Spontaneous tumor lysis syndrome in the setting of Candida albicans Fungemia.

Tumor Lysis Syndrome (TLS) is a metabolic emergency seen in patients who receive cytotoxic chemotherapy and can result in significant morbidity and mortality, especially in those patients with high tumor burden. Spontaneous tumor lysis syndrome (STLS) occurs in patients without preceding chemotherapy but may occur in the setting of glucocorticoid administration. We present a case of a 75-year-old male with a history of myelodysplastic syndrome who presented with shortness of breath and developed acute renal failure due to tumor lysis syndrome, likely triggered by candidemia. To our knowledge, this is the first known case of STLS in a patient with high tumor burden who did not receive corticosteroids but likely developed this condition in the setting of infection.

Bortezomib administration is a risk factor associated with the development of tumor lysis syndrome in male patients with multiple myeloma: a retrospective study.

BACKGROUND: Novel agents such as proteasome inhibitors have been developed for several years to treat multiple myeloma. Although multiple myeloma is a low-risk disease for developing tumor lysis syndrome (TLS), treatment with these novel therapies might increase TLS risk. Previous studies, mostly case reports or case series, have reported bortezomib-induced TLS in patients with multiple myeloma. This study aimed to investigate risk factors associated with TLS development in multiple myeloma patients. METHODS: We retrospectively investigated incidences of laboratory and clinical TLS (LTLS and CTLS, respectively) in patients who received primary therapy for treatment-naive, symptomatic multiple myeloma between May 2007 and January 2018. We used multivariate logistic regression analyses to evaluate the associations between TLS and several parameters previously reported to be associated with increased risk. RESULTS: This study included 210 patients with multiple myeloma, of which ten (4.8%) had LTLS and seven (3.3%) had CTLS. The characteristics of the administered anticancer or prophylactic antihyperuricemic agents were similar between patients with and without TLS. Multivariate analyses revealed that TLS was most strongly associated with bortezomib-containing therapy (odds ratio = 3.40, P = 0.069), followed by male sex (odds ratio = 2.29, P = 0.153). In a subgroup analysis focused on men, treatment with bortezomib-containing therapy was significantly associated with increased risk of TLS (odds ratio = 8.51, P = 0.046). CONCLUSION: In the present study, we investigated the risk factors associated with TLS development in 210 multiple myeloma patients, which, to the best of our knowledge, is the largest number of patients reported to date. Furthermore, this study is the first to evaluate TLS risk factors in MM by adjusting for the effects of potential confounding factors in patients' backgrounds. Consequently, we found that bortezomib-containing therapy increases the risk of TLS in male patients with multiple myeloma. TLS risk should be evaluated further in low-risk diseases such as multiple myeloma, since a significant number of novel therapies can achieve high antitumor responses.

Allantoin reduces cell death induced by cisplatin: possible implications for tumor lysis syndrome management.

Massive lysis of tumor mass in cancer patients under chemotherapy regimens generates high levels of uric acid, leading to what is known as tumor lysis syndrome (TLS). Rasburicase, a recombinant urate oxidase, converts urate to allantoin, which is readily excreted by the kidneys. Even though there is a high production of allantoin from urate in cancer patients following rasburicase treatment, there are no studies on how allantoin excess could interfere with chemotherapy. We have evaluated allantoin interference with cisplatin efficiency on the lung cancer cell line H460 in vitro. The cells were treated with cisplatin (33 µM), with or without allantoin, for 48 h, in the presence or absence of UV light, and N-acetyl-L-cysteine (NAC) for 24 h. Cell viability, cell cycle, ROS production, apoptosis and immunoblot assays were performed. We showed that allantoin reduced the apoptosis induced by cisplatin in the H460 cell line. However, the activity of carboplatin and oxaliplatin, betulinic acid, TIBA, UV and H2O2 was not affected by allantoin. NMR spectroscopy showed that allantoin reduces cisplatin activity through direct interaction with cisplatin.

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.

Venetoclax for the treatment of patients with chronic lymphocytic leukemia.

Venetoclax is a potent, selective inhibitor of BCL-2, a key regulator of the intrinsic pathway of apoptosis. In preclinical studies, venetoclax bound to BCL-2 with high affinity and rapidly induced apoptosis in chronic lymphocytic leukemia (CLL) cells. In early-phase clinical trials in CLL, venetoclax treatment led to tumor lysis syndrome in some patients with a large tumor burden, but this risk was subsequently mitigated by a revised study design that included lower initial dosing with intrapatient dose ramp up and close tumor lysis syndrome monitoring and prophylaxis. Other toxicities, such as neutropenia and gastrointestinal adverse events, were manageable. Venetoclax monotherapy resulted in durable and deep responses in patients with relapsed, refractory CLL, including for those with deletion 17p, leading to the approval of venetoclax by the US FDA for relapsed or refractory deletion 17p CLL, and recently to additional approvals in Europe and Canada. Trials also suggest that venetoclax induces deeper and more durable responses when used in combination with rituximab, and combination studies with other agents are ongoing. Phase III trials are also underway, and will provide data on the efficacy and safety of venetoclax in combination with monoclonal antibodies and targeted therapies in larger patient populations.

Severe Tumor Lysis Syndrome and Acute Pulmonary Edema Requiring Extracorporeal Membrane Oxygenation Following Initiation of Chemotherapy for Metastatic Alveolar Rhabdomyosarcoma.

We present an 8-year-old male with metastatic alveolar rhabdomyosarcoma (ARMS) who developed precipitous cardiopulmonary collapse with severe tumor lysis syndrome (TLS) 48 hr after initiation of chemotherapy. Despite no detectable pulmonary metastases, acute hypoxemic respiratory failure developed, requiring extracorporeal membrane oxygenation (ECMO). Although TLS has been reported in disseminated ARMS, this singular case of life-threatening respiratory deterioration developing after initiation of chemotherapy presented unique therapeutic dilemmas. We review the clinical aspects of this case, including possible mechanisms of respiratory failure, and discuss the role of ECMO utilization in pediatric oncology.

Reduced occurrence of tumor flare with flavopiridol followed by combined flavopiridol and lenalidomide in patients with relapsed chronic lymphocytic leukemia (CLL).

Flavopiridol and lenalidomide have activity in refractory CLL without immunosuppression or opportunistic infections seen with other therapies. We hypothesized that flavopiridol treatment could adequately de-bulk disease prior to lenalidomide therapy, decreasing the incidence of tumor flare with higher doses of lenalidomide. In this Phase I study, the maximum tolerated dose was not reached with treatment consisting of flavopiridol 30 mg m(-2) intravenous bolus (IVB) + 30 mg m(-2) continuous intravenous infusion (CIVI) cycle (C) 1 day (D) 1 and 30 mg m(-2) IVB + 50 mg m(-2) CIVI C1 D8,15 and C2-8 D3,10,17 with lenalidomide 15 mg orally daily C2-8 D1-21. There was no unexpected toxicity seen, including no increased tumor lysis, tumor flare (even at higher doses of lenalidomide) or opportunistic infection. Significant clinical activity was demonstrated, with a 51% response rate in this group of heavily pretreated patients. Biomarker testing confirmed association of mitochondrial priming of the BH3 only peptide Puma with response.

Tumor Lysis Syndrome: An Unreported Complication of Intrathecal Ara-C.

Intrathecal (IT) chemotherapy is an established method of preventing and treating CNS leukemia. Although this intervention is beneficial and necessary, understanding the potential adverse effects of IT chemotherapy is important so that these potential effects can be anticipated and prevented. Tumor lysis syndrome is a known complication of systemic chemotherapy and has also been reported as a rare complication after IT chemotherapy in patients with CNS disease. We report the first case of tumor lysis syndrome occurring in a patient with T-cell acute lymphoblastic leukemia without CNS disease. The systemic effects of the IT chemotherapy were confirmed by the decreased size of the presenting mediastinal mass.

[Bilateral leukemic optic nerve infiltration as the first manifestation of extramedullary relapse in T-cell acute lymphoblastic leukemia].

T-cell acute lymphoblastic leukemia is a hematologic malignancy with propensity to involve extramedullary organs including the eyes. Optic nerve infiltration is relatively rare. This is the case study of a 25-year-old- man who was in full remission following treatment for T-cell acute lymphoblastic leukemia and presented with bilateral leukemic optic nerve infiltration as the first manifestation of extramedullary relapse. The patient was treated with urgent radiotherapy and systemic dexamethasone. Over the following period, gradual resolution of optic disc swelling was noted in both eyes with marked improvement in vision in the right eye. Unfortunately, a few weeks later, a full blown hematological relapse was diagnosed. Salvage chemotherapy was instituted but was complicated by tumor lysis syndrome and septicemia that proved to be fatal. Ophthalmic assessment is essential in patients with hematological malignancies in order to diagnose ocular involvement as a result of malignant infiltration, hematological disturbances or as a complication of systemic therapy.

A case of tumor lysis syndrome following chemotherapy for a uterine epithelioid leiomyosarcoma with focal rhabdomyosarcomatous differentiation.

Tumor lysis syndrome (TLS) is a potential complication characterized by hyperuricemia, hyperphosphatemia, hyperkalemia and hypocalcemia due to massive necrosis of malignant cells after cytotoxic therapy. This fatal complication occurs frequently in tumors with hematological malignancies, such as acute lymphoblastic leukemia and Burkitt's lymphoma, and in other tumors with high proliferative rates and tumor burdens. TLS is rarely associated with the treatment of solid tumors. Herein, we report a case of TLS following the initial administration of effective chemotherapy for an epithelioid leiomyosarcoma with focal rhabdomyosarcomatous differentiation of the uterus.

Clinical characteristics of tumor lysis syndrome in childhood acute lymphoblastic leukemia.

Tumor lysis syndrome (TLS) is a common and fatal complication of childhood hematologic malignancies, especially acute lymphoblastic leukemia (ALL). The clinical features, therapeutic regimens, and outcomes of TLS have not been comprehensively analyzed in Chinese children with ALL. A total of 5537 children with ALL were recruited from the Chinese Children's Cancer Group, including 79 diagnosed with TLS. The clinical characteristics, treatment regimens, and survival of TLS patients were analyzed. Age distribution of children with TLS was remarkably different from those without TLS. White blood cells (WBC) count ≥ 50 × 109/L was associated with a higher risk of TLS [odds ratio (OR) = 2.6, 95% CI = 1.6-4.5]. The incidence of T-ALL in TLS children was significantly higher than that in non-TLS controls (OR = 4.7, 95% CI = 2.6-8.8). Hyperphosphatemia and hypocalcemia were more common in TLS children with hyperleukocytosis (OR = 2.6, 95% CI = 1.0-6.9 and OR = 5.4, 95% CI = 2.0-14.2, respectively). Significant differences in levels of potassium (P = 0.004), calcium (P < 0.001), phosphorus (P < 0.001) and uric acid (P < 0.001) were observed between groups of TLS patients with and without increased creatinine. Laboratory analysis showed that older age was associated with a higher level of creatinine. Calcium level was notably lower in males. WBC count, lactate dehydrogenase, and creatinine levels were significantly higher in T-ALL subgroup, whereas procalcitonin level was higher in B-ALL children. Older age, infant, a higher level of WBC and T-ALL were risk factors TLS occurrence. Hyperleukocytosis has an impact on the severity of TLS, while renal injury may be an important feature in the process of TLS.

Case series: acute tumor lysis syndrome in mutator mice with disseminated lymphoblastic lymphoma.

