RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of pyrazoloacridine given together with peripheral stem cell or bone marrow transplantation in treating young patients with high-risk neuroblastoma.

OBJECTIVES:

• Determine the maximum tolerated dose, in relation to infusion time, of high-dose pyrazoloacridine followed by autologous hematopoietic stem cell rescue in pediatric patients with high-risk neuroblastoma.
• Determine the dose-limiting toxicity of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Determine, preliminarily, the antitumor activity of this drug in these patients.

OUTLINE: This is a two-stage, dose-escalation study.

Patients without adequate cryopreserved hematopoietic stem cells undergo peripheral blood stem cell harvest or bone marrow harvest for autologous stem cells at least 2 weeks before study therapy.

Patients receive high-dose pyrazoloacridine (PZA) IV on day 0.

• Cohort 1: Groups of 3-6 patients receive escalating doses of PZA at a fixed infusion time until the maximum tolerated dose (MTD) is determined.
• Cohort 2: Groups of 3-6 patients receive PZA at the dose/hour established in cohort I at escalating infusion times until another MTD is determined.

In both cohorts the MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients receive filgrastim (G-CSF) IV or subcutaneously beginning on day 4 and continuing until blood counts recover. Patients also undergo reinfusion of stem cells over 15-30 minutes on day 4 as needed per protocol.

Patients are followed at days 28-35, every 3 months for 3 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 18-42 patients will be accrued for this study.

• Biological: filgrastim
• Drug: pyrazoloacridine
• Procedure: autologous bone marrow transplantation
• Procedure: peripheral blood stem cell transplantation

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed neuroblastoma

  • High-risk disease, as defined by the following:

    • Mixed response OR no response after completion of ≥ 4 courses of induction therapy OR
    • Progressive disease

    • Must meet at least 1 of the following criteria:

      • Histologically confirmed bone marrow disease by bilateral bone marrow aspirate and biopsy
      • Positive uptake at a minimum of one site by iodine I 123 or I 131 metaiodobenzylguanidine (MIBG) scan

      • Measurable disease

        • At least 20 mm by CT scan or MRI OR at least 10 mm by spiral CT scan

• No CNS parenchymal metastases by CT scan of the head with contrast or MRI of the head with gadolinium OR epidural metastases causing mass effect on the brain

  • Skull metastases allowed provided they are not associated with intracranial disease compressing or displacing the brain

PATIENT CHARACTERISTICS:

Age

• 1 to 30

Performance status

• Karnofsky 50-100% (over 16 years of age)
• Lansky 50-100% (1 to 15 years of age)

Life expectancy

• At least 2 months

Hematopoietic

• Absolute neutrophil count at least 750/mm^3
• Platelet count at least 75,000/mm^3 (transfusion independent)
• Hemoglobin at least 8 g/dL (transfusion allowed)

Hepatic

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 3 times ULN

Renal

• Glomerular filtration rate (GFR)* or creatinine clearance at least 100 mL/min
• Creatinine no greater than 1.5 times ULN NOTE: *Determined using blood draw method only

Cardiovascular

• Ejection fraction at least 55% by echocardiogram or MUGA OR
• Fractional shortening at least 27% by echocardiogram

Pulmonary

• No dyspnea at rest
• No oxygen requirement

Neurologic

• No history of seizures
• No history of cerebral bleeding or stroke
• No acute or chronic CNS disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

• No active infection requiring IV antivirals, antibiotics, or antifungals

  • Patients on prolonged antifungal therapy allowed provided they are culture-negative and biopsy-negative in suspected residual radiographic lesions

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Recovered from prior immunotherapy
• At least 7 days since prior myeloid growth factors
• At least 3 weeks since prior biologic agents
• At least 9 months since prior autologous hematopoietic stem cell transplantation (HSCT)
• No prior allogeneic HSCT

Chemotherapy

• See Disease Characteristics
• No prior pyrazoloacridine
• At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered

Endocrine therapy

• Not specified

Radiotherapy

• Recovered from prior radiotherapy
• At least 2 weeks since prior small-port radiotherapy to lesions not used for study eligibility
• At least 4 weeks since prior radiotherapy to study lesions
• At least 12 weeks since prior therapeutic doses of metaiodobenzylguanidine
• At least 6 months since prior craniospinal radiotherapy
• At least 6 months since prior radiotherapy to 50% or more of the pelvis
• At least 6 months since prior total body irradiation

Surgery

• Not specified

Other

• No concurrent antiretroviral therapy for HIV-positive patients