Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission
Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Mycophenolate mofetil and donor white blood cells may prevent this from happening.
PURPOSE: Phase I/II trial to determine the effectiveness of combination chemotherapy and total-body irradiation followed by peripheral stem cell transplantation in treating patients who have acute lymphoblastic leukemia.
OBJECTIVES:
OUTLINE: This is a multicenter study.
Patients receive a nonmyeloablative conditioning regimen comprising fludarabine IV on days -4 to -2 and total body irradiation (TBI) on day 0. Children undergo allogeneic peripheral blood stem cell transplantation (PBSCT) or bone marrow transplantation after TBI on day 0. Adults undergo filgrastim (G-CSF)-mobilized allogeneic PBSCT after TBI on day 0.
Patients also receive graft-versus-host disease (GVHD) prophylaxis therapy comprising oral cyclosporine twice daily on days -3 to 56 and then tapered and oral mycophenolate mofetil once at 5-10 hours after transplantation on day 0 and then twice daily on days 1-27.
Patients who have no evidence of grade 2 or greater acute GVHD or clinically extensive chronic GVHD, have been off GVHD prophylaxis therapy for 1-2 weeks, and have stable or increasing minimal residual disease after discontinuation of GVHD prophylaxis therapy receive donor lymphocyte infusion (DLI) IV over 30 minutes. DLI repeats every 4 weeks for a total of 3 doses (if necessary).
Patients without a history of CNS leukemia and patients with a history of CNS leukemia previously treated with prophylactic craniospinal irradiation receive methotrexate (MTX) or cytarabine (ARA-C) intrathecally (IT) for a total of 2 doses before transplantation and for a total of 6 doses beginning on day 32 after transplantation. Patients with a history of CNS leukemia not previously treated with craniospinal irradiation undergo craniospinal irradiation for 11 days before conditioning regimen and then MTX or ARA-C IT for a total of 6 doses beginning on day 32 after transplantation. Male patients also undergo testicular radiotherapy for 7 days.
Patients are followed at 1, 2, 3, 6, 12, 18, and 24 months.
PROJECTED ACCRUAL: A total of 30 patients (20 adults and 10 children) will be accrued for this study within 2 years.
DISEASE CHARACTERISTICS:
Diagnosis of acute lymphoblastic leukemia (ALL)
Adult patients must meet 1 of the following criteria:
Age 50 to 75 with high-risk ALL in complete remission (CR) (less than 5% blasts by morphology on bone marrow aspirate and absence of peripheral blasts) or ALL in second CR (CR2) or greater
Age 18 to 50 with high-risk ALL in first CR (CR1) and either ineligible for conventional allogeneic transplantation (based on general medical condition) or refused conventional transplantation
High-risk adult ALL in CR1 includes patients meeting 1 or more of the following criteria:
Age 18 to 50 with ALL in CR2 or greater and ineligible for conventional allogeneic transplantation based on general medical condition
Age 18 to 50 with high-risk ALL in CR2 or greater and refused conventional allogeneic transplantation
Pediatric patients must meet 1 of the following criteria:
Under age 18 with high-risk ALL in CR1 and ineligible for conventional allogeneic transplantation based on general medical condition
High-risk pediatric ALL in CR1 includes patients meeting 1 or more of the following criteria:
Cytogenetic abnormalities
Failure to achieve CR after 4 weeks of induction chemotherapy
Persistent peripheral blasts after 1 week of induction chemotherapy
Under age 18 with CR2 or greater and ineligible for conventional allogeneic transplantation based on general medical condition
Age 12 and under allowed if approved by the principle investigator
No active CNS disease
Availability of a sibling donor (excluding an identical twin)
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Pulmonary:
Other:
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery