Acute Tumor Lysis Syndrome during Oral Fludarabine Treatment for Chronic Lymphocytic Leukemia. Role of Treatment with Rasburicase

Abstract

Introduction: Oral fludarabine is the first oral formulation of a purine analogue available for clinical use which has produced encouraging results in patients with B-cell chronic lymphocytic leukemia (CLL). It has a similar tolerability profile to that of the intravenous formulation. Acute tumor lysis syndrome (TLS) induced by fludarabine appears to be a fairly unusual complication during the treatment of CLL. Case Report: The present report describes the case of a 78-year-old man who developed acute renal failure associated with TLS following the first course of oral fludarabine. Laboratory investigations fulfilled the TLS typical criteria, including hyperkalemia, marked hyperuricemia, hyperphosphatemia, hypocalcemia, and acute renal failure. Despite the many documented side effects of oral fludarabine, there is only one similar case of oral fludarabine-induced TLS reported to date. Conventional therapy with short-term supportive hemodialysis and a short treatment of rasburicase for 2 days achieved a complete recovery of renal function and a decrease of the urate level to within the normal range. Conclusions: Clinicians should be alert to this potentially life-threatening metabolic emergency among CLL patients treated with oral fludarabine.

Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus

“…Chronic myeloid leukaemia (CML) was an LRD (Fig 1) in the present risk classification system. To take into account the therapy‐dependent risk for TLS in patients with CLL (Cheson et al , 1998; Dillman & Hendrix, 2003; Hussain et al , 2003; Hummel et al , 2005; Calvo‐Villas et al , 2008; Lin, 2008; Phelps et al , 2009), CLL was an LRD when treated exclusively with alkylating agents, but an IRD in the presence of an elevated WBC (≥50 × 10 9 /l) and/or were treated with targeted and/or biological therapies (fludarabine/rituximab).…”

Tumor Lysis Syndrome as a Consequence of Chronic Lymphocytic Leukemia Treatment With Fludarabine and Rituximab

“…While only 6 cases of TLS associated with fl udarabine therapy have been reported since 1989 (up to 2011) [5,6], cautious monitoring of patients treated with fl udarabine should be undertaken, even after completion of the chemotherapy course. The same applies to the patients who are about to be treated with rituxan (especially after the fi rst dose), since there have been two cases reported of Rituxaninduced TLS in CLL patients in the literature.…”

Development of fludarabine formulations in the treatment of chronic lymphocytic leukemia

“…TLS can be easily prevented with allopurinol prophylaxis and the encouragement of hydration with oral fluids during treatment 59. Two case reports describing TLS after oral fludarabine were published 60,61. One of these patients developed TLS during the two first treatment cycles.…”