Transient myeloproliferative disorder is a hematologic abnormality characterized by an uncontrolled proliferation of myeloblasts in peripheral blood and bone marrow that primarily affects newborns and babies with Down syndrome. Tumor lysis syndrome is rarely associated with transient myeloproliferative disorder.
Transient myeloproliferative disorder was diagnosed in a seven-day-old baby girl with Down syndrome, who was referred to our department due to hyperleukocytosis. Our patient developed tumor lysis syndrome, successfully treated with rasburicase, as a complication of transient myeloproliferative disorder resulting from rapid degradation of myeloid blasts after initiation of effective chemotherapy.
Tumor lysis syndrome is rarely reported as a complication of transient myeloproliferative disorder. To the best of our knowledge, this is the first case of a newborn with Down syndrome and transient myeloproliferative disorder treated with rasburicase for developing tumor lysis syndrome.
Acute tumor lysis syndrome (TLS) occurs frequently in hematologic malignancies such as high-grade lymphomas and acute leukemia, which are rapidly proliferating and chemosensitive tumors. It occurs rarely in solid tumors and has never been reported in gastric adenocarcinoma. Typical biochemical findings of acute tumor lysis syndrome are hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia in patients with a malignancy. Rapid changes of these electrolytes may cause cardiac arrhythmia, seizure, acute renal failure and sudden death. Therefore, as soon as it is detected, it should be taken care of immediately. Until now almost all cases of TLS associated with solid tumor have developed after cytoreductive therapy in chemosensitive tumors. We report here a case of spontaneous acute tumor lysis in a patient of advanced gastric cancer with hepatic metastases and multiple lymphadenopathy. The biochemical finding of TLS improved with the management and tumor burden also showed slight response to the one cycled combination chemotherapy but the patient died of progressive pneumonia.
Tumor lysis syndrome (TLS) is an oncologic emergency that is caused by massive tumor cell lysis. It is commonly associated with hematological cancers like leukemia and lymphoma and uncommonly with solid nonhematologic tumors as well. However, spontaneous tumor lysis syndrome (STLS) without any cytotoxic chemotherapy rarely occurs in solid tumors. We describe a case of STLS in a metastatic adenocarcinoma of unknown primary and review the literature of STLS in solid non-hematologic tumors to identify various risk factors for pathogenesis of this entity.
The overall incidence of tumor lysis syndrome in adults is not well defined, and its occurrence can be unpredictable. Several strategies are available for the prevention and treatment of tumor lysis syndrome, with rasburicase being the most recent. Rasburicase is a recombinant urate oxidase enzyme approved for use by the Food and Drug Administration in patients who are at risk of developing tumor lysis syndrome or for the management of elevated uric acid levels. Clinical trials have demonstrated rasburicase to be effective in both the pediatric and adult populations, although the drug is currently indicated only for use in the pediatric population. Adverse effects associated with rasburicase can be significant, ranging from anaphylactic reactions to methemoglobinemia. To ensure accuracy of uric acid test results, special laboratory handling procedures must be followed while patients receive rasburicase. Compared with allopurinol and intravenous sodium bicarbonate, rasburicase is costly, and therefore judicious use of the medication is warranted.
Germ-cell tumors are a high-proliferative type of cancer that may evolve to significant bulky disease. Tumor lysis syndrome is rarely reported in this setting. The reports of three patients with germ-cell tumors who developed severe acute tumor lysis syndrome following the start of their anticancer therapy are presented. All patients developed renal dysfunction and multiorgan failure. Patients with extensive germ-cell tumors should be kept on close clinical and laboratory monitoring. Physicians should be aware of this uncommon but severe complication and consider early admission to the intensive care unit for the institution of measures to prevent acute renal failure.
Acute renal failure; germ-cell tumors; tumor lysis syndrome
Tumor lysis syndrome (TLS) presenting in absence of chemotherapy is a rare occurrence. One of the true oncological emergencies, it can lead to significant morbidity and mortality. TLS is a phenomena usually associated with tumor cell death after treatment. The etiology of the spontaneous TLS is not well understood, which complicates the diagnosis. TLS is well known to oncologists but physicians outside of this specialty have little or no experience with this condition. Early recognition and treatment are the keys to limiting the sequela of the condition. Spontaneous tumor lysis syndrome is rare but presents added risks to the patient because of the potential for delayed diagnosis and no benefit of pretreatment. Diagnosis may be further delayed because this may be the first symptom of underlying malignancy. Therefore, it is imperative that all clinicians are familiar with the syndrome to assure timely recognition.
Tumor lysis syndrome (TLS), a result of rapid cell lysis following tumor therapy, is a well recognized complication during the treatment of rapidly growing tumors. TLS rarely occurs in solid tumors. We present a case report of TLS in a patient with primary retroperitoneal soft tissue sarcoma. TLS occurred in the patient after four days’ combinational chemotherapy with cisplatin, adriamycin, and dacarbazine. These drugs were selected on the basis of an ex vivo ATP-based tumor sensitivity assay. TLS was properly controlled in the patient with concomitant remission of the sarcoma. Therefore, precautions should be taken to avoid this potentially fatal complication during treatment of solid tumors, especially with tumors highly sensitive to drugs.
tumor lysis syndrome; retroperitoneal soft tissue sarcoma; ATP-based tumor sensitivity assay (ATP-TCA)
Tumor lysis syndrome is a potentially life threatening condition which is most commonly encountered in patients being treated with chemotherapy. We report a case of spontaneous tumor lysis syndrome that developed intraoperatively in a patient with undiagnosed Burkitt's lymphoma. Characteristic electrolyte disturbances and white emulsion like urine following laparotomy and tumor handling intraoperatively suggested the diagnosis. This is a rare perioperative complication and the report emphasizes the importance of being vigilant in recognizing the same.
Continuous venous-venous hemodialysis; Burkitt lymphoma; intraoperatively; tumor lysis syndrome; ventricular arrhythmia
We designed a lentiviral vector expressing a chimeric antigen receptor with specificity for the B-cell antigen CD19, coupled with CD137 (a costimulatory receptor in T cells [4-1BB]) and CD3-zeta (a signal-transduction component of the T-cell antigen receptor) signaling domains. A low dose (approximately 1.5×105 cells per kilogram of body weight) of autologous chimeric antigen receptor–modified T cells reinfused into a patient with refractory chronic lymphocytic leukemia (CLL) expanded to a level that was more than 1000 times as high as the initial engraftment level in vivo, with delayed development of the tumor lysis syndrome and with complete remission. Apart from the tumor lysis syndrome, the only other grade 3/4 toxic effect related to chimeric antigen receptor T cells was lymphopenia. Engineered cells persisted at high levels for 6 months in the blood and bone marrow and continued to express the chimeric antigen receptor. A specific immune response was detected in the bone marrow, accompanied by loss of normal B cells and leukemia cells that express CD19. Remission was ongoing 10 months after treatment. Hypogammaglobulinemia was an expected chronic toxic effect.
Tumor lysis syndrome (TLS) is defined as a group of metabolic derangements that result from the massive and abrupt release of cellular components into the bloodstream after rapid lysis of tumor cells. Breakdown of released materials leads to a number of electrolyte abnormalities, including elevated uric acid concentrations in the blood (hyperuricemia), which carries potentially serious consequences. The diagnosis, prevention, and management of TLS is complicated by variability in definitions, differences in risk factors based on patient- and tumor-specific characteristics, and practitioner preferences in terms of pharmaceutical management strategies. The best prevention and management option for a particular patient depends on the patient’s baseline risk for TLS development, the severity of symptoms in the event of TLS development, practical management considerations, and financial implications of treatment.
tumor lysis syndrome; uric acid; rasburicase
Morbidity and mortality in patients with hematologic malignancies are significantly increased by development of acute renal failure. This is more likely in the developing world where facilities for renal replacement therapy are scarce. This review discusses the pathophysiology of acute renal failure due to tumor lysis syndrome in patients with Burkitt's lymphoma, the commonest hematological malignancy in the pediatric age group in sub-Saharan Africa, and evaluates the possible management options. Tumor lysis can also develop in association with other hematologic malignancies, both spontaneously and following treatment, and these principles are applicable in all such cases.
Acute renal failure; tumor lysis syndrome; Burkitt's lymphoma; hematologic malignancies; lymphoma; leukemia; management
We describe the case of a 5-year-old girl whose abdominal pain and distension were caused by Wilms tumor of the kidney. Because of the bilateral nature of her disease, she was spared biopsy or initial nephrectomy as part of her treatment course. Rather, she was treated presumptively for Wilms tumor based primarily on radiologic findings. Neoadjuvant chemotherapy consisting of vincristine, dactinomycin and doxorubicin was given to facilitate nephron-sparing surgery for tumor resection. Her initial chemotherapeutic course was complicated by tumor lysis syndrome manifested by elevated serum uric acid and was treated effectively with hyperhydration and alkalization of intravenous fluids. The patient's disease responded well to chemotherapy, and she underwent successful tumor excision after 12 weeks of chemotherapy. The resected tumor was identified as anaplastic Wilms tumor, illustrating that pathologic identification of Wilms tumor is possible even after multiple cycles of neoadjuvant chemotherapy and marked tumor shrinkage.
