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.     

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.     

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.     

How we treat tumor lysis syndrome

Tumor lysis syndrome (TLS) is an oncology emergency that occurs as a result of rapid tumor cell breakdown and the consequent release of massive amounts of intracellular contents, including potassium, phosphate, and uric acid, into the systemic circulation. These metabolic disturbances lead to life-threatening conditions and may cause sudden death if not treated. TLS commonly occurs following initiation of cytotoxic treatment in patients with high-grade lymphomas or acute lymphoblastic leukemia. Spontaneous cases involving both solid and hematologic tumors have also been reported. Rarely, TLS occurs following treatment with irradiation, corticosteroids, hormonal therapy, or biologic therapy. It is necessary to identify patients at risk for TLS early in order to initiate preventive measures. In the event that preventive measures fail, the clinical parameters and signs of TLS must be understood and recognized so that treatment can begin as soon as possible, as this condition is a significant cause of morbidity and mortality.     

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.     

Tumor lysis syndrome after treatment with gemcitabine for metastatic transitional cell carcinoma

Tumor lysis syndrome is a set of life threatening complication that can arise from treatment of high tumor burden, drug sensitive, and rapidly proliferating neoplasm particularly of hematological origin. It is rarely described in patients with solid tumors. We report the first case of tumor lysis syndrome in a man with metastatic renal pelvic transitional cell carcinoma after gemcitabine treatment. Despite aggressive therapy, he died 2 weeks after TLS was diagnosed. Our experience demonstrates that administration of gemcitabine for metastatic renal pelvic transitional cell carcinoma may induce acute tumor lysis syndrome, which necessitates frequent laboratory monitoring and prompt initiation of appropriate therapeutic measures.     

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.     

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.     

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.     

In‐Hospital Outcomes of Tumor Lysis Syndrome: A Population‐Based Study Using the National Inpatient Sample

The epidemiology and outcomes of tumor lysis syndrome (TLS) are understudied. We used the National Inpatient Sample (NIS), a nationally representative weighted sample of all U.S. hospital discharges, to study outcomes and predictors of mortality in hospitalized patients with TLS. The NIS was queried for patients with a discharge diagnosis of TLS (ICD‐9 code 277.88) from 2010–2013. Baseline characteristics and outcomes were analyzed. A multivariable logistic regression analysis was performed to identify predictors of mortality. From 2010–2013, 28,370 patients were discharged with a diagnosis of TLS. The most common malignancies were non‐Hodgkin lymphoma (30%), solid tumors (20%), acute myeloid leukemia (19%), and acute lymphocytic leukemia (13%). Overall in‐hospital mortality was 21%. The median length of stay was 10 days (IQR 5‐22). Sixty‐nine percent of patients experienced a severe complication, including sepsis (22%, 95% confidence interval [CI] 21–23), dialysis (15%, 95% CI 14–16), acute respiratory failure (23%, 95% CI 22–24), mechanical ventilation (16%, 95% CI 15–17), gastrointestinal hemorrhage (6%, 95% CI 5–7), cerebral hemorrhage (2%, 95% CI 2–3), seizures (1%, 95% CI 0.6–1), and cardiac arrest (2%, 95% CI 2–3). Predictors of mortality were derived from a multivariable logistic regression and included age, Elixhauser comorbidity score, insurance status, teaching versus nonteaching hospital, and cancer type. Predictors of increased length of stay included age, race, teaching versus nonteaching hospital, and cancer type. In the U.S., many patients with TLS develop life‐threatening complications and a quarter die during hospitalization. As more cancer treatments become available, strategies to improve the supportive care of patients with TLS should be a priority.     

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.     

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.     

Incidence,medical resource utilisation and costs of hyperuricemia and tumour lysis syndrome in patients with acute leukaemia and non-Hodgkin's lymphoma in four European countries

Hyperuricemia (HU) and tumour lysis syndrome (TLS) are complications of acute leukaemia and non-Hodgkin lymphoma (NHL) leading to increased morbidity and mortality. The objective of this study was to define incidence and calculate health care cost associated with HU and TLS. 788 acute leukaemia and NHL patients from Belgium, The Netherlands, Spain and UK were screened retrospectively for HU and TLS. Resource use related to HU and TLS was recorded and costs were calculated applying local unit costs. Results showed that HU occurred in 18.9% of patients, and 27.8% of them fulfilled TLS criteria. The cost of HU without TLS was €672 (SE 181), the cost of TLS €7,342 (SE 1,412). TLS requiring dialysis incurred an average cost of €17,706. In conclusion, it is noted that the observed incidence rates were lower than earlier reports. In addition, some risk factors for HU and TLS (e.g. paediatric patients versus adults) were not associated with increased rates of HU or TLS as a consequence of higher rates of prevention. TLS cases incurred 11 times higher costs than HU cases in which TLS was absent. The main cost drivers in TLS are interventions requiring intensive care.     

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.     

