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Medline ® Abstract for Reference 42

of 'Overview of neurologic complications of non-platinum cancer chemotherapy'

Disseminated necrotizing leukoencephalopathy: a complication of treated central nervous system leukemia and lymphoma.
Rubinstein LJ, Herman MM, Long TF, Wilbur JR
Cancer. 1975;35(2):291.
This report describes a form of disseminated necrotizing leukoencephalopathy that has been observed in four children with acute lymphoblastic leukemia, and one child with Burkitt's lymphoma terminating in a leukemic phase. In addition to systemic vincristine, cytosine arabinoside, cyclophosphamide, and steroids, these patients received courses of intrathecal methotrexate, cytosine arabinoside, and hydrocortisone, because of meningeal tumor cell infiltration. Whole brain radiation was also given either before or during intrathecal therapy. Three of the children had a progressive irreversible neurologic illness, which developed either at or shortly after the completion of combined triple intrathecal therapy, death ensuing approximately 2 months later. The neuropathologic lesions consisted of discrete multifocal necroses of coagulative type, apparently extending by confluence, and disseminated in the cerebral white matter in a random manner. In one case, extensive symmetrical demyelinating and necrotizing lesions involved the centrum ovale bilaterally. There was a remarkable absence of inflammatory cellular response and a relative paucity of macrophage reaction, with usually little or no tissue breakdown. In addition to demyelination and glial cell loss, there was striking axonal damage, with conspicuous axonal swelling both within and around the necrotizing lesions. The surrounding white matter showed focal status spongiosus and a moderate astrocytic response. Vascular fibrinoid necrosis was inconstant and, except in one case, rarely observed. The possible causal relationship of these lesions to combined triple intrathecal antimetabolite therapy and brain radiation is discussed.