Multiple endocrine neoplasia type 1 (MEN-1) patients are prone to develop carcinoid tumors. Few cases report the development of gastrointestinal carcinoid tumors in patients with MEN-1 syndrome related tumors. This is the first paper to report the occurrence of an intestinal carcinoid tumour in association with a pituitary adenoma.
A sixty eight year old female presented with intestinal obstruction four years after transphenoidal pituitary resection for pituitary adenoma. During surgical exploration and lysis of adhesions, we accidentally discovered an intestinal carcinoid tumour. Resection of the involved small bowel segment and the draining lymph nodes was undertaken. Postoperative follow up showed no biochemical or radiological evidence of residual tumor.
Neuroendocrine tumors (NETs) may occur as part of familial endocrine cancer syndromes including MEN-1. It is recommended that clinicians search thoroughly for MEN-1 in patients presented with NETs, however, there is no current consensus for screening patients suspected to have MEN-1 to rule out NET.
We recommend screening patients suspected to have any familial type of endocrine tumors for the presence of NET.
AIM: To investigate the effectiveness of Clostridium novyi (C. novyi)-NT spores for the treatment of established subcutaneous pancreatic tumor in the syngeneic, immunocompetent Panc02/C57Bl/6 model.
METHODS: C. novyi-NT spores were applied intravenously to animals carrying established pancreatic tumors of three different sizes. Systemic immune responses in peripheral blood and spleen were examined by flow cytometry. Supplementary, cytotoxic activity of lymphocytes against syngeneic tumor targets was analyzed.
RESULTS: Application of spores identified, that (1) small tumors (< 150 mm3) were completely unaffected (n = 10); (2) very large tumors (> 450 mm3) responded with substantial necrosis followed by shrinkage and significant lethality most likely due to tumor lysis syndrome (n = 6); and (3) an optimal treatment window exists for tumors of approximately 250 mm3 (n = 21). In this latter group, all tumor-bearing animals had complete tumor regression and remained free of tumor recurrence. In subsequent tumor rechallenge experiments a significant delay in tumor growth compared to the initial tumor cell inoculation was observed (tumor volume at day 28: 197.8 ± 87.3 mm3 vs 500.1 ± 50.9 mm3, P < 0.05). These effects were accompanied by systemic activation of immune response mechanisms predominantly mediated by the innate arm of the immune system.
CONCLUSION: The observed complete tumor regression is encouraging and shows that immunotherapy with C. novyi-NT is an interesting strategy for the treatment of pancreatic carcinomas of defined sizes.
Bacteriolytic immunotherapy; Clostridium novyi-NT; Immune response; Pancreatic carcinoma
Tumor lysis syndrome (TLS) is a potentially lethal complication in cancer therapy. It may occur in highly sensitive tumors, especially in childhood cancer and leukemia, whereas, it is rare in the treatment of solid tumors in adults. TLS results from a sudden and rapid release of nuclear and cytoplasmic degradation products of malignant cells. The release of these can lead to severe alterations in the metabolic profile. Here, we present two cases of large hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) that resulted in TLS. Although TLS rarely happens in the treatment of adult hepatic tumor, only a few cases have been reported. We should keep in mind that all patients with HCC, particularly those with large and rapidly growing tumors, must be closely watched for evidence of TLS after TACE.
Hepatocellular carcinoma; Therapeutic chemoembolization; Tumor lysis syndrome
Tumor lysis syndrome (TLS) is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia in patients with a malignancy. When these laboratory abnormalities develop rapidly, clinical complications such as cardiac arrhythmias, acute renal failure, seizures, or death may occur. TLS is caused by rapid release of intracellular contents by dying tumor cells, a condition that is expected to be common in hematologic malignancies. However, TLS rarely occurs with solid tumors, and here we present the second chemotherapy-induced TLS in a patient with advanced gastric adenocarcinoma to be reported in the literature. We also provide information regarding the total cases of TLS in solid tumors reported from 1977 to present day. Our methodology involved identifying key articles from existing reviews of the literature and then using search terms from these citations in MEDLINE to find additional publications. We relied on a literature review published in 2003 by Baeksgaard et al., where they gathered all total 45 cases reported from 1977 to 2003. Then, we looked for new reported cases from 2004 to present day. All reports (case reports, brief reports, letters to editor, correspondence, reviews, journals, and short communications) identified through these searches were reviewed and included.
