MTX-related acute leukoencephalopathy
Six (18.75%) of the 32 patients developed MTX-related acute leukoencephalopathy. The details of the six patients are presented in Table 1. The manifestation of acute leukoencephalopathy was so mild that only one patient (No. 1) suffered from alalia. Two patients (No.3, 4) were asymptomatic, and three (No.2, 5, 6) had fatigue that was not paid attention to until the diagnosis of leukoencephalopathy. Five patients (No.2, 3, 4, 5, 6) were diagnosed with leukoencephalopathy during routine MRI after 6, 4, 4, 4, 6 cycles of chemotherapy, respectively.
For patient No.1, tumor cells were present in the CSF after one cycle of chemotherapy. MTX (12.5 mg) was injected intravenously once a week for the antitumor purpose. Three single doses were administered to this patient totally during the interval between two cycles of chemotherapy. As the patient developed alalia soon, she could not continue her next cycle of chemotherapy. Brain MRI and brain vessel MRI were performed thereafter. Brain MRI revealed multiple lesions in the bilateral cerebellar hemispheres, thalamus, basal ganglia region, lateral ventricle, radial coronal, center semicovale, bilateral frontoparietal temporal lobe and right occipital lobe. T1 weighted imaging (T1W1) revealed slightly low signal (Figs. 1A), T2 weighted imaging (T2WI) showed high signal (Figs. 1B), while flair image presented slightly high signal with blurred boundary (Figs. 1B). Diffusion weighted imaging (DWI) suggested limited diffusion of some lesions (Figs. 1D and 1E), and enhanced MTI suggested mild enhancement of some white matter lesions (Figs. 1F). There was no obvious abnormality on brain vessel MRI (Figs. 1G and 1h). Oligoclonal band (OCB) analysis found the presence of immunoglobulin G (IgGs) in her CSF. Leukoencephalopathy was diagnosed, and she was treated with intravenous methyl prednisolone at 2 mg/kg three times daily (which reduced over a 2-week period), oxygen support, and human blood albumin injection. Her condition was stable at the last follow-up.
In patient 2, screening MRI after the 6th cycle of chemotherapy revealed several infiltrative lesions that involved the bilateral frontal, parietal, temporal lobes, right cerebellar hemisphere and left pontile. T1WI showed slightly low signal (Figs. 2A and 2D), T2WI displayed high signal (Figs. 2B and 2E), while flair image revealed slightly high signal (Figs. 2C and 2F). The largest size of the lesion was about 1.5 cm, which was located in the right cerebellar hemisphere. Magnetic resonance spectroscopy (MRS) revealed Cho/NAA=1.78 of the lesion in the right cerebellar hemisphere, while Cho/NAA=0.97 of the lesion around the left lateral ventricle. This finding led to the differential diagnosis of tumefactive demyelinating lesions and MB recurrence. Cerebral blood flow (CBF) was measured, but no abnormal signal was observed during CBF subsequently. Leukoencephalopathy was diagnosed thereafter. Therefore, dexamethasone at 10 mg/d and oxygen support were given at a local hospital. A month later, the abnormal signal in white matter area was slightly improved compared with before (Figs. 3A, 3B and 3C). But the lesions in the cerebellar hemisphere increased to 2.5 cm with contrast enhancement (Figs. 3D, 3E and 3F). MRS revealed Cho+Cr/NAA=5.3 of this lesion. Besides, CBF revealed multiple cerebral hyperperfusion lesions as well. Relapsed disease was considered. The patient died two weeks later.
For patients No.3, 4, 5, 6, the findings were similar to those of patient 1. All of these cases were alive with severe neurological symptoms.
None of the patients in control group developed acute leukoencephalopathy. With the exception of acute leukoencephalopathy, there was no difference in the high-grade toxicity rate (grade ≥ 3) between the two groups.