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Mitoxantrone is a synthetic antineoplastic anthracenedione used to treat hormone-refractory prostate cancer and acute leukemias. In addition, mitoxantrone is indicated for worsening relapsing and secondary progressive multiple sclerosis (MS). 1 The dose-limiting factor of mitoxantrone is cardiac toxicity, but therapy-related leukemia has been reported. 2 Reported cases of therapy-related leukemia following the use of mitoxantrone for MS have been myeloid forms. We report acute lymphoblastic leukemia following mitoxantrone therapy for MS.Case report. A 40-year-old African American woman with obesity and adult-onset diabetes presented with episodes of numbness, weakness, and ataxia over the past two decades. She also reported fatigue during warm weather and urinary urgency. She had normal mental status and cranial nerves, full strength in her arms and mild weakness in the legs, brisk reflexes in all extremities, and patchy areas of sensory loss in the legs. Her finger tapping was slow, and she had a broad-based gait. Brain MRI showed multiple periventricular T2/fluidattenuated inversion recovery hyperintensities consistent with demyelination, and CSF revealed two oligoclonal bands with elevated myelin basic protein and IgG synthesis index. Based on history, examination, imaging, and CSF analysis, the patient was diagnosed with relapsing-remitting MS and treated with interferon 1b.Her condition stabilized for 3 months, but she then began to experience frequent relapses and became wheelchair dependent. Repeat MRI demonstrated 11 new gadolinium-enhancing lesions; thus, mitoxantrone (12 mg/m 2 every 3 months) was added for worsening relapsing-remitting MS. Within 6 months of starting mitoxantrone, her condition improved, and she was able to ambulate with a walker. This represented a decrease in her Kurtzke Expanded Disability Status Scale (EDSS) score from 7.0 to 6.5.She continued on mitoxantrone and interferon 1b for 3 years, and her disease remained stable. However, 3 years after starting mitoxantrone, she had a myocardial infarction. An evaluation at that