Tumor lysis syndrome (TLS) is widely recognized as a serious adverse event associated with the cytotoxic therapies primarily used in hematologic cancers, such as Burkitt lymphoma and acute lymphoblastic leukemia. In recent years, TLS has been more widely observed, due at least in part to the availability of more effective cancer treatments. Moreover, TLS is seen with greater frequency in solid tumors, and particularly in bulky tumors with extensive metastases and tumors with organ or bone marrow involvement. The consequences of TLS include the serious morbidity and high risk of mortality associated with the condition itself. Additionally, TLS may delay or force an alteration in the patient’s chemotherapy regimen. The changing patterns of TLS, as well as its frequency, in the clinical setting, result in unnecessarily high rates of illness and/or fatality. Prophylactic measures are widely available for patients at risk of TLS, and are considered highly effective. The present article discusses the various manifestations of TLS, its risk factors and management options to prevent TLS from occurring.
Acute renal failure; Allopurinol; Adverse events; Hematologic malignancies; Management; Prophylactic therapy; Solid tumors; Tumor lysis syndrome (TLS); Rasburicase; Uric acid
In female adolescents and young adults, malignancies of the genital tract are the most frequent type of cancer, closely followed by Hodgkin’s and non-Hodgkin’s lymphomas.
We report an unusual case of sporadic Burkitt’s lymphoma (BL) presenting with massive bilateral ovarian infiltration, peritoneal carcinomatosis and diffuse nodular lesions of the stomach and the intestine mimicking Krukenberg tumor. Diagnostic biopsies were obtained by endoscopy of the upper gastrointestinal tract. With intensive chemotherapy, complete remission was rapidly achieved, without life-threatening tumor lysis syndrome.
Besides metastatic gastric adenocarcinoma, BL is an important differential diagnosis in adolescents presenting with Krukenberg tumor.
Burkitt’s lymphoma; Gastric; Stomach; Adolescent; Epstein barr virus; Krukenberg tumor
We report a case of tumor lysis syndrome (TLS) in a patient with gallbladder carcinoma. TLS has not been reported in association with this type of tumor. TLS typically occurs in cases of highly proliferative hematological malignancies and small cell carcinoma. Two factors that may have contributed to TLS in this case include multifactorial mild acute renal failure shortly before the administration of chemotherapy and the aggressive morphology of the gallbladder carcinoma, which was a poorly differentiated sarcomatoid variant. This case raises concern for the development of TLS in certain types of patients with solid tumors.
tumor lysis syndrome; gallbladder carcinoma; solid tumors; gemcitabine; renal failure
The role of major histocompatibility gene products (i.e., HLA molecules) in rendering tumor cells resistant to natural killer (NK) cell-mediated lysis was investigated by using mouse monoclonal antibodies to bind and mask HLA or non-HLA gene products on the cell membrane of human allogeneic tumor targets. Enhanced lysis of resistant lymphoid and certain other solid tumor cell lines was observed only when monoclonals used reacted to class I and II HLA molecules but not non-HLA molecules on tumor targets. Enhanced lysis was not due to antibody dependent cellular cytotoxicity or due to an effect of antibody on NK effectors. Of importance, normal autologous and allogeneic human lymphocytes could not be lysed by NK cells despite blast transformation with mitogens or masking of HLA membrane determinants on blasts with monoclonal antibodies. Enhanced lysis, in the presence of antibody to HLA antigens, was not due to increased NK cell binding to tumor targets, but a consequence of enhanced postbinding lysis. Studies using granules obtained from NK cells indicated that masking of HLA antigens did not enhance the susceptibility of tumor targets to cytolysins. Such observations would suggest that HLA antigens on tumor targets inhibit the triggering of effector cells (and release of cytolysins) after recognition and binding of NK cells to target cells.
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.
