Encephalomyelopathy following high-dose BCNU therapy

Burger, Peter C.; Kamenar, Elizabeth; Schold, S. Clifford; Fay, Joseph W.; Phillips, Gordon L.; Herzig, Geoffrey P.

doi:10.1002/1097-0142(19810915)48:6<1318::aid-cncr2820480612>3.0.co;2-r

Cited by 91 publications

(25 citation statements)

References 20 publications

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“…This case has been previously reported. 3 A lymph node biopsy confirmed a diagnosis of stage IVA Hodgkin lymphoma, mixed cellularity type. He was treated with vincristine, cisplatin, vinblastine, BCNU, procarbazine, bleomycin, and nitrogen mustard.…”

Section: Resultsmentioning

confidence: 90%

“…Neuropathologic findings in this case have been previously described. 3 Briefly, there were focal areas of myelin pallor and vacuolization in the temporal lobes and adjacent insula. Larger areas of amorphous necrotic material were seen in the subcortical white matter.…”

Section: Resultsmentioning

confidence: 99%

“…They served as the impetus for this report. The two additional cases, which had previously been reported, 2,3 were included because of similar clinical and pathologic findings. It will be demonstrated that chemotherapy-induced toxic leukoencephalopathy can be manifested in a wide and diverse range of signs and symptoms.…”

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confidence: 99%

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Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies

2004

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We have observed an increasing number of autopsies on patients with chemotherapy-related complications. One complication is toxic leukoencephalopathy, which is due to a direct toxic effect of chemotherapeutic agents on the central nervous system white matter. Autopsies of four cases of toxic leukoencephalopathy were performed following standard protocols. The brain and spinal cord were examined routinely, and histological sections were taken for evaluation. We report here three patients with hematologic malignancies and one patient with metastatic carcinoma with chemotherapy-induced leukoencephalopathy. The first was a 56-yearold male treated with multiple chemotherapeutics for multiple myeloma. He presented with confusion and focal seizures with a rapid progression to coma and decerebrate posturing. The second was a 36-year-old male who developed mental status changes, ataxia and dysarthria following treatment for lymphoma. The third was a 16-year-old male who developed a profound peripheral and central neuropathy after chemotherapy treatment for Tcell acute lymphoblastic leukemia. The fourth was a 49-year-old female patient who was treated with multiple chemotherapeutics for Stage II breast carcinoma and subsequently developed visual acuity and field defects. The neuropathologic findings in these cases, although similar, varied in severity and distribution. The white matter was affected by severe myelin pallor, edema, and a prominent macrophage infiltrate in each of the cases. The location and extent of the central nervous system pathology correlated with the type and severity of clinical symptoms. These four cases, with their varied presenting symptoms, clinical courses, and degree of pathology, emphasize the importance of considering toxic leukoencephalopathy as an etiology of acute neurologic deterioration following high-dose chemotherapy.

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

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Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies

2004

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“…Lung and liver toxicity contributed to 3 deaths in our series. We saw no evidence of encephalo- myelopathy but this has been described after high dose BCNU by others and should be included among the list of possible major complications (Burger et al, 1981;Wolff et al, 1987). The overall incidence of fatal non-haemopoietic toxicity in our series (3/22 patients) was lower than that reported by Wolff et al (1987).…”

Section: Pharmacokineticsmentioning

confidence: 99%

High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma

Mbidde

Selby²,

Perren³

et al. 1988

Br J Cancer

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Summary In a series of 22 patients, high dose BCNU (800-1,000 mgm-2) with autologous bone marrow transplantation was given as the first post-surgical treatment for grade IV astrocytoma and followed by full dose radiotherapy. When compared to historical experience and matched to control patients in national studies, there appeared to be a small prolongation of survival but no increase in the proportion of long survivors. Acute myelosuppression was mild but toxicity to lung and liver was substantial and limited further dose escalation. Late bone marrow failure was seen in 4 patients. Pharmacokinetic studies were performed and suggested that the late marrow failure was due to persistence of BCNU at the time of marrow return.Despite the suggestion of a prolongation of survival this approach is not routinely recommended and a randomised trial is probably not justified.The management of high grade glioma is unsatisfactory (Bloom, 1982). Radiotherapy following surgery will prolong survival by several months but long term survivors from grade IV astrocytoma (glioblastoma multiforme) are rare. Conventional chemotherapy has little to offer. These tumours share the relatively poor cellular chemosensitivity of most solid human cancers. In addition penetration of drugs into high grade gliomas is poor. They often have poor vascularisation and probably also a partially intact bloodbrain barrier in parts of the tumour (Workman, 1986).has been tested in conventional doses following surgery and radiotherapy for the treatment of high grade glioma. It gives a small, statistically significant, prolongation of survival but overall results are still poor with a median survival of only 12 months (Walker et al., 1980;Green et al., 1983). The dose of BCNU that can be given is limited by myelosuppression which is characteristically later in onset than that seen with most cytotoxic drugs (Phillips et al., 1986). The dose of BCNU can be increased when it is given with autologous bone marrow transplantation (ABMT) and such high doses of BCNU can produce useful palliative effects in patients whose grade gliomas recur after surgery and radiotherapy. Two recent studies have reported a small number of long term survivors with this approach (Fingert & Hochberg et al., 1984;Phillips et al., 1986). The late onset of myelosuppression (usually after 10 days) when coupled with the prompt recovery produced by autologous bone marrow transplantation (usually before 20 days) would be expected to result in a relatively short period of myelosuppression even for high dose BCNU. We have explored the use of high dose BCNU (HDBCNU), 800-1,000 mg m -2 with autologous bone marrow transplantation as the primary post-surgical treatment of grade IV astrocytoma followed by full dose radiotherapy. Our hypothesis was that the high dose of the drug when given to tumours before irradiation might be expected to result in improved penetration into the tumour and an enhanced anti-tumour effect which could then be supplemented by full dose radiotherapy. Tumour volume reducti...

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“…Of the other concurrent medications that are potentially central neurotoxic she also received lomustine, but according to data that we found, nitrosoureas are associated with little neurotoxicity at conventional doses, toxic effect is possible after cumulative and high iv doses, 7,8 which is not the case in our patient.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin-induced non-convulsive posterior reversible encephalopathy syndrome in a 41-year-old woman with metastatic malignant melanoma

Ocvirk¹,

Boc²,

Reberšek³

et al. 2009

Radiology and Oncology

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Encephalomyelopathy following high-dose BCNU therapy

Cited by 91 publications

References 20 publications

Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies

Chemotherapy-induced toxic leukoencephalopathy causes a wide range of symptoms: a series of four autopsies

High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma

Cisplatin-induced non-convulsive posterior reversible encephalopathy syndrome in a 41-year-old woman with metastatic malignant melanoma

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