The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia/lymphoma: challenges, opportunities, and future directions.

INTRODUCTION: Nelarabine is a guanine nucleoside analog and functions to terminate DNA synthesis in dividing cells. Pre-clinical and clinical studies have shown that it preferentially accumulates in T-cells where it exerts its cytotoxic effects. After generations of treatment protocol advances, it has been incorporated into numerous treatment regimens against T-lineage acute lymphoblastic leukemia/lymphoma (T-ALL/LLy). On 8 March 2023, the FDA approved the use of nelarabine for its use in T-ALL due to clear evidence of clinical benefits. This announcement concludes a nearly 6-decade period of evaluation for nelarabine and its role in the management of high-grade, aggressive T-cell malignancies. AREAS COVERED: We review the medicinal biology of nelarabine, its evaluation through decades of clinical studies, its dose-limited adverse effects, and its areas of highest impact in the treatment of T-ALL/LLy. EXPERT OPINION: We provide a context of when nelarabine might be considered in treatments against T-ALL/LLy, and also alternative strategies when it has or has not been used in therapies prior to relapse. We anticipate that an increasing number of treatment regimens will include nelarabine as a part of front-line therapy.

Intrathecal Methotrexate Containing the Preservative Benzyl Alcohol Erroneously Administered in Pediatric Leukemia Patients: Clinical Course and Preventive Process.

Administration of intrathecal chemotherapy for leukemia is a common procedure in pediatric oncology. The direct delivery of drug into the cerebral spinal fluid requires that no preservative be used. Preserved drugs administered in error can result in significant neurotoxicity. A case series is described where preservative-containing methotrexate was incidentally administered intrathecally. All patients were treated at Children's Hospitals and Clinics of Minnesota. Medical records of the patients affected were reviewed and abstracted for this report. Four children with acute lymphoblastic leukemia received 1 dose of intrathecal methotrexate that contained 0.07% benzyl alcohol in January 2019. Overall, minimal to no symptoms were seen after dosing. The error was traced to a drug shortage in which benzyl alcohol-containing methotrexate was obtained and incorrectly stocked. A novel replacement drug procurement process was developed within our institution. The process includes sequestered queues where a drug awaits evaluation and independent double check of entry accuracy in the electronic health record and pharmacy parenteral dose preparation software prior to release and use. In contrast to IV administration, intrathecal benzyl alcohol at concentrations ≥ 0.9% can cause significant neurotoxicity. Although minimal, if any, neurotoxicity was seen in patients who received a 10-fold lower concentration of benzyl alcohol than previously associated with complications, all institutions should recognize the potential for this error and implement similar safety precautions to ensure that this type of error will not occur.