Background and importance Methotrexate (MTX) is widely used in paediatric chemotherapy treatment and is effective. However, it presents with significant toxicity. Myelopathy is a rare but serious complication, usually related to mechanical damage caused by multiple lumbar punctures and the administration of drugs by this route. The main symptoms are loss of sensitivity, alteration of motor neurons, root pain and sphincter incontinence.
Aim and objectives We present a clinical case of a Caucasian girl with precursor B cell lymphoblastic lymphoma, stage IV, that affected the CNS type 3. She presented with neurotoxicity after administration of intrathecal MTX. She received treatment under the EURO-LB02 protocol.
Material and methods After seven doses of intrathecal triple (TIT) the patient began to experience distal tremor with numbness in the feet and slight ataxia. Gradually, the numbness increased and she developed areflexic paraparesis with static and kinetic ataxia that prevented her from walking. There was no cognitive impairment. MRI showed areas of leucoencephalopathy and homogeneous hyperintensity in the posterior segment from T1 to T12, suggesting dorsal myelitis. Folic acid and vitamin B12 levels were normal. Lymphoblastic invasion of the CNS was eradicated. To treat myelitis, she received methylprednisolone, dextromethorphan, s-adenosylmethionine, folinate, cyanocobalamin and intensive rehabilitation. Due to the patient‘s condition, we analysed 22 single nucleotide polymorphisms (SNPs) associated with the MTX metabolic pathway by TaqMan real time PCR.
Results 10 altered SNPs were found, mainly in genes encoding transport proteins (ABCB1 and ABCG2) and enzymes in the folate pathway (MTHFR) that could explain the toxicity manifested. However, there was low level evidence to support it. During subsequent cycles of chemotherapy, MTX was discontinued from TIT and intravenous MTX was gradually titrated to full doses. Currently, the patient is in the reinduction phase and has shown partial recovery from myelitis. She was rescued with leucovorin after intravenous MTX and levels of MTX were always within the normal range without notable toxicity.
Conclusion and relevance MTX may cause spinal cord dysfunction in children, especially when the intrathecal route is used. SNPs in enzymes involved in pharmacokinetics and pharmacodynamics may be the cause. However, more studies are needed to confirm these findings and translate them into information applicable to clinical practice.
Conflict of interest No conflict of interest
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.