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.     

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.     

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.     

Tumor lysis syndrome following docetaxel therapy for extensive metastatic prostate cancer

Tumor Lysis Syndrome (TLS) is characterized by biochemical changes due to rapid tumor lysis of malignant cells, usually after chemotherapy. Typically it is seen in patients with hematologic malignancies sensitive to chemotherapy within days of receiving chemotherapy. Recently Baeksgaard and Sorensen reviewed the small number of cases of TLS after treatment of nonhematologic malignancies reported between 1977 and 2002. After careful review of the literature, I describe what appears to be to the first reported case of TLS associated with chemotherapeutic treatment of metastatic prostate cancer.     

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.     

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.     

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.     

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.     

Non-Hodgkin's lymphoma in the elderly. Part 2: treatment of diffuse aggressive lymphomas

As noted in part 1 of this two-part article, non-Hodgkin's lymphoma is one of a few malignancies that have been increasing in incidence over the past several decades. Likewise, these disorders are more common in elderly patients, with a median age of occurrence of 65 years. Therapy in elderly patients may be affected by multiple factors, especially attendent comorbidities. The approaches to management of these patients, with either indolent or aggressive disease processes, have been based on prospective clinical trial results, many of which have included a younger patient population. Fortunately over the past decade, results of treatment trials that have targeted an older patient population have emerged. The disease incidence and treatment approaches for both follicular (part 1) and diffuse aggressive (part 2) histologies in elderly patients are reviewed, as well as the impact of aging on the care of these patients.     

Non-Hodgkin's lymphoma in the elderly. Part 1: Overview and treatment of follicular lymphoma

Non-Hodgkin's lymphoma is one of a few malignancies that have been increasing in incidence over the past several decades. Likewise, these disorders are more common in elderly patients, with a median age of occurrence of 65 years. Therapy in elderly patients may be affected by multiple factors, especially attendant comorbidities. The approaches to management of these patients, with either indolent or aggressive disease processes, have been based on prospective clinical trial results, many of which have included a younger patient population. Fortunately, over the past decade, results of treatment trials that have targeted an older patient population have emerged. The disease incidence and treatment approaches for both follicular (part 1 of this article) and diffuse aggressive (part 2) histologies in elderly patients are reviewed, as well as the impact of aging on the care of these patients.     

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。     

Extensive chromosomal breaks are induced by tamoxifen and estrogen in DNA repair-deficient cells

Tamoxifen (TAM) possesses antiestrogen activity and is widely used for the treatment or prevention of breast cancer. However, it is also carcinogenic in human uterus and rat liver, highlighting the profound complexity of its actions. To explore the molecular mechanisms of TAM-induced mutagenesis, we analyzed the effects of this drug on gene-disrupted chicken B lymphocyte (DT40) clones deficient in various DNA repair pathways. Rad18, Rev3, and Polkappa are involved in translesion DNA synthesis (TLS), which facilitates recovery from replication blocks on damaged template strands. DT40 cells deficient in TLS were found to be hypersensitive to TAM, exhibiting an increase in chromosomal breaks. Furthermore, these mutants were also hypersensitive to 4-hydroxyestradiol, a physiological metabolite of estrogen. These data suggest a contribution of TLS to the prevention of chromosomal breaks by TAM and estrogen, and they therefore indicate that such error-prone DNA synthesis underlies mutagenesis induced by these agents.     

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.     

Equal Treatment and Outcomes for Everyone with Multiple Myeloma: Are We There Yet?

Multiple myeloma treatment has changed tremendously over recent years leading to overall improvement in patient outcomes. With therapeutic advancements, patient care has become increasingly complex and variability is seen in healthcare delivery as well as outcomes when various patient subgroups are analyzed based on sociodemographic factors. It is imperative to understand this variability so that while overall the outcomes get better, specific focus is placed on subgroups that may remain disadvantaged and may not be able to fully access the advancements in therapeutics. Research in multiple myeloma has specifically looked at several such patient subgroups based on socioeconomic status, age, race/ethnicity, insurance carrier, and geographic location that may affect healthcare utilization and patient outcomes. Exploring and understanding these would certainly help address disparities and lead to further equity in healthcare access and, hopefully, patient outcomes.     

