APHON Pediatric Chemotherapy-Biotherapy Renewal

Fludarabine. Fludarabine is an antimetabolite given to treat acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and as an agent in hematopoietic stem cell transplant (HSCT) preparative regimens. Neurotoxicity is rare when fludarabine is administered in standard doses. However, severe neurotoxicity syndrome has been described when the drug is administered at doses greater than 40 mg/m 2 /day. Blindness, encephalopathy, and coma are symptoms of the diffuse, necrotizing leukoencephalopathy that is the severe neurotoxicity syndrome associated with high doses of fludarabine (Sioka & Kyritsis, 2009). Nelarabine. Nelarabine, approved for use in treating T-cell ALL and T-cell lymphoma, is a prodrug of a purine antimetabolite, arabinofuranosylguanine (ara-G). It is metabolized in cells to the metabolite ara-G triphosphate (ara-GTP). Cell death results from the incorporation of ara-GTP into DNA. The cytotoxic effects of ara-GTP were found to have a 20 times greater effect on T cells than on B cells, and it was therefore approved by the U.S. Food and Drug Administration (FDA) for use in T-cell hematologic malignancies in 2005. It should be noted that nelarabine’s package insert contains a black-box warning for severe neurotoxicity, including mental status changes, severe somnolence, headache, paresthesia, dysesthesia, dizziness, seizures, and peripheral neuropathy, which can range from numbness and paresthesias to motor weakness and paralysis. These neurotoxicities were noted in both pediatric and adult patients. Nursing considerations include frequent monitoring during treatment and up to 24 hours after treatment, because neurotoxicity can be dose limiting. Adverse reactions related to demyelination and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome have been reported. It has also been noted that patients who have undergone intrathecal chemotherapy or are concurrently undergoing intrathecal chemotherapy or craniospinal radiation while receiving nelarabine may have increased severity of neurotoxic effects (Ngo et al., 2015). Neurotoxicity associated with nelarabine may be transient or may be long-lasting. Correlation between neurotoxicity and dose and/or concurrent intrathecal chemotherapy has also been found. Alkylating Agents Cyclophosphamide and ifosfamide . Cyclophosphamide and ifosfamide are both cell-cycle- nonspecific alkylating agents that are used for a variety of solid tumor malignancies. Cyclophosphamide is also used in treating hematologic malignancies and as an agent in preparative regimens for HSCT. Cyclophosphamide has been reported to have minimal neurotoxic effects. Blurred vision, dizziness, and confusion have all been reported but found to be reversible. Ifosfamide has been associated with an acute encephalopathy characterized by somnolence, hallucinations, agitation, and seizures that may lead to coma and even death. This encephalopathy, also referred to as ifosfamide neurotoxicity, can develop hours to days into a course of ifosfamide, and methylene blue can be used to treat the encephalopathy (Sioka & Kyritsis, 2009). Ifosfamide has also been linked to peripheral neuropathies in patients receiving the drug for bone and soft tissue sarcomas. This axonal peripheral neuropathy (arising from the axon of a nerve cell; Figure 2 ) can be quite painful and may discourage patients from ambulating on their own (Frisk et al., 2001).