Search Results (15)

Background/Objectives: Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency that occurs in pediatric patients undergoing chemotherapy. Severe complications, including acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and cardiogenic shock, may require extracorporeal membrane oxygenation (ECMO) support. Methods: This paper is a nonsystematic review of cases that synthesizes available case reports to evaluate the efficacy and outcomes of ECMO in pediatric TLS. Results: A systematic search identified five cases in which ECMO was used with a mean duration of 14 days. Survival rates were favorable and ECMO played a critical role in bridging these patients through multi-organ failure. Conclusions: While ECMO is a viable rescue therapy for severe TLS, associated complications, such as infections, bleeding, and neurological impairment, warrant careful patient selection and management. Future studies should explore standardized guidelines for the use of ECMO in pediatric oncology patients. Full article

Background: Renal adverse drug reactions (ADRs) associated with tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) are relatively rare, and there is currently no standardized protocol for their management. Therefore, this study aimed to summarize renal ADRs related to TKIs use in CML and propose an evidence-based approach to monitor and manage these ADRs. Methods: A systematic literature review was performed to identify renal ADRs associated with TKIs in CML. Two authors screened the search results and extracted data from 37 eligible studies. These findings were then used to develop a scheme for clinicians to monitor and manage these ADRs. Results: Overall, imatinib seemed to be significantly linked to renal adverse events compared to other TKIs, and switching to dasatinib or nilotinib significantly improved renal function. Similar events were reported with bosutinib, although they were not statistically significant. However, most of the renal events reported on dasatinib were described as nephrotic syndrome that resolved with switching to imatinib. Few cases were reported with nilotinib that described tumor lysis syndrome (TLS)-related kidney injury. Conclusions: Recommendations include monitoring for progressive decline in the estimated glomerular filtration rate with imatinib, nephrotic syndrome with dasatinib, and TLS with nilotinib. Additionally, holding the offending TKI and managing renal ADRs according to local guidelines were adopted more frequently than reducing the TKI dose. Full article

Background and Clinical Significance: Tumor lysis syndrome (TLS) is a rare occurrence in patients treated with venetoclax mono- or combination therapy, and clear protocols guiding TLS prophylaxis are lacking. Case Presentation: We present a 53-year-old male with a history of relapsed refractory multiple myeloma (RRMM) with t(11;14) treated with venetoclax, carfilzomib and dexamethasone (VenKd), resulting in TLS with subsequent renal failure. Repeat marrow biopsy showed no monoclonal plasma cells but extensive fibrosis. Venetoclax was reintroduced after two months with marrow recovery. Venetoclax was titrated from 200 to 400 mg daily alongside IV fluids and allopurinol without TLS recurrence. Conclusions: Here, we highlight the importance of risk stratification, dose titration, and TLS prophylaxis with venetoclax use in RRMM. Full article

Intermittent fasting (IF) has recently gained popularity due to its emerging benefits in reducing weight and improving metabolic health. Concurrently, novel agents (NAs) like venetoclax and Bruton tyrosine kinase inhibitors (BTKIs) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Unfortunately, it is unclear whether the associated risks of tumor lysis syndrome (TLS) and gastrointestinal bleeding (GIB) are increased in IF practitioners receiving NAs. This review explored the literature available on the permissibility of IF in CLL patients undergoing treatment with first-line NAs (FLNAs). Literature was scoped to identify IF patterns and the available data on TLS and GIB risks associated with food and fluid intake in CLL patients receiving FLNAs. Although current evidence is insufficient to recommend IF in this population, it may be possible for patients on venetoclax to conservatively practice fluid-liberal IF, provided that adequate hydration and the consistent administration of food are achieved. In contrast, considering the significant risk of TLS and the pharmacokinetics of venetoclax, patients should be discouraged from practicing fluid-restricted IF, especially during the ramp-up phase. Moreover, patients on BTKIs ought to refrain from IF due to the possible risk of GIB until further data are available. Further research is needed to provide conclusive recommendations. Full article

The treatment landscape for CLL has undergone a profound transformation with the advent of targeted agents (TAs) like Bruton’s Tyrosine Kinase inhibitors (BTKis) and BCL-2 inhibitors (BCL-2is). These agents target crucial cellular pathways in CLL, offering superior efficacy over traditional chemo-immunotherapy, which has led to improved progression-free and overall survival rates. This advancement promises enhanced disease control and potentially normal life expectancy for many patients. However, the journey is not without challenges, as these TAs are associated with a range of adverse events (AEs) that can impact treatment efficacy and patient quality of life. This review focuses on detailing the various AEs related to TA management in CLL, evaluating their frequency and clinical impact. The aim is to present a comprehensive guide to the effective management of these AEs, ensuring optimal tolerability and efficacy of TAs. By reviewing the existing literature and consolidating findings, we provide insights into AE management, which is crucial for maximizing patient outcomes in CLL therapy. Full article