Acute tumor lysis syndrome (ATLS) is characterized by severe metabolic abnormalities and organ dysfunction resulting from rapid destruction of neoplastic cells. Metabolic disturbances are thought to be the primary cause of clinical ATLS symptoms, which include renal dysfunction, seizures, and cardiac arrhythmias. The histopathologic lesions associated with organ dysfunction are largely unknown because of the low rate of mortality of ATLS in humans and the few cases of ATLS identified in laboratory animals. Here, we describe histologic, immunohistochemical, and electron microscopic analyses of thirty-one ATLS cases from a cohort of 499 mice that are prone to spontaneous lymphoblastic lymphoma owing to genetic defects in DNA replication fidelity. Seventy-three percent of our cohort died with lymphoblastic lymphoma, and 8% of affected mice died with diffuse microthromboemboli consistent with ATLS. Mice with ATLS had a high spontaneous mortality rate (>50%), a large tumor burden with disseminated disease, and evidence of leukemia. Blood vessels in the lung, kidney, and other organs were occluded by microthromboemboli composed of chromatin, cellular debris, fibrin, platelets, and entrapped erythrocytes and malignant cells. This case series suggests that ATLS can occur at high frequency in mice with disseminated lymphoblastic lymphoma and leads to a high rate of spontaneous death from microthromboemboli.

Co-existence of Follicular Lymphoma in the Lymph Node with High-grade B Cell Lymphoma in the Bone Marrow of a Patient with Spontaneous Tumor Lysis Syndrome.

A significant percentage of B-cell lymphomas are characterized by bone marrow involvement (BMI) at diagnosis. In most cases, there is a concordance between the type of lymphoma present in the lymph node and the lymphoma present in the bone marrow. Herein, we presented a sixty-seven years old female patient, who was diagnosed with High-Grade B-cell Lymphoma (HGBL) in the bone marrow, while simultaneously, in the peripheral lymph node, the presence of Follicular Lymphoma (FL) was noted. The patient was presented to the hospital with spontaneous tumor lysis syndrome, a finding compatible with the aggressive course of the HGBL. To our knowledge, this is the first case of the co-existence of HGBL in the bone marrow and FL in a lymph node, which might be attributed to merely a coincidence or to the transformation of the cells in the preferable milieu of the bone marrow.

Diagnostic exercise: sudden death in a mouse with experimentally induced acute myeloid leukemia.

A 22-week-old female 129/SvEv mouse suddenly died in the context of an experiment aimed at defining the efficacy of valproic acid in a mouse model of PML/RARalpha-induced acute myeloid leukemia. Histologic analysis confirmed the mouse as being affected by a progressive myeloid leukemia, with infiltration of the spleen, bone marrow, liver, kidneys, and lungs. Variably sized intravascular clumps (emboli) of dense basophilic material admixed with necrotic or lytic neoplastic cells were also observed in multiple organs. A positive reaction to Feulgen and Hoechst stain confirmed the high content in chromatin of these basophilic emboli. Cleaved caspase-3 activity was demonstrated both in the leukemic infiltrates and among the intravascular necrotic or lytic neoplastic cells accompanying the basophilic emboli. A diagnosis of acute tumor lysis syndrome related to therapy-induced massive necrosis and/or apoptosis of leukemic cells with subsequent dissemination of emboli of chromatin was proposed.

[Tumor lysis syndrome]. / Síndrome de lisis tumoral.

Tumor lysis syndrome (SLT) is a rare and potentially fatal entity. It represents an oncological emergency. It can be diagnosed by its clinical presentation and also by laboratory results. In most cases it is presented as a complication of the chemotherapeutic treatment of oncohematological diseases with large tumor mass. Less frequently, a syndrome of spontaneous tumor lysis has been described, or secondary to the use of corticosteroids, hydroxyurea and radiotherapy. In its most severe forms it may require hospitalization in intensive care units and invasive therapeutic measures such as hemodialysis. We report four cases of SLT with unusual presentation characteristics admitted to our Medical Research Institute.

El síndrome de lisis tumoral (SLT) es una entidad poco frecuente y potencialmente fatal. Representa una emergencia oncológica. Puede diagnosticarse por su forma de presentación clínica y también por los resultados de laboratorio. En la mayoría de los casos se presenta como complicación del tratamiento quimioterapéutico de enfermedades oncohematológicas con gran masa tumoral. Con menor frecuencia se ha descrito un síndrome de lisis tumoral espontáneo, o secundario al uso de corticoides, hidroxiurea y radioterapia. En sus formas más graves puede requerir internación en unidades de terapia intensiva y medidas terapéuticas invasivas como la hemodiálisis. Comunicamos cuatro casos de SLT con características de presentación inusual internados en nuestro Instituto de Investigaciones Médicas.