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     

The Role of the Taxanes in the Treatment of Older Patients with Advanced Stage Non‐Small Cell Lung Cancer

The treatment of older patients with advanced non‐small cell lung cancer (NSCLC) represents a considerable challenge for physicians. A patient 's suitability for chemotherapy is frequently based solely on chronologic age; as a consequence, older patients with NSCLC are less likely to receive standard chemotherapy than younger patients. Although age‐related factors, such as comorbid illness, should be taken into consideration when assessing a patient 's suitability for treatment, fit and functionally independent older patients should be considered candidates for standard chemotherapy. The taxanes are widely used in the treatment of advanced‐stage NSCLC and are well tolerated in older patients. The efficacy of both paclitaxel and docetaxel has been studied in older patients and appears to be comparable with that seen in younger patients either as monotherapy or in combination with a platinum compound as first‐line therapy. In addition to the available evidence, prospective evaluation of novel agents in elderly‐specific or ‐enriched studies is necessary to guide the treatment of older patients with NSCLC.     

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.     

Prognostic factors in breast cancer

A variety of tumor characteristics can provide prognostic information useful in managing the patient with primary breast cancer. Some of these characteristics are firmly established, whereas others are observer dependent or require prospective validation. No single characteristic, however, is likely to fully define which patient with primary breast cancer is destined to relapse. This clinical dilemma--recognition of the high-risk patient--is particularly important in the management of women with node-negative breast cancer. Because most women with this early stage of disease will be cured by surgery alone, the use of adjuvant chemotherapy must be limited to high-risk subsets. Tumor size and ER status are established prognostic factors. Histologic and nuclear grade may be important, but problems of interobserver variability remain. Some studies have shown that aneuploidy or a high S-phase fraction may be independent, high-risk characteristics. Flow cytometric DNA content analysis must be applied with caution, however, because the calculation of S-phase fraction has not been standardized and because the prognostic utility of this approach has not been prospectively confirmed. For now, a prudent approach might be to gather as much prognostic information about each patient's tumor as possible. Those with several of the high-risk characteristics listed in Table 2 should receive strongest consideration for adjuvant treatment. Some of these same prognostic factors, along with several others, can be used to characterize the high-risk node-positive patient. The number of involved axillary nodes is the most important established predictor. Progesterone-receptor status is associated with both disease-free and overall survival, whereas ER status is independently related only to overall survival. Histologic grade, DNA ploidy, and S-phase fraction can also be used to help define the high-risk patient. Finally, tumors that amplify or overexpress the HER-2 gene may have a higher risk of relapse, although this finding has been questioned. Management of patients with breast cancer requires an individualized approach that is based on a careful weighing of a variety of prognostic considerations. The relative importance of these factors will require further large-scale, prospective, multiparameter studies. Although results from such studies are awaited, an understanding of the clinical heterogeneity of breast cancer must be based on a multiplicity of observations, each of which characterizes, in a limited way, the biology of this disease.     

Urate Nephropathy from Tumor Lysis Syndrome in an Undiagnosed Case of Prostate Cancer

Prostate cancer can masquerade as just normocytic anemia and thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or tumor lysis syndrome (TLS). We are reporting an intriguing case of metastatic prostate cancer which remained undiagnosed until the patient showed signs of tumor lysis syndrome (TLS), leading to urate nephropathy requiring urgent hemodialysis. Tumor lysis syndrome is an oncological emergency but an exceedingly rare complication in non-hematological malignancies, including prostate cancer. It is challenging to recognize features of TLS in a case such as this with an unknown diagnosis. In the case of an established diagnosis of malignancy, however, checking baseline renal function, uric acid, lactate dehydrogenase (LDH), potassium, and phosphate to monitor for TLS as well as considering urate lowering therapy can help prevent adverse outcomes.