Reactions 1234 - 10 Jan 2009

He was tachypnoeic and required ventilation. MRI scansrevealed progressive leucoencephalopathy and T2 signal★ SAntineoplastics change. He was treated with plasmapheresis,immunoglobulins, corticosteroids, infliximab and rituximab.Leucoencephalopathy (first report for topotecan,He remained wakeful but unresponsive and developed labileclofarabine and muromonab CD3), transverseBP. Nine months posttransplant, he died suddenly frommyelopathy and peripheral neuropathy in paediatriccardiac arrest; his cancer was in remission at the time (nopatients: 4 case reportsautopsy was conducted).Four patients aged 12–15 years old developed

Author comment: "Etiology of this syndrome is unclear,leucoencephalopathy, transverse myelopathy and peripheralbut toxicity from chemotherapeutic agents is possible."neuropathy, following treatment with antineoplastics [dosages

not stated] for acute lymphoblastic leukaemia (patients 1, 2 Ledet DS, et al. Leucoencephalopathy, transverse myelopathy, and peripheralneuropathy in association with glutamic acid decarboxylase-65 (GAD) antibodiesand 4) and Ewing’s sarcoma (patient 3).in children with cancer. Journal of Child Neurology 23: 1357-1362, No. 11, NovPatient 1, a 13-year-old boy, received etoposide, cytarabine,2008 - USA 801118912vincristine, dexamethasone and intrathecal methotrexate for

disease relapse. After 2 months, he experienced left leg » Editorial comment: A search of AdisBase, Medline andweakness progressing to complete paraplegia over 2 weeks. Embase did not reveal any previous case reports ofHe lost vibration and proprioception up to his pelvis. The last leucoencephalopathy associated with topotecan, clofarabine ordoses of vincristine and methotrexate were 5 and 15 days muromonab CD3. The WHO Adverse Reactions database didbefore symptom onset, respectively. MRI scan findings over not contain any reports of encephalopathy (using WHO10 months were progressively consistent with terminology) associated with topotecan, but did contain fourleucoencephalopathy and myelopathy. Immunoglobulins reports associated with clofarabine, and 30 reports associated

with muromonab CD3. The database did not contain anywere administered and he gained neurological stability overreports of leukoencephalopathy (using MedDRA terminology)the next few weeks. Sensory function improved over theassociated with any of these three drugs.20 months after symptom onset, giving some return of

movement but no sphincter function.Patient 2, a 15-year-old boy, underwent a bone marrow

transplant after his diagnosis, with cyclophosphamide asconditioning. When he relapsed 7 months later, he receivedfurther chemotherapy. After CNS relapse 30 months later, hereceived intrathecal methotrexate, cytarabine, hydrocortisoneand topotecan with irradiation. He underwent furthertransplantation after 6 months, which involved fludarabine,thiotepa, melphalan and muromonab CD3. Twenty-eight daysafter transplantation, he developed progressive leg weakness,with impaired sensation up to the knees, abdominal musclespasms and urinary urgency. Over 19 months, MRI scansshowed progressive development of cerebralleucoencephalopathy and T3–T11 myelopathy.Plasmapheresis was unsuccessful, and further deteriorationnecessitated corticosteroids and immunoglobulins. After6 weeks, he had complete leg paralysis and dorsal columndysfunction up to the pelvis, with absent muscle reflexes. Atlast follow-up 2 years after symptom onset, he had somenormal function but had mild knee and ankle weakness anddorsal column dysfunction up to the knees.

Patient 3, a 12-year-old girl, was initially treated withifosfamide, cyclophosphamide, etoposide, doxorubicin andvincristine. A pulmonary tumour 6 months later was treatedwith cyclophosphamide, topotecan and vinblastine, and oraletoposide, gefitinib and irinotecan were administered forsubsequent tumour progressions. Three years after her initialdiagnosis, she underwent stem cell transplantation usingmelphalan, etoposide and carboplatin as conditioning. After100 days, her tumours progressed and further transplantationused melphalan, fludarabine and thiotepa. Six weeks after thesecond transplantation, she developed leg numbess and hermuscle reflexes were absent. Over 2 weeks, dorsal columndysfunction developed with sensory level at T9. She hadmarked hip girdle and mild distal weakness. MRI scans werenormal. She was administered immunoglobulins, and herneurological status was stable when she died from progressivetumours, 12 months after bone marrow transplantation.

On his third disease relapse, patient 4, a 14-year-old boy,received intrathecal methotrexate, hydrocortisone andcytarabine, followed by two courses of clofarabine. He thenunderwent a bone marrow transplant, with conditioning fromfludarabine, melphalan and thiotepa. Two weeksposttransplant, he reported leg weakness and reducedsensation, pinprick impairment up to T11 and dorsal columndysfunction at the toes [duration of therapy to reaction onsetnot clearly stated]. These symptoms progressed over 2 weeksto involve his upper limbs, and muscle stretch reflexesdisappeared. He became disoriented, and over the next2 weeks became unresponsive with absent ocular movements.

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