Busulfan in Treating Children and Adolescents With Refractory CNS Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed CNS malignancy, including any of the following:

  • Primary malignant brain tumor refractory to standard therapy and metastatic to the cerebrospinal fluid (CSF) or leptomeningeal subarachnoid space

  • Recurrent or persistent leptomeningeal leukemia, lymphoma, or germ cell tumor refractory to conventional therapy

    • In second or greater relapse
    • CSF white blood count greater than 5 cells/mm3 with blasts on cytospin OR
    • Evidence of leptomeningeal tumor by MRI
• No concurrent bone marrow disease
• No obstruction or compartmentalization of CSF flow on CSF flow study

PATIENT CHARACTERISTICS:

Age:

• 3 to 21

Performance status:

• Lansky 50-100% (under 10 years)
• Karnofsky 50-100% (10 to 21 years)

Life expectancy:

• Greater than 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 75,000/mm^3

Hepatic:

• Bilirubin normal for age
• ALT and AST less than 5 times upper limit of normal (ULN)
• No hepatic disease

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Glomerular filtration rate greater than 70 mL/min
• No renal disease

Cardiovascular:

• No cardiac disease

Pulmonary:

• No pulmonary disease

Other:

• No uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
• At least 1 week since prior intrathecal chemotherapy (2 weeks for cytarabine) and recovered
• Evidence of subsequent disease progression

• Concurrent systemic chemotherapy allowed for recurrent disease after first course of treatment except for the following:

  • Chemotherapy targeted at leptomeningeal disease
  • Other phase I agent
  • Any agent that significantly penetrates the CSF (e.g., high dose methotrexate greater than 1 g/m2, thiotepa, high dose cytarabine, fluorouracil, IV mercaptopurine, nitrosoureas, or topotecan)
  • Any agent that causes serious unpredictable CNS side effects

Endocrine therapy:

• Prior dexamethasone allowed with decreasing or stable dose at least one week before study
• Concurrent dexamethasone or prednisone with chemotherapy regimen allowed

Radiotherapy:

• At least 1 week since prior focal irradiation to the brain or spine
• At least 8 weeks since prior craniospinal irradiation
• No concurrent cranial or craniospinal irradiation

Surgery:

• Not specified

Other:

• No other concurrent intrathecal or systemic therapy for leptomeningeal disease