Complications of Intrathecal Chemotherapy in Adults: Single-Institution Experience in 109 Consecutive Patients

Abstract

Acute lymphoblastic leukemia and other aggressive lymphoid malignancies like Burkitt leukemia/lymphoma have high incidence of central nervous system (CNS) involvement. Various solid tumors, most notably breast cancer, can also metastasize into the CNS as a late stage complication causing devastating effects. Intrathecal (IT) chemotherapy consisting of methotrexate, cytarabine, or the two in combination is frequently used for the prophylaxis and treatment of CNS metastasis. Because of the high toxicity of these chemotherapeutic agents, however, their side effect profiles are potentially catastrophic. The incidence of neurotoxicity secondary to IT chemotherapy is well defined in the pediatric literature but is poorly reported in adults. Here, we investigated the incidence of neurologic and nonneurologic side effects secondary to IT chemotherapy in 109 consecutive adult patients over a two-year time period at hospitals associated with our institution. Of 355 IT chemotherapy treatments received by these patients, 11 (3.10%) resulted in paresthesias or paralysis, which we defined as significant neurologic events in our analysis. We also examined minor events that arose after IT chemotherapy, including back pain, headache, fever, vomiting, and asthenia. At least one of these occurred after 30.70% of IT chemotherapy doses. Clinicians involved in the care of patients receiving IT chemotherapy should be aware of these findings and consider treatment options lower rate of neurotoxicity such as high-dose systemic methotrexate.

Intrathecal 99m Tc‐DTPA imaging of molecular passage from lumbar cerebrospinal fluid to brain and periphery in humans

“…The final sample consisted of nine men and six women with a mean age of 38.7 ± 8.1 years (range: 23 to 49). The findings showed that the safety features built into our study design, the use of non‐cutting needles, were effective at reducing adverse events to rates far below those reported in clinical settings 22,23 . There were no medically meaningful adverse events related to the drug formulation.…”

Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood

“…Moreover, the preclinical results of intrathecal ASOs and adeno-associated viral (AAV) vector-mediated gene-delivery to CNS are promising in treatment other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), dementia disease and spinocerebellar ataxia (1,(39)(40)(41)(42). Another field is neuro-oncology, where intrathecal chemotherapy may be associated with dose-related neurotoxic side effects (43,44).…”

Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review

“…Furthermore, its use is not recommended in the presence of hydrocephalus (because, due to impaired CSF flow, it augments the risk of neurotoxicity, furthering intracranial pressure and consequently brain herniation and ischemia) [ 4 , 22 , 33 ] or nodular disease only (due to limited diffusion of ITT agents into the subependymal tissue) [ 1 , 7 , 24 , 34 ]. ITT also involves invasive procedures and has possible serious adverse effects [ 24 , 29 , 35 ], even if it seems not to negatively affect quality of life [ 25 , 32 ].…”