Rapid tumor lysis syndrome in a patient with metastatic colon cancer as a complication of treatment with 5-fluorouracil/leucoverin and irinotecan

Tumor lysis syndrome is a potentially fatal complication of anti-cancer therapy that is usually seen in patients with bulky, rapidly proliferating, treatment-sensitive tumors such as hematological malignancies, but it rarely occurs in a variety of solid tumors such as colorectal carcinoma. Combination chemotherapy with infusional 5-fluorouracil/leucoverin and irinotecan has been recently accepted as the first treatment option for metastatic colorectal cancer. We present a case of tumor lysis syndrome in a patient with metastatic colon carcinoma that occurred 72 hrs after the initial course of a combination chemotherapy with irinotecan and 5-fluorouracil/leucoverin. Despite the immediate treatment with aggressive hydration by a sodium bicarbonate infusion, followed by forced diuresis and uricolytic therapy, he died of a sudden cardiac arrest complicated by acute renal failure. Our case indicates that administration of 5-fluorouracil/leucoverin and irinotecan for bulky tumors of colorectal origin with a rapid doubling time may induce an acute tumor lysis syndrome, which necessitates frequent laboratory monitoring and a close follow-up of the patient as well as prompt initiation of appropriate therapeutic measures.     

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     

Tumour lysis syndrome in children: experience of last decade

The strategy against tumour lysis syndrome (TLS) had been hyperhydration, urine alkalinization, and allopurinol. Recently, rasburicase was added to the armament against this life-threatening condition. In Korea, rasburicase is used as a rescue therapy for cases with allopurinol-resistant hyperuricemia, because of the restriction by the National Health Insurance. We reviewed our experiences to re-assess the risk factors of TLS and the efficacy of rasburicase. Medical records were retrospectively reviewed for 396 children who were diagnosed as positive with acute leukemia and non-Hodgkin lymphoma between the years 2000 and 2009. The risk factors for TLS were analyzed statistically, and those before and after the availability of rasburicase were compared. Sixty eight patients (17.2%) had TLS. Multivariate analysis showed that pre-chemotherapy hypophosphatemia was a risk factor for TLS, in addition to the known risk factors of hyperuricemia and high lactate dehydrogenase concentration. The availability of rasburicase as a rescue therapy did not negate the importance of uric acid as a risk factor of TLS. Rasburicase as a second line treatment for intractable hyperuricemia was not effective in reducing the incidence of TLS. Pre-chemotherapy hypophosphatemia was a significant independent risk factor for TLS.     

The management of tumor lysis syndrome

The manifestation of tumor lysis syndrome (TLS) occurs when the destruction of tumor cells releases breakdown products that overwhelm the excretory mechanisms of the body. A cardinal sign is hyperuricemia, leading to uric acid nephropathy. Other signs are hyperkalemia, hyperphosphatemia and secondary hypocalcemia. Conventional management of TLS consists of aggressive intravenous hydration, diuretic therapy, urinary alkalization, and inhibition of urate production by high-dose allopurinol. Urate oxidase has been used in the management of patients at risk for TLS and recently the recombinant urate oxidase rasburicase was developed. Several data indicate that rasburicase is effective and well tolerated in the prevention and treatment of chemotherapy-induced hyperuricemia. Treatment options of hyperkalemia include sodium polystyrene sulfonate, hypertonic glucose and insulin, loop diuretics, and bicarbonate. Treatment of hyperphosphatemia reduces dietary phosphate intake and includes phosphate binders such as aluminum hydroxide and aluminum carbonate. When recurrent hypocalcemia is present, a continuous intravenous infusion of calcium gluconate can be initiated. Hemodialysis should be considered for every patient with excessively elevated uric acid, phosphate and/or potassium and in those patients with acute renal failure to control urinary volume and manage uremia.     

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.     

儿童急性淋巴细胞白血病并发肿瘤溶解综合征18例临床分析

目的:探讨儿童急性淋巴细胞白血病（acute lymphoblastic leukemia,ALL）并发肿瘤溶解综合征（tumor lysis syndrome,TLS）的临床特点,分析TLS的危险因素以及预后。方法:回顾性收集2015年01月01日至2020年06月30日期间于我院就诊的253例ALL患儿的临床资料。分析TLS的危险因素以及TLS对ALL患儿预后的影响。结果:253例患儿中,18例（7.1%）患儿发生TLS,男女比例2.6∶1,中位年龄8.1岁。TLS患儿较非TLS患儿更容易出现窦性心动过速、前臂心肌复极异常以及QT间期延长（P<0.05）。初诊高白细胞计数（WBC≥50×109/L）与初诊非高白细胞TLS患儿的血尿酸、LDH、血肌酐、血钾、血校正钙及肌酐清除率（creatinine clearance,Ccr）之间没有统计学差异（P>0.05）。多因素分析显示初诊LDH≥900 U/L是TLS发生的独立危险因素。TLS组与非TLS组的EFS及OS没有统计学差异（P>0.05）。结论:初诊LDH≥900 U/L是TLS发生的独立危险因素。TLS并不影响ALL患儿的远期预后。