• Complete radiographic response [ Designated as safety issue: No ]
  

• Duration of progression-free survival and overall survival [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Association of tumor BCL-6 expression with response [ Designated as safety issue: No ]
  
• Relationship among initial response to steroids, response to chemotherapy, and survival [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the complete radiographic response in patients with newly diagnosed primary CNS lymphoma treated with methotrexate and thiotepa.
• Determine the duration of progression-free survival and overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine whether tumor expression of BCL-6 is associated with response to this chemotherapy regimen and survival of these patients.
• Describe the relationship between initial response to steroids (if administered), response to this chemotherapy regimen, and survival of these patients.

OUTLINE: This is a multicenter study.

Patients receive thiotepa IV over 15 minutes on day 1. Patients also receive methotrexate IV over 4 hours on days 1 (8 hours after thiotepa) and 14. Beginning 24 hours after the start of methotrexate infusion, patients receive leucovorin calcium IV or orally every 6 hours until rescue is achieved. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving disappearance of enhancement of disease on MRI receive an additional 28-day course followed by maintenance therapy comprising thiotepa and methotrexate once a month for 11 courses.

Patients undergo neuro-ophthalmologic exams annually for 2 years.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 23-39 patients will be accrued for this study within 8-20 months.