title: Acute neurologic dysfunction associated with high-dose chemotherapy and autologous bone marrow rescue for primary malignant brain tumors.
abstract: Acute neurologic complications occurred 103 times in 50 (54%) of 92 patients (primarily children) treated with high-dose chemotherapy and autologous bone marrow rescue for primary central nervous tumors. Different types of neurologic compromise occurred during the chemotherapy infusion as compared to the first 100 days after the chemotherapy and the greater-than-100-day time period. The causes of the neurologic compromise were also time sensitive.
  
  
  BACKGROUND
  Results of treatment for children with primary brain tumors using high-dose chemotherapy with autologous marrow rescue (ABMR) have been encouraging. However, the neurotoxicity associated with this technique remains a major concern. We reviewed the records of 92 patients who underwent ABMR for malignant brain tumors between 1986 and 1992 for the occurrence and timing of acute neurologic dysfunction (AND).
  
  
  METHODS
  Individual investigators at the participating institutions retrospectively completed standardized forms on each patient. The manner in which the distribution of AND versus time of treatment emerged led to the establishment of distinct time periods for data analysis and discussion. The pre-ABMR period included those events that occurred during the chemotherapy infusion, the early posttreatment period included the first 100 days following bone marrow rescue, and the late posttreatment period was greater than 100 days following bone marrow rescue.
  
  
  RESULTS
  Fifty patients (54%) had 103 episodes of AND. AND included encephalopathies with or without hallucinations or coma (32), seizures (23), headaches (9), ataxia-tremor-dysarthria syndrome (7), anorexia and nausea syndrome (7) and others (25). During the chemotherapy infusion, encephalopathies and seizures were most common. Hallucinations occurred primarily related to drug infusion, while encephalopathies without hallucinations were usually due to demonstrable dysmetabolic states. In the 100 days following ABMR, dysmetabolic states and iatrogenic factors caused 45% and progressive disease caused 33% of AND. Greater than 100 days from ABMR, progressive disease caused 55% of AND; 7 patients were noted to develop chronic anorexia and nausea of unclear etiology. The occurrence of neurologic compromise was not related to the chemotherapy regimens, tumor histology, tumor location, patient age, prior treatment, or the amount of tumor at time of treatment. Dexamethasone use was the only clinical factor associated with AND (p < 0.004).
  
  
  CONCLUSIONS
  The cause of AND was definable for 95% of instances that occurred within 100 days of ABMR. Early AND was often iatrogenic and reversible. The greater the time from ABMR the more likely AND was due to progressive disease. Clinical factors could not predict the occurrence of AND as only the concurrent use of dexamethasone at the time of treatment proved significant. Although frequent, AND should not be considered a limiting toxicity of this approach or preclude the use of this technique.
authors.affiliation: Division of Neurology, Cooper Hospital, Robert Wood Johnson Medical School, Camden, NJ 08103, USA. kramered@umdnj.edu
authors.forename: E D
authors.initials: ED
authors.lastname: Kramer
authors.forename: R J
authors.initials: RJ
authors.lastname: Packer
authors.forename: J
authors.initials: J
authors.lastname: Ginsberg
authors.forename: S
authors.initials: S
authors.lastname: Goldman
authors.forename: S
authors.initials: S
authors.lastname: Thompson
authors.forename: L A
authors.initials: LA
authors.lastname: Bayer
authors.forename: V
authors.initials: V
authors.lastname: Shen
authors.forename: R
authors.initials: R
authors.lastname: Harris
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: J L
authors.initials: JL
authors.lastname: Finlay
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007049:Iatrogenic Disease; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009422:Nervous System Diseases / Q000209:etiology*; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents