Unrelated Bone Marrow Transplantation With Cyclophosphamide and Total Body Irradiation For Hematologic Malignancies and Bone Marrow Failure States
Unrelated Bone Marrow Transplantation With Cyclophosphamide and Total Body Irradiation For Hematologic Malignancies and Bone Marrow Failure States
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy and radiation therapy together with bone marrow transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving bone marrow transplant from an unrelated donor together with cyclophosphamide and total-body irradiation works in treating patients with hematologic cancer.
OBJECTIVES:
OUTLINE: All patients receive myeloablative therapy with high-dose cyclophosphamide and total body irradiation over 4 days; patients with severe aplastic anemia also receive antithymocyte globulin. Patients then undergo allogeneic bone marrow transplantation. Filgrastim (G-CSF) is given after transplant to accelerate engraftment. Sargramostim (GM-CSF) may be given in case of graft failure.
All patients receive graft-versus-host-disease (GVHD) prophylaxis with tacrolimus, methotrexate, and gamma globulin. Established GVHD is treated with corticosteroids and, as necessary, antithymocyte globulin.
Patients are followed at 100 days, 6 months, and 1 year after transplant, then annually thereafter.
PROJECTED ACCRUAL: A total of 10 patients per year will be accrued for this study over 5 years.
DISEASE CHARACTERISTICS:
One of the following hematologic malignancies/disorders:
Acute lymphoblastic leukemia
Acute myelogenous leukemia (AML)
In second or subsequent CR
In early first relapse
In full first relapse and failed conventional salvage therapy
In first CR with high-risk features, e.g., trisomy 8 or FAB 6/7
Chronic myelogenous leukemia in chronic, accelerated, or second chronic phase
Severe aplastic anemia that has failed at least 1 course of immunosuppressive therapy
Paroxysmal nocturnal hemoglobinuria with high-risk features (e.g., disseminated intravascular coagulation, thrombotic events)
Myelodysplastic syndrome, i.e.:
Secondary leukemia in CR following conventional-dose induction chemotherapy
Unrelated marrow donor available who is 8 out of 10-, 9 out of 10-, or 10 out of 10-antigen serologically HLA-matched at A, B, C, DRb, and DQB loci by molecular typing
No CNS malignancy
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Pulmonary:
Other:
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery