Aggressive lymphoma, hemophagocytic lymphohistiocytosis, and G6PD crisis: a lytic cocktail

Abstract

Dear Editor, We report a case of aggressive lymphoma that received corticosteroids without tumoral lysis prevention and then salvage therapy with rasburicase, inducing glucose-6-phosphate dehydrogenase (G6PD) crisis. A 19-year-old male, originating from Madagascar, was admitted to the intensive care unit (ICU) for febrile hypotension. He had a 1-week history of fever and asthenia, treated with corticosteroids and josamycin by his general physician. Physical examination found febrile hypotension and hepatosplenomegaly, and blood tests revealed neutropenia, thrombocytopenia, hyperferritinemia, and hypertriglyceridemia, evocative of hemophagocytic syndrome. Tumor lysis syndrome (TLS) was suspected based on elevated uric acid, phosphate and potassium levels, and signs of acute kidney injury. The patient was treated with vasopressors, antibiotics, and rasburicase. He developed acute hemolysis and methemoglobinemia within 24 h. Rasburicase-induced G6PD crisis was diagnosed based on intra-erythrocyte G6PD measured at 1 UI/g/hemoglobin and MGG/cresyl blood smear (Fig. 1a, b). Investigations for the suspicion of hematological malignancy included a bone marrow aspiration that showed erythrophagocytosis (Fig. 1c) and atypical lymphocytes (Fig. 1d, e). Flow cytometry on bone marrow detected an abnormal population expressing cCD3+/CD5-/CD7-/ CD2-/CD4+/CD8-/CD30+ (Fig. 1f), consistent with ALK-negative anaplastic T-lymphoma, which was histologically confirmed. Treatment included etoposide, doxorubicin, cyclophosphamide, and steroids. The next day, he developed a digestive hemorrhage. Platelet count was normal, discordant with the previous assessment of thrombocytopenia. Platelet counts performed by Sysmex XN-impedance (Fig. 1g), Sysmex XN-optic (Fig. 1h), and Sysmex XN-fluorescent (Fig. 1i) were respectively 207 G/L, 206 G/L, and 52 G/L versus manual count of 20 G/L. Ten days after, he died of multiorgan failure. Rasburicase is indicated for TLS prevention before initiating corticosteroids or chemotherapy in patients with high-risk hematological neoplasms, such as non-Hodgkin’s lymphoma with high mass burden, suspected on LDH elevation or bulky mass [1]. Nevertheless, rasburicase is known to induce hemolysis crisis in patients with G6PD deficiency, a hereditary linked to X enzyme defect leading to glutathione stock reduction. G6PD deficiency [2]. In G6PD-deficient patients, rasburicase causes both hemolysis crisis and acute methemoglobinemia [3]. These complications may last for several days due to high dose administration and the relatively long half-life of rasburicase (18– 24 h) [3]. As hemolytic crisis may be lethal, G6PD testing is crucial before rasburicase administration in patients with a medical history suggestive of previous drug-induced hemolysis episode or originating from a high prevalence population, e.g., from Africa, especially sub-Saharan, Madagascar, Egypt, Middle-East, and Southeast Asia [2, 3]. This case also illustrates a rare false platelet count cause, when red blood cell (RBC) fragments are miscounted as platelets by three techniques. In samples containing abnormal cells, overestimation of platelet rates can be problematic as it may mask medically significant thrombocytopenia [4, 5]. Schizocytes or microcytes have Pierre-Edouard Debureaux and Mathilde Ruggiu contributed equally to this work.