administered intravenously once a day for 1 to 7 days, at the investigator's discretion. Two doses daily could be administered during the first 3 days. A response was defined as a reduction in UA level or maintenance of a UA level less than 7.5 mg/dL (or less than 6.5 mg/dL, for children age < 13 years). RESULTS: UA levels at 24-48 hours after administration of the last dose of rasburicase were available for 122 pediatric patients and 97 adult patients. The mean UA level in 29 hyperuricemic children decreased from 15.1 mg/dL to 0.4 mg/dL, whereas in 27 hyperuricemic adults, the mean level decreased from 14.2 mg/dL to 0.5 mg/dL. Prophylactic administration of rasburicase to prevent TLS during chemotherapy reduced UA levels from a mean of 4.4 mg/dL to 0.8 mg/dL in 93 nonhyperuricemic children and from 4.8 mg/dL to 0.4 mg/dL in 70 nonhyperuricemic adults (for all reductions in UA levels, P < 0.001). The response rate was 100%. Rasburicase was very well tolerated. Serious adverse events related to rasburicase were observed in one patient. CONCLUSIONS: The results of the current study confirm that rasburicase is safe and highly effective in the prevention and treatment of chemotherapy-induced hyperuricemia in both children and adults.     

FLORENCE: a randomized,double-blind,phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk

BackgroundSerum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention.Patients and methodsPatients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7–9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA_1–8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety.ResultsA total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA_1–8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms.ConclusionIn the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile.Clinical trial registrationNCT01724528.