Antineoplastics
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Reactions 1234 - 10 Jan 2009 He was tachypnoeic and required ventilation. MRI scans revealed progressive leucoencephalopathy and T2 signal ★ S Antineoplastics change. He was treated with plasmapheresis, immunoglobulins, corticosteroids, infliximab and rituximab. Leucoencephalopathy (first report for topotecan, He remained wakeful but unresponsive and developed labile clofarabine and muromonab CD3), transverse BP. Nine months posttransplant, he died suddenly from myelopathy and peripheral neuropathy in paediatric cardiac arrest; his cancer was in remission at the time (no patients: 4 case reports autopsy was conducted). Four patients aged 12–15 years old developed Author comment: "Etiology of this syndrome is unclear, leucoencephalopathy, transverse myelopathy and peripheral but 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 peripheral neuropathy in association with glutamic acid decarboxylase-65 (GAD) antibodies and 4) and Ewing’s sarcoma (patient 3). in children with cancer. Journal of Child Neurology 23: 1357-1362, No. 11, Nov Patient 1, a 13-year-old boy, received etoposide, cytarabine, 2008 - USA 801118912 vincristine, dexamethasone and intrathecal methotrexate for disease relapse. After 2 months, he experienced left leg » Editorial comment: A search of AdisBase, Medline and weakness progressing to complete paraplegia over 2 weeks. Embase did not reveal any previous case reports of He lost vibration and proprioception up to his pelvis. The last leucoencephalopathy associated with topotecan, clofarabine or doses of vincristine and methotrexate were 5 and 15 days muromonab CD3. The WHO Adverse Reactions database did before symptom onset, respectively. MRI scan findings over not contain any reports of encephalopathy (using WHO 10 months were progressively consistent with terminology) associated with topotecan, but did contain four leucoencephalopathy and myelopathy. Immunoglobulins reports associated with clofarabine, and 30 reports associated with muromonab CD3. The database did not contain any were administered and he gained neurological stability over reports of leukoencephalopathy (using MedDRA terminology) the next few weeks. Sensory function improved over the associated 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 as conditioning. When he relapsed 7 months later, he received further chemotherapy. After CNS relapse 30 months later, he received intrathecal methotrexate, cytarabine, hydrocortisone and topotecan with irradiation. He underwent further transplantation after 6 months, which involved fludarabine, thiotepa, melphalan and muromonab CD3. Twenty-eight days after transplantation, he developed progressive leg weakness, with impaired sensation up to the knees, abdominal muscle spasms and urinary urgency. Over 19 months, MRI scans showed progressive development of cerebral leucoencephalopathy and T3–T11 myelopathy. Plasmapheresis was unsuccessful, and further deterioration necessitated corticosteroids and immunoglobulins. After 6 weeks, he had complete leg paralysis and dorsal column dysfunction up to the pelvis, with absent muscle reflexes. At last follow-up 2 years after symptom onset, he had some normal function but had mild knee and ankle weakness and dorsal column dysfunction up to the knees. Patient 3, a 12-year-old girl, was initially treated with ifosfamide, cyclophosphamide, etoposide, doxorubicin and vincristine. A pulmonary tumour 6 months later was treated with cyclophosphamide, topotecan and vinblastine, and oral etoposide, gefitinib and irinotecan were administered for subsequent tumour progressions. Three years after her initial diagnosis, she underwent stem cell transplantation using melphalan, etoposide and carboplatin as conditioning. After 100 days, her tumours progressed and further transplantation used melphalan, fludarabine and thiotepa. Six weeks after the second transplantation, she developed leg numbess and her muscle reflexes were absent. Over 2 weeks, dorsal column dysfunction developed with sensory level at T9. She had marked hip girdle and mild distal weakness. MRI scans were normal. She was administered immunoglobulins, and her neurological status was stable when she died from progressive tumours, 12 months after bone marrow transplantation. On his third disease relapse, patient 4, a 14-year-old boy, received intrathecal methotrexate, hydrocortisone and cytarabine, followed by two courses of clofarabine. He then underwent a bone marrow transplant, with conditioning from fludarabine, melphalan and thiotepa. Two weeks posttransplant, he reported leg weakness and reduced sensation, pinprick impairment up to T11 and dorsal column dysfunction at the toes [duration of therapy to reaction onset not clearly stated]. These symptoms progressed over 2 weeks to involve his upper limbs, and muscle stretch reflexes disappeared. He became disoriented, and over the next 2 weeks became unresponsive with absent ocular movements. 1 Reactions 10 Jan 2009 No. 1234 0114-9954/10/1234-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
Transcript of Antineoplastics
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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Reactions 10 Jan 2009 No. 12340114-9954/10/1234-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