Venetoclax, a highly selective, oral B-cell lymphoma 2 inhibitor, provides a robust targeted-therapy option for the treatment of chronic lymphocytic leukemia (CLL), including patients with high-risk del(17p)/mutated-TP53 and immunoglobulin heavy variable region unmutated CLL and those refractory to chemoimmunotherapy across all age groups. Due to the potent pro-apoptotic effect of venetoclax, treatment initiation carries a risk of tumor lysis syndrome (TLS). Prompt and appropriate management is needed to limit clinical TLS, which may entail serious adverse events and death. Venetoclax ramp-up involves gradual, stepwise increases in daily venetoclax dosing from 20 mg to 400 mg (target dose) over 5 weeks; adherence to on-label scheduling provides a tumor debulking phase, reducing the risk of TLS. The key components of safe venetoclax therapy involve assessment (radiographic evaluation and baseline blood chemistry), preparation (adequate hydration), and initiation (blood chemistry monitoring). In addition to summarizing the evidence for venetoclax’s efficacy and safety, this review uses hypothetical patient scenarios based on risk level for TLS (high, medium, low) to share the authors’ clinical experience with venetoclax initiation and present global approaches utilized in various treatment settings. These hypothetical scenarios highlight the importance of a multidisciplinary approach and shared decision-making, outlining best practices for venetoclax initiation and overall optimal treatment strategies in patients with CLL. Full article

Tumor lysis syndrome (TLS) is a potentially fatal oncological emergency that typically develops during the treatment of rapidly proliferating malignancies. It is infrequently reported in solid tumors, such as pulmonary adenocarcinoma. A 59-year-old male patient with shortness of breath presented with a 3.3 cm × 3.0 cm mass in the right upper lobe, along with massive right-sided pleural effusion. A percutaneous needle biopsy was performed, and a diagnosis of pulmonary adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation was made. The patient was treated with afatinib because of the malignant pleural effusion and multiple metastases to the intrathoracic lymph nodes, left scapula, and brain. After 4 days of afatinib treatment, he developed oliguric acute kidney injury and progressively worsening dyspnea. Based on the clinical and laboratory findings, the patient was diagnosed with afatinib-induced TLS. To the best of our knowledge, this is the first reported case of afatinib-induced TLS in pulmonary adenocarcinoma. Full article

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of malignancies, especially hematological tumors, but toxicities have tempered its success. The main impediments to the development of CAR-T cell therapies are the following: cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and on-target/off-tumor toxicity (OTOT). This review summarizes these side effects’ underlying mechanisms and manifestations over time. It provides potential prevention and treatment according to the consensus grading, stressing the significance of establishing strategies that anticipate, reduce, and navigate the beginning of these side effects. It is essential to fully comprehend the mechanisms underlying these toxicities to create efficient treatment and preventive approaches. Full article

Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment option in this setting. We report here the results of a multi-center retrospective study on 26 R/R AL amyloidosis patients treated off-label with venetoclax. The median lines of therapy prior to venetoclax was 3.5 (range 1–7), and 88% of our cohort had t (11;14). Twenty-two patients (85%) were previously treated with daratumumab. The overall hematologic response rate was 88%, 35% achieved a CR, and 35% achieved VGPR. The median event-free survival was 25 months (m) (95% CI 9.7 m-not reached), and the median overall survival was 33 m (95% CI 25.9–39.2 m). Most of the patients in this cohort are in ongoing deep responses and continuing venetoclax therapy. The treatment was relatively safe. One patient died due to infection, and there were two grade 3 infections in our cohort. Tumor lysis syndrome (TLS) was not seen in any patient. Dose reductions were frequent but did not affect the efficacy. These promising results require confirmation in a randomized controlled trial. Full article

CD20 monoclonal antibodies (mAbs) eliminate B cells in several clinical contexts. At least two of these Abs, obinutuzumab (OBI) and rituximab (RTX), induce quick elimination of targets and put cancer patients at risk of tumor lysis syndrome (TLS) within 12–24 h of the first dose. The mechanisms of killing can require the recruiting of effector mechanisms from the patient’s immune system, but they can induce direct killing as well. This can be more rapid than recruiting cellular effectors and/or complement. We showed here that OBI and RTX induce quick (<1 h) and high (up to 60% for OBI) killing of two different B cell lines. This was unveiled by using two different techniques that circumvent cell centrifugation steps: a Muse^® Cell Analyzer-based approach and a direct examination of the cells’ physical properties by using forward scatter (FS) area and side scatter (SS) area by flow cytometry. These results excluded the presence of aggregates and were also confirmed by developing a normalized survival ratio based on the co-incubation of RTX- and OBI-sensitive cells with MOLM-13, an insensitive cell line. Finally, this normalized survival ratio protocol confirmed the RTX- and OBI-direct killing on primary tumor B cells from B cell chronic lymphocytic leukemia (B-CLL) and Non-Hodgkin’s lymphoma (NHL) patients. Moreover, we unveiled that direct killing is higher than previously expected and absent in patients’ samples at relapse. We also observed that these mAbs, prior to increasing intracellular calcium levels, decrease calcium entry, although manipulating calcium levels did not affect their cytotoxicity. Altogether, our results show that direct killing is a major mechanism to induce cell death by RTX and OBI mAbs. Full article

Management of tumor lysis syndrome (TLS) associated with cancer chemotherapy for malignant tumors is important because of its potentially fatal course. The use of rasburicase, a recombinant urate oxidase, is recommended for TLS; however, because rasburicase is an enzymatic drug, one should be cautious of anaphylaxis during administration. Using claims data in Japan, we investigated the rate of rasburicase re-administration and the occurrence of anaphylaxis during re-administration in patients with hematopoietic malignancies in a multicenter setting. Re-administration of rasburicase was defined as administration after an interval of 21 days from the first dose. Of 373 patients, 18 were re-administered rasburicase (re-administration rate: 4.8%). No patient developed anaphylaxis. The median number of days from the first to the last dose of rasburicase was 256.5 days (interquartile range: 138.8–455.8 days). The median daily dose was 7.5 mg (4.5–11.3 mg), and the median total dose was 33.8 mg (19.1–64.1 mg). This claims database analysis revealed that the re-administration rate of rasburicase was low in Japanese patients with hematopoietic malignancies, suggesting that rasburicase was being used appropriately, and that associated anaphylaxis was not observed. Full article

Tumor lysis syndrome (TLS) is a common cause of acute kidney injury in patients with malignancies, and it is a frequent condition for which the nephrologist is consulted in the case of the hospitalized oncological patient. Recognizing the patients at risk of developing TLS is essential, and so is the prophylactic treatment. The initiation of treatment for TLS is a medical emergency that must be addressed in a multidisciplinary team (oncologist, nephrologist, critical care physician) in order to reduce the risk of death and that of chronic renal impairment. TLS can occur spontaneously in the case of high tumor burden or may be caused by the initiation of highly efficient anti-tumor therapies, such as chemotherapy, radiation therapy, dexamethasone, monoclonal antibodies, CAR-T therapy, or hematopoietic stem cell transplantation. It is caused by lysis of tumor cells and the release of cellular components in the circulation, resulting in electrolytes and metabolic disturbances that can lead to organ dysfunction and even death. The aim of this paper is to review the scientific data on the updated definition of TLS, epidemiology, pathogenesis, and recognition of patients at risk of developing TLS, as well as to point out the recent advances in TLS treatment. Full article

Over the last three decades, advancements in the diagnosis, treatment, and supportive care of patients with cancer have significantly improved their overall survival. However, these advancements have also led to a higher rate of cancer-related complications. Acute kidney injury (AKI) and chronic kidney disease (CKD) are highly prevalent in patients with cancer, and they are associated with an increased risk of all-cause mortality. This bidirectional interplay between cancer and kidney, termed “the kidney–cancer connection” has become a very active area of research. This review aims to provide an overview of some of the most common causes of AKI in patients with cancer. Cancer therapy-associated AKI is beyond the scope of this review and will be discussed separately. Full article

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. Full article

Up to 18% of patients with acute myeloid leukemia (AML) present with a white blood cell (WBC) count of greater than 100,000/µL, a condition that is frequently referred to as hyperleukocytosis. Hyperleukocytosis has been associated with an adverse prognosis and a higher incidence of life-threatening complications such as leukostasis, disseminated intravascular coagulation (DIC), and tumor lysis syndrome (TLS). The molecular processes underlying hyperleukocytosis have not been fully elucidated yet. However, the interactions between leukemic blasts and endothelial cells leading to leukostasis and DIC as well as the processes in the bone marrow microenvironment leading to the massive entry of leukemic blasts into the peripheral blood are becoming increasingly understood. Leukemic blasts interact with endothelial cells via cell adhesion molecules such as various members of the selectin family which are upregulated via inflammatory cytokines released by leukemic blasts. Besides their role in the development of leukostasis, cell adhesion molecules have also been implicated in leukemic stem cell survival and chemotherapy resistance and can be therapeutically targeted with specific inhibitors such as plerixafor or GMI-1271 (uproleselan). However, in the absence of approved targeted therapies supportive treatment with the uric acid lowering agents allopurinol and rasburicase as well as aggressive intravenous fluid hydration for the treatment and prophylaxis of TLS, transfusion of blood products for the management of DIC, and cytoreduction with intensive chemotherapy, leukapheresis, or hydroxyurea remain the mainstay of therapy for AML patients with hyperleukocytosis. Full article