Bone Marrow Transplant Plus Cyclophosphamide and Total-Body Irradiation in Treating