Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Relapsed Acute Lymphocytic Leukemia

OBJECTIVES:

• Determine the efficacy of autologous peripheral blood stem cell (PBSC) transplantation for marrow reconstitution after high-dose carmustine, cytarabine, etoposide, and cyclophosphamide in children with relapsed acute lymphocytic leukemia.
• Determine the dose effect of autologous PBSC on engraftment in this patient population.

OUTLINE: Patients receive chemotherapy mobilization comprising cytarabine IV every 12 hours on days 1-5. When blood counts recover, autologous peripheral blood stem cells (PBSC) are harvested and selected for mononuclear cells, granulocyte-macrophage colony-forming units, and CD34+ cells.

Patients receive preparative regimen comprising carmustine IV on days -8 and -3, cytarabine IV every 12 hours and etoposide IV every 12 hours on days -7 to -4, and cyclophosphamide IV on days -2 and -1. PBSC are reinfused on day 0. Patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) beginning after PBSC transplantation. Male patients undergo radiotherapy to the testes before transplantation. Patients with a history of CNS leukemia undergo craniospinal irradiation before transplantation.

Patients are followed at 100 days, 6 months, and 1 year.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study within 5 years.

DISEASE CHARACTERISTICS:

• Diagnosis of acute lymphoblastic leukemia

• Pathologic evidence of relapse in marrow, CNS, or testes
• In second or later complete remission
• Ineligible for allogeneic transplantation:

• No suitable allogeneic donor (sibling or family donor or unrelated donor with no more than 1 HLA-A or -B antigen mismatch and HLA-DR identical) OR
• Ineligible for preparative regimen including total-body irradiation
• Peripheral blood stem cell collection feasible:

• Patient size generally at least 8 kg
• Able to place central venous catheter
• Patient cooperative

PATIENT CHARACTERISTICS:

Age:

• 1 to 19

Performance status:

• Not moribund

Life expectancy:

• No severe limits from disease other than leukemia

Hepatic:

• Bilirubin no greater than 3 times normal for age
• AST and/or GGT no greater than 3 times normal for age
• No evidence of hepatic synthetic dysfunction

Renal:

• GFR at least 50% of normal based on Glofil study or 12-hour creatinine clearance

Cardiovascular:

• Cardiac contractility normal on echocardiogram

Pulmonary:

• FVC and FEV_1 with or without DLCO at least 50% predicted

Other:

• No significant active infection
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified