Nelarabine-induced rhabdomyolysis in a patient with T-cell acute lymphoblastic leukemia: a case report

Nelarabine is an antineoplastic purine analog used for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL). The most prominent side effect of nelarabine are neurotoxicity and hematologic disorder, which are considered dose-limiting factors. Although clinical studies have reported myopathy due to nelarabine, actual detailed outcomes were not well-known initial approval. The incidence of nelarabine induced rhabdomyolysis has been reported at 2% in study in children. Cases of rhabdomyolysis have been reported in adults from medical facilities in the United Sates with renal dysfunction or severe muscle symptoms after administration of multiple courses of nelarabine. In this report, we discuss a case of rhabdomyolysis diagnosed after a single course of nelarabine. In this case, creatine kinase (CK) level was elevated in grade 4, without renal dysfunction and severe muscle symptoms.

A 46-year-old man from Japan was diagnosed with T-ALL and received a hematopoietic stem cell transplantation in first remission. However, the disease relapsed 6 months after transplantation. Nelarabine was selected as the next-line chemotherapeutic agent. The patient received 1500 mg/m² of nelarabine on day 1 followed by a dose on days 3 and 5. CK levels, which were baseline before treatment, increased to grade 4 (18,620 IU/L) on the 8th day of treatment. He was diagnosed as rhabdomyolysis due to nelarabine with little possibility of other factors. He complained only of mild pain in his upper extremities and no other symptoms were noticed. The patient was managed with hydration. The pain lasted approximately 7 days, but there were no sequelae secondary to the rhabdomyolysis. Because of the elevation of CK in grade 4, we avoided re-administration.

In the patient administrated nelarabine, CK level was elevated in grade 4, without other symptoms of rhabdomyolysis. The results suggest that CK may be elevated at the onset of rhabdomyolysis caused by nelarabine, even in the absence of other symptoms. Therefore, it was suggested that monitoring CK during nelarabine administration is important for detecting rhabdomyolysis before it becomes severe. We consider that CK should be monitored even in absence of symptoms.