Fatal Tumour Lysis Syndrome Induced by Brigatinib in a Lung Adenocarcinoma Patient Treated With Sequential ALK Inhibitors: A Case Report

Tumour lysis syndrome (TLS) represents a group of fatal metabolic derangements resulting from the rapid breakdown of tumour cells. TLS typically occurs soon after the administration of chemotherapy in haematologic malignancies but is rarely observed in solid tumours. Here, we report a case of brigatinib-induced TLS after treatment with sequential anaplastic lymphoma kinase (ALK) inhibitors in a patient with advanced ALK-rearranged lung adenocarcinoma. The patient was treated sequentially with crizotinib, alectinib, and ensartinib. High-throughput molecular profiling after disease progression indicated that brigatinib may overcome ALK resistance mutations, so the patient was administered brigatinib as the fourth-line treatment. After 22 days of therapy, he developed oliguria, fever, and progressive dyspnoea. Clinical manifestations and laboratory findings met the diagnostic criteria for TLS. The significant decrease in the abundance of ALK mutations in plasma indicated a therapeutic response at the molecular level. Consequently, the diagnosis of brigatinib-induced TLS was established. To the best of our knowledge, this is the first case of TLS induced by sequential targeted therapy in non-small cell lung cancer. With the extensive application of sequential therapy with more potent next-generation targeted therapeutic drugs, special attention should be given to this rare but severe complication.

Predictors of laboratory spontaneous tumour lysis syndrome in children with high-grade tumours in Uganda

High-grade malignancy is endemic in sub-Saharan Africa and is prone to the spontaneous tumour lysis syndrome. However, data on spontaneous tumour lysis syndrome remain scanty in our setting. We sought to determine the prevalence and factors associated with laboratory spontaneous tumour lysis syndrome in children in Uganda. We conducted a cross-sectional study among children <18 years old with histologically confirmed high-grade malignancy between October 2013 and April 2014. Laboratory spontaneous tumour lysis syndrome was defined as the presence of ≥2 of each of hyperkalaemia, hypocalcaemia, hyperuricaemia and hyperphosphatemia prior to administration of chemotherapy when alternative diagnoses had been excluded. A p < 0.05 was considered statistically significant. Of 108 children, of median age 7.7 years, where boys outnumbered girls 2:1, high-grade, malignancy included Burkitt’s lymphoma, acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, acute myeloid leukaemia and Burkitt’s leukaemia, with 14 suffering with laboratory spontaneous tumour lysis syndrome. Hypocalcaemia was its most common electrolyte imbalance; and four children died prior to commencement of chemotherapy. Bulky disease, lactate dehydrogenase levels ≥500 iu/l and serum creatinine levels >1.2 mg/dl were associated with laboratory spontaneous tumour lysis syndrome. However, only bulky disease was significantly predictive of laboratory spontaneous tumour lysis syndrome. Such children would benefit from routine screening.

Follow-Up Study on Management of Tumour Lysis Syndrome with Single Low Fixed Dose (1.5 mg) of Rasburicase - A Tertiary Cancer Centre Experience from India

BACKGROUND Rasburicase (recombinant urate oxidase) has been proven to be an effective therapy for prevention of tumour lysis syndrome (TLS). The recommended daily dosing regimen of rasburicase is 0.2 mg/kg/day for 5 days which is expensive and unaffordable to many patients in the developing countries. The purpose of the present study was to evaluate the effect of single 1.5 mg dose rasburicase in the management of tumour lysis syndrome. METHODS This is a follow-up study done at our institute. Fifty (50) patients with tumour lysis syndrome who received rasburicase from August 2015 to January 2020 were enrolled in this study RESULTS Single dose of rasburicase is effective in decreasing serum uric acid level in significant number (N = 41) of patients. Percentage of patients having uric acid less than 7 mg after single dose of rasburicase in 48 hours - 82.9 % (N = 34) while 17 % (N = 7) were found to have uric acid levels of more than 7 mg/dl. The percentage of patients with uric acid levels more than 7 mg/dl reduced from 36.5 % after 24 hours to 17 % after 48 hours. This indicates that the uric acid levels show a declining trend even after 24 hours without giving an additional dose of rasburicase. There was no relationship between uric acid levels at 24 hours and percentage change in creatinine level from baseline to 24 hours (correlation coefficient (r) = -0.047, P = 0.770. Patients who required additional dose (N = 9) had high base line value of uric acid and their high value was maintained over the follow up period of three days. Patients with pre exiting kidney disease and high level of baseline uric acid also needed dialysis (N = 3). CONCLUSIONS In majority of patients, a single 1.5 mg dose of rasburicase is an effective way to reduce raised uric acid in appropriate circumstances. KEYWORDS Single Dose, Recombinant Urate Oxidase, Uric Acid, Leukemia, Tumour Lysis Syndrome, Rasburicase