Restrospective Review of Incidence, Complications and Management of Tumor Lysis Syndrome in High Risk Patients with Hematologic Malignancies

Background: The tumor lysis syndrome (TLS) has been reported to be common in hematologic malignancies, particularly those associated with a high proliferative index, high tumor burden, and highly effective therapy. The classification proposed by Cairo and Bishop (Cairo MS, Bishop M. Br J Haematol 2004; 127:3-11) provides criteria that define laboratory TLS (hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia) and clinical TLS (e.g., cardiac dysrhythmias, neuromuscular irritability, signs or symptoms clearly associated with hypocalcemia, seizures, sudden death, oliguria, elevations of creatinine above baseline). Patients with laboratory manifestations of TLS are considered to be at high risk for developing clinical TLS. It has been recommended that these patients receive rasburicase as part of initial management. The purpose of this restrospective study was to survey the incidence of laboratory/clinical TLS and to attempt to evaluate the role of allopurinol vs rasburicase for TLS prophylaxis and treatment at our institution.

Methods: We reviewed a series of consecutive patients presenting to our institution for initial inpatient therapy who were considered to be at high risk for tumor lysis by virtue of their hematologic diagnosis and need for aggressive chemotherapy. ICD9 codes were used to identify patients at 19 years of age or greater with Burkitt lymphoma, high tumor burden diffuse large B cell lymphoma (DLBCL)/mantle cell lymphoma (MCL), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)/lymphoma receiving their initial inpatient chemotherapy between 2007 and 2011. Electronic medical records were used to document demographic data, laboratory and clinical course information, including TLS prophylaxis/treatment strategies, from 3 days prior to 10 days post chemotherapy. Exclusion criteria were hypersensitivity to allopurinol or rasburicase or known glucose-6-phosphate dehydrogenase (G6PD) deficiency. Clinical and laboratory TLS was defined according to the method described by Cairo and Bishop.

Results: A total of 149 patients met the inclusion criteria. One hundred thirty seven (92%) patients had no presenting clinical or laboratory manifestations of TLS (“prophylaxis group”) and 12 (8%) patients with manifestations of TLS at presentation were considered as the “treatment group”. In the prophylaxis group, 128 (93%) patients received allopurinol alone, 3 (2%) received rasburicase alone and 6 (5%) received both allopurinol and rasburicase. In the treatment group, all 12 patients received both rasburicase and allopurinol. Four patients in the prophylaxis group that received allopurinol alone (4/128, 3%) eventually developed TLS which was managed successfully without the addition of rasburicase. The median total dose of rasburicase in the treatment group was 12 mg (range 6-18) and repeated doses were administered on only 3 occasions. In this group, arrhythmias due to TLS were observed in 1 (8%), acute kidney injury in 8 (67%) and hyperkalemia in 3 (25%) patients. Two patients (17%) required nephrology consult and 1 (8%) received hemodialysis. Three patients (25%) in this group died - 2 from acute respiratory distress syndrome and 1 from acute subdural hematoma with herniation and pneumonia. The highest incidence of TLS was in patients with AML, in whom 11 out of 81 (13.5%) patients developed TLS.

Conclusions: The incidence of TLS was approximately 11% in this high risk patient population. This study suggests that allopurinol as monotherapy can be effective as a prophylaxis strategy against TLS in a high risk patient population receiving initial chemotherapy. With appropriate monitoring, rasburicase may be added quickly in patients who develop progressive hyperuricemia during induction chemotherapy.