Squamous cell carcinoma; Tumor lysis syndrome; Liver metastases; Maxillary sinus
Along with hydration and urinary alkalinization, allopurinol has been the standard agent for the management of hyperuricemia in patients with a high tumor burden at risk of tumor lysis syndrome; however, this agent often fails to prevent and treat this complication effectively. Rasburicase (recombinant urate oxidase) has been shown to be effective in reducing uric acid and preventing uric acid accumulation in patients with hematologic malignancies with hyperuricemia or at high risk of developing it. Rasburicase acts at the end of the purine catabolic pathway and, unlike allopurinol, does not induce accumulation of xanthine or hypoxanthine. Its rapid onset of action and the ability to lower pre-existing elevated uric acid levels are the advantages of rasburicase over allopurinol. Rasburicase represents an effective alternative to allopurinol to promptly reduce uric acid levels, improve patient’s electrolyte status, and reverse renal insufficiency. The drug, initially studied in pediatric patients with acute lymphoblastic leukemia and aggressive non-Hodgkin lymphoma, seems to show comparable benefit in adults with similar lymphoid malignancies or at high risk of tumor lysis syndrome. Current and future trials will evaluate alternative doses and different schedules of rasburicase to maintain its efficacy while reducing its cost. The review provides a comprehensive and detailed review of pathogenesis, laboratory, and clinical presentation of TLS together with clinical studies already performed both in pediatric and adult patients.
tumor lysis syndrome; urate oxidase; rasburicase; allopurinol; uric acid
Treatment of asymptomatic hyperuricemia to prevent gout, renal failure, or kidney stones is not justified. Similarly, the risks of developing either renal failure or kidney stones as a consequence of asymptomatic hyperuricemia are extremely low and do not justify intervention. Only in tumor lysis syndromes is therapy to prevent acute renal failure logical. Serum urate measurement should be requested in only very limited clinical circumstances.
A 55-year-old male patient with hepatitis B-related liver cirrhosis was found to have advanced hepatocellular carcinoma. His AFP was initially 9828 μg/L and rapidly dropped to 5597 μg/L in ten days after oral sorafenib treatment. However, he developed acute renal failure, hyperkalemia, and hyperuricemia 30 d after receiving the sorafenib treatment. Tumor lysis syndrome was suspected and intensive hemodialysis was performed. Despite intensive hemodialysis and other supportive therapy, he developed multiple organ failure (liver, renal, and respiratory failure) and metabolic acidosis. The patient expired 13 d after admission.
Sorafenib; Tumor lysis syndrome; Hepatocellular carcinoma; Hemodialysis; Hyperkalemia
Multiple regression models are used in a wide range of scientific disciplines and automated model selection procedures are frequently used to identify independent predictors. However, determination of relative importance of potential predictors and validating the fitted models for their stability, predictive accuracy and generalizability are often overlooked or not done thoroughly.
Using a case study aimed at predicting children with acute lymphoblastic leukemia (ALL) who are at low risk of Tumor Lysis Syndrome (TLS), we propose and compare two strategies, bootstrapping and random split of data, for ordering potential predictors according to their relative importance with respect to model stability and generalizability. We also propose an approach based on relative increase in percentage of explained variation and area under the Receiver Operating Characteristic (ROC) curve for developing models where variables from our ordered list enter the model according to their importance. An additional data set aimed at identifying predictors of prostate cancer penetration is also used for illustrative purposes.
Age is chosen to be the most important predictor of TLS. It is selected 100% of the time using the bootstrapping approach. Using the random split method, it is selected 99% of the time in the training data and is significant (at 5% level) 98% of the time in the validation data set. This indicates that age is a stable predictor of TLS with good generalizability. The second most important variable is white blood cell count (WBC). Our methods also identified an important predictor of TLS that was otherwise omitted if relying on any of the automated model selection procedures alone. A group at low risk of TLS consists of children younger than 10 years of age, without T-cell immunophenotype, whose baseline WBC is < 20 × 109/L and palpable spleen is < 2 cm. For the prostate cancer data set, the Gleason score and digital rectal exam are identified to be the most important indicators of whether tumor has penetrated the prostate capsule.
Our model selection procedures based on bootstrap re-sampling and repeated random split techniques can be used to assess the strength of evidence that a variable is truly an independent and reproducible predictor. Our methods, therefore, can be used for developing stable and reproducible models with good performances. Moreover, our methods can serve as a good tool for validating a predictive model. Previous biological and clinical studies support the findings based on our selection and validation strategies. However, extensive simulations may be required to assess the performance of our methods under different scenarios as well as check their sensitivity to a random fluctuation in the data.