RATIONALE: Radiolabeled monoclonal antibodies can locate cancer cells and deliver radiation to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of radiation and chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy plus etoposide followed by peripheral stem cell transplantation in treating patients who have advanced myelodysplastic syndrome or refractory leukemia.

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90 humanized monoclonal antibody M195 when combined with etoposide as a preparative regimen for autologous peripheral blood stem cell transplantation in patients with advanced myelodysplastic syndrome or refractory leukemia.
• Determine the qualitative toxicities associated with this regimen in this patient population.
• Assess preliminary information on engraftment following this conditioning regimen in these patients.

OUTLINE: This is a dose escalation study of yttrium Y 90 humanized monoclonal antibody M195 (Y90 MOAB M195).

Patients receive Y90 MOAB M195 IV over 40 minutes once between days -12 to -9 and etoposide IV over several hours on day -3. Peripheral blood stem cells or bone marrow are reinfused on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 until hematopoietic recovery.

Cohorts of 3-6 patients receive escalating doses of Y90 MOAB M195 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicities.

Patients are followed between days 10 and 14 and then monthly for 6 months.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 12 months.

• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

• Biological: filgrastim
• Drug: etoposide
• Procedure: autologous bone marrow transplantation
• Procedure: peripheral blood stem cell transplantation
• Radiation: yttrium Y 90 monoclonal antibody M195

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

  • Acute myeloid leukemia
  • Accelerated/blastic phase of a myeloproliferative disorder (i.e., greater than 10% blasts in bone marrow or presence of extramedullary disease)
  • Myelodysplastic syndrome

  • Acute lymphocytic leukemia with expression of CD33

    • Greater than 20% blast population
    • No evidence of CNS disease
• Relapsed after previously achieving complete remission
• Must have previously had peripheral blood stem cells or bone marrow cells harvested and cryopreserved while in remission
• Greater than 25% of bone marrow blasts must be CD33 positive

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• LVEF greater than 50% by ECG or MUGA
• No history of cardiomyopathy or symptomatic congestive heart failure

Pulmonary:

• DLCO at least 50% predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• HIV negative
• No other concurrent active malignancy
• No known sensitivity to E. coli derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified