Tumor Lysis Mimicker: Rasburicase-Induced Methemoglobinemia and Hemolysis in an Undiagnosed G6PD-Deficient Patient with Relapsed DLBCL

Introduction/Background/Significance: Rasburicase is widely used to prevent tumor lysis syndrome (TLS) in high-risk hematologic malignancies. However, in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, it may cause life-threatening oxidative stress leading to hemolysis and methemoglobinemia. This case highlights a rare but critical complication that can mimic TLS progression and delay appropriate care.

Materials and Methods/Case Presentation/Objective: Case report

Results/Description/Main Outcome Measures: A 62-year-old African-American male with relapsed diffuse large B-cell lymphoma (DLBCL) was admitted for cycle 2 of R-ICE chemotherapy. Baseline evaluation revealed elevated uric acid (10.8 mg/dL), prompting single-dose rasburicase. Within 12 hours, he developed acute hypoxia, confusion, and hemoglobinuria. ABG revealed normal PaO₂ but low oxygen saturation, with methemoglobin level elevated to 17%. Labs demonstrated a sudden hemoglobin drop (11.8→7.2 g/dL), elevated LDH, undetectable haptoglobin, and Heinz bodies on peripheral smear—indicating oxidative hemolysis.

Rasburicase was immediately discontinued. The patient received supportive care with high-flow oxygen, red cell transfusions, and intravenous ascorbic acid. Methylene blue was avoided due to suspicion of G6PD deficiency, which was later confirmed. His condition improved, and he completed chemotherapy with allopurinol-based TLS prophylaxis. his case illustrates the importance of considering rasburicase-induced toxicity in patients with new-onset hypoxia and hemolysis. G6PD deficiency is more prevalent in individuals of African, Mediterranean, and Southeast Asian descent. Despite FDA recommendations, G6PD screening is often overlooked before rasburicase use. Misdiagnosis can lead to inappropriate treatment such as methylene blue, which exacerbates hemolysis.

Conclusions: Rasburicase can cause severe oxidative complications in G6PD-deficient patients. Routine screening and heightened clinical suspicion in high-risk populations are essential. Early recognition and multidisciplinary management can prevent fatal outcomes and guide safer TLS treatment strategies.

References

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