Rasburicase-induced methemoglobinemia: The eyes do not see what the mind does not know

Rasburicase is indicated for the prevention and treatment of tumor lysis syndrome which can be a potentially life-threatening emergency. The drug has oxidizing potential and as an adverse effect, it can convert the ferrous form of iron in erythrocytes to its ferric form resulting in the formation of methemoglobin which makes the heme component incapable of carrying oxygen. Patients with glucose-6-phosphate dehydrogenase enzyme deficiency are at high risk of methemoglobinemia from oxidizing agents. Symptoms of methemoglobinemia range from none to life-threatening hypoxemia, cyanosis and respiratory compromise. Treatment is indicated at levels above 20% and at lower levels if the patient is significantly anemic. We present a case of a 60-year-old male with diffuse large B cell lymphoma at high risk of tumor lysis syndrome. Rasburicase was administered to prevent renal failure and further rise in uric acid. Twenty-four hours later, a bedside pulse oximetry showed an oxygen saturation ranging from 60 to 65% with minimal cyanosis. Co-oximetry revealed a methemoglobin level of 9.8%. Methylene blue was administered and the methemoglobin level decreased to 2.6%. However, the patient developed hemolysis several hours later, likely secondary to rasburicase and methylene blue, requiring transfusion support. We discuss this potentially fatal and initially asymptomatic adverse effect of rasburicase along with diagnostic and treatment considerations, and review the cases described in the current literature.

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Prevention and Treatment of Tumor Lysis Syndrome in the Era of Onco-Nephrology Progress

Kidney & Blood Pressure Research ◽

10.1159/000509934 ◽

2020 ◽

Vol 45 (5) ◽

pp. 645-660

Author(s):

Joanna Matuszkiewicz-Rowinska ◽

Jolanta Malyszko

Keyword(s):

High Risk ◽

Treatment Plan ◽

Diuretic Therapy ◽

Tumor Lysis Syndrome ◽

Phosphate Binders ◽

Tumor Lysis ◽

Threatening Condition ◽

Clinical Consequences ◽

Life Threatening ◽

Knowledge Of Cancer

Background: Tumor lysis syndrome (TLS) is an oncologic emergency due to a rapid break down of malignant cells usually induced by cytotoxic therapy, with hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and serious clinical consequences such as acute renal injury, cardiac arrhythmia, hypotension, and death. Rapidly expanding knowledge of cancer immune evasion mechanisms and host-tumor interactions has significantly changed our therapeutic strategies in hemato-oncology what resulted in the expanding spectrum of neoplasms with a risk of TLS. Summary: Since clinical TLS is a life-threatening condition, identifying patients with risk factors for TLS development and implementation of adequate preventive measures remains the most critical component of its medical management. In general, these consist of vigilant laboratory and clinical monitoring, vigorous IV hydration, urate-lowering therapy, avoidance of exogenous potassium, use of phosphate binders, and – in high-risk cases – considering cytoreduction before the start of the aggressive agent or a gradual escalation of its dose. Key Messages: In patients with a high risk of TLS, cytotoxic chemotherapy should be given in the facility with ready access to dialysis and a treatment plan discussed with the nephrology team. In the case of hyperkalemia, severe hyperphosphatemia or acidosis, and fluid overload unresponsive to diuretic therapy, the early renal replacement therapy (RRT) should be considered. One must remember that in TLS, the threshold for RRT initiation may be lower than in other clinical situations since the process of cell breakdown is ongoing, and rapid increases in serum electrolytes cannot be predicted.

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Impact of Early Rasburicase on Incidence and Outcomes of Clinical Tumor Lysis Syndrome in Lymphoma

Blood ◽

10.1182/blood-2018-99-115042 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1717-1717

Author(s):

Heather A Personett ◽

Erin F Barreto ◽

Kristen McCullough ◽

Ross Dierkhising ◽

Nelson Leung ◽

...

Keyword(s):

Uric Acid ◽

High Risk ◽

Hospital Admission ◽

Conflicts Of Interest ◽

Tumor Lysis Syndrome ◽

Kidney Injury ◽

B Cell Lymphoma ◽

Intermediate Risk ◽

Tumor Lysis ◽

New Onset

Abstract Introduction: Clinical tumor lysis syndrome (TLS), which manifests most often as acute kidney injury (AKI) is a common and devastating complication of rapidly proliferating hematologic malignancies. Epidemiologic studies of attributable risk factors for AKI in this setting are small, focus on only aggressive lymphomas rather than the more prevalent intermediate risk disease subtypes, and predate contemporary risk stratification, diagnostic criteria, and supportive care. Additionally, early administration of rasburicase to enhance uric acid (UA) elimination has been adopted without robust evidence in support of its impact on clinical outcomes, specifically, prevention of AKI. Methods: This was a retrospective cohort study of adult lymphoma patients at intermediate or high risk for TLS treated at Mayo Clinic between 2009 and 2017. Patients were excluded if they had AKI at hospital admission, received pre-admission rasburicase, or were on dialysis. Consensus definitions were used to stratify TLS risk and stage AKI. The incidence of new AKI in the setting of TLS was described along with predictors of its development, including early rasburicase use. Results: Of the 461 patients with a new lymphoma diagnosis during the study timeframe at intermediate or high risk of TLS, 78 were excluded, primarily due to prevalent AKI at hospital admission. The 383 included patients were predominantly at intermediate risk for TLS (73%) and had a diagnosis of Diffuse Large B-cell Lymphoma (64%). Incidence of new onset AKI during hospitalization was 6% and 91% of cases were stage 1. All new onset AKI occurred within the first 5 days of hospital admission. Independent predictors of new AKI included age > 60 years, history of chronic kidney disease or cardiovascular disease, and UA >8 mg/dL at any time during hospital admission. Rasburicase was given to 48 patients, 6 (13%) of whom still went on to develop AKI. Rapid UA reduction with rasburicase did not impact the risk of developing AKI (HR 2.3; p = 0.11). Uric acid level at the time of administration did not modify the effect of rasburicase on prevention of AKI (p = 0.36 for the interaction term). Conclusion: In conclusion, for lymphoma patients at intermediate or high risk for TLS, if not present at admission, AKI only infrequently developed during the course of a patient's hospitalization. Predictors of AKI included advanced age, comorbid conditions, and elevated UA levels. Early rasburicase administration, regardless of UA level, did not alter AKI risk. Disclosures No relevant conflicts of interest to declare.

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The Domino Effect-Treatment of Superior Vena Cava Obstruction Triggering Tumor Lysis Syndrome: A Case Report

SciMedicine Journal ◽

10.28991/scimedj-2021-0301-6 ◽

2021 ◽

Vol 3 (1) ◽

pp. 44-50

Author(s):

Suman Ghosh ◽

Tilak TVSVGK ◽

Venkatesan Somasundaram ◽

Mutreja Deepti

Keyword(s):

Superior Vena Cava ◽

Lymphoblastic Leukemia ◽

Superior Vena ◽

Tumor Lysis Syndrome ◽

Vena Cava ◽

Potassium Phosphate ◽

Successful Outcome ◽

Superior Vena Cava Obstruction ◽

Tumor Lysis ◽

Life Threatening

Oncological emergencies present in a multitude of manners-structural, metabolic, hematologic, etc. affecting multiple systems, often. Urgent institution of therapy is often required for a successful outcome. Occasionally, the treatment of one emergency can initiate a related or unrelated emergency, necessitating management of all the complications simultaneously. Superior vena cava obstruction (SVCO) is a medical emergency and most often manifests in patients with a malignant disease process requiring immediate diagnostic evaluation and therapy due to its’ life threatening presentation. The management of the SVCO is usually with chemotherapy, radiotherapy or intervention. In cases of large tumor burden, management of SVCO can trigger other complications. Tumor lysis syndrome is an oncologic emergency, which is characterized by a massive release of intracellular potassium, phosphate, and nucleic acid metabolites into the systemic circulation, which can be life-threatening. We present the case of a T-cell acute lymphoblastic leukemia with superior vena cava syndrome, developing tumor lysis syndrome on instituting definitive chemotherapy in a young patient. Doi: 10.28991/SciMedJ-2021-0301-6 Full Text: PDF

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Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An Evidence-Based Review

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.0177 ◽

2008 ◽

Vol 26 (16) ◽

pp. 2767-2778 ◽

Cited By ~ 406

Author(s):

Bertrand Coiffier ◽

Arnold Altman ◽

Ching-Hon Pui ◽

Anas Younes ◽

Mitchell S. Cairo

Keyword(s):

At Risk ◽

High Risk ◽

Tumor Lysis Syndrome ◽

The United States ◽

Standards Of Care ◽

Close Monitoring ◽

Tumor Lysis ◽

High Risk Patients ◽

Patients At Risk ◽

Risk Patients

PurposeTumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS.MethodsA panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used.ResultsNew guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involves similar recommendations, with the addition of aggressive hydration and diuresis, plus allopurinol or rasburicase for hyperuricemia. Alkalinization is not recommended. Although guidelines for rasburicase use in adults are provided, this agent is currently only approved for use in pediatric patients in the United States.ConclusionThe potential severity of complications resulting from TLS requires measures for prevention in high-risk patients and prompts treatment in the event that symptoms arise. Recognition of risk factors, monitoring of at-risk patients, and appropriate interventions are the key to preventing or managing TLS. These guidelines should assist in the prevention of TLS and improve the management of patients with established TLS.

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Hematologic and Oncologic Emergencies

Emergency Medicine ◽

10.1093/med/9780190852955.003.0008 ◽

2019 ◽

pp. 170-177

Author(s):

James McCue

Keyword(s):

Emergency Department ◽

Standardized Tests ◽

Tumor Lysis Syndrome ◽

Clinical Effects ◽

Tumor Lysis ◽

Oncologic Emergencies ◽

First Response ◽

Appropriate Treatment ◽

Wide Range ◽

Life Threatening

Hematologic and oncologic emergencies are an uncommon reason for people to present to the emergency department (ED), but when they do, it is important to know how to diagnose and treat these conditions because many of them are life threatening. Whether it is bleeding due to conditions such as hemophilia, von Willebrand’s disease, warfarin use, or dangerous conditions related to cancer such as tumor lysis syndrome or neutropenic fever, knowing the basics will help you manage these patients and also ace the standardized tests. This chapter presents questions related to the diagnosis, clinical effects, best first response in the ED, and most appropriate treatment of a wide range of these hematologic and oncologic emergencies.

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Spontaneous Tumor Lysis Syndrome

Case Reports in Oncology ◽

10.1159/000509643 ◽

2020 ◽

Vol 13 (3) ◽

pp. 1116-1124

Author(s):

Wiebke Wesemüller ◽

Christian Taverna

Keyword(s):

Tumor Therapy ◽

Tumor Lysis Syndrome ◽

B Cell Lymphoma ◽

Tumor Lysis ◽

Spontaneous Tumor ◽

Oncological Emergency ◽

Life Saving ◽

Cytotoxic Treatment ◽

Tumor Load ◽

Spontaneous Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) is a hemato-oncological emergency characterized by metabolic and electrolyte imbalances which are associated with disintegrating tumor cells. The syndrome is frequently observed when starting cytotoxic treatment of hematological malignancies, while the incidence of spontaneous tumor lysis prior to the start of tumor therapy is rare. Here, we present a case of spontaneous TLS in a male patient who was referred with unspecific symptoms and suspected metastatic malignancy. He developed acute renal failure before the diagnosis of a high-grade B-cell lymphoma (double hit lymphoma) and start of therapy. Although the course of TLS would have required intensive care, the patient rejected such treatment for personal reasons and died soon after the discontinuation of therapy. The case emphasizes the life-saving relevance of early detection and appropriate treatment of TLS. It also demonstrates the importance of actively screening for TLS, primarily in patients with malignant diseases and high tumor load, even if they are not receiving cytotoxic therapy.

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Tumor lysis syndrome: an uncommon complication of fludarabine therapy of chronic lymphocytic leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.7.2313 ◽

1998 ◽

Vol 16 (7) ◽

pp. 2313-2320 ◽

Cited By ~ 61

Author(s):

B D Cheson ◽

J N Frame ◽

D Vena ◽

N Quashu ◽

J M Sorensen

Keyword(s):

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Disease Duration ◽

Tumor Lysis Syndrome ◽

Laboratory Data ◽

Lymphocytic Leukemia ◽

Phase Ii Trials ◽

Tumor Lysis ◽

Laboratory Features

PURPOSE To quantify the incidence and severity of tumor lysis syndrome (TLS) as a consequence of fludarabine therapy in patients with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS A retrospective review and questionnaire follow-up of clinical and laboratory data were performed on patients with intermediate or high-risk CLL on the National Cancer Institute Group C protocol or special exception mechanisms, or phase II trials of fludarabine, for whom adverse drug reports of TLS were available. Fludarabine was administered at a dose of 20 to 40 mg/m2 per day for 5 days at monthly intervals. RESULTS Among the 6,137 patients, TLS was suspected in 26 (0.42%), with clinical and laboratory features consistent with TLS present in 20 (0.33%). Prophylaxis against TLS had been administered to 60% of these patients. Clinical or laboratory features were similar to patients who did not develop TLS. Of the patients with TLS, 90% had high-risk CLL, 60 months of prior disease duration, with a median pretreatment WBC of 109 x 10(9)/L, two prior regimens, lymphadenopathy in 89%, splenomegaly and/or hepatomegaly in 90%. TLS developed on approximately day 7 and lasted a median of 9.5 days. Dialysis was required in 30% during the TLS episode; 20% of patients died during cycle one of fludarabine therapy with renal failure, and another 20% died of infection or congestive heart failure. Six patients were retreated with fludarabine without recurrent TLS. CONCLUSION TLS after fludarabine therapy is extremely uncommon, but may be associated with significant morbidity and mortality.

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Fatal Spontaneous Tumor Lysis Syndrome in a Patient with Metastatic Colon Cancer: A Clinical Case of Rare Oncological Emergency

Case Reports in Gastroenterology ◽

10.1159/000507648 ◽

2020 ◽

Vol 14 (2) ◽

pp. 255-260

Author(s):

Inna Shaforostova ◽

Robert Fiedler ◽

Martina Zander ◽

Johannes Pflumm ◽

Wolfgang Josef März

Keyword(s):

Colon Cancer ◽

Case Reports ◽

Multiorgan Failure ◽

Tumor Lysis Syndrome ◽

Metastatic Colon Cancer ◽

Tumor Lysis ◽

Oncological Emergency ◽

Electrolyte Disturbances ◽

Life Threatening ◽

Spontaneous Tumor Lysis Syndrome

Tumor lysis syndrome (TLS) is a potentially life-threatening complication of chemotherapy. It usually occurs in rapidly proliferating hematological malignancies. TLS is deemed spontaneous (STLS) when it occurs prior to any cytotoxic or definite treatment. STLS is extremely rare in solid tumors. Here, we report a rare case of fatal STLS in a 47-year-old woman diagnosed with metastatic colon cancer. The patient developed acute renal failure with anuria, electrolyte disturbances, and metabolic acidosis before initiating chemotherapy. Despite appropriate management of TLS, including renal replacement therapy, she died within a few days from multiorgan failure. Only few other case reports of STLS associated with colon cancer have been reported in the literature.

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Spontaneous Tumor Lysis Syndrome in the Setting of B-Cell Lymphoma

Case Reports in Medicine ◽

10.1155/2010/610969 ◽

2010 ◽

Vol 2010 ◽

pp. 1-3 ◽

Cited By ~ 5

Author(s):

Mateusz Opyrchal ◽

Travis Figanbaum ◽

Amit Ghosh ◽

Vincent Rajkumar ◽

Sean Caples

Keyword(s):

Cell Lymphoma ◽

Early Recognition ◽

Tumor Lysis Syndrome ◽

Delayed Diagnosis ◽

B Cell Lymphoma ◽

Tumor Cell Death ◽

Tumor Lysis ◽

Spontaneous Tumor ◽

Underlying Malignancy ◽

Spontaneous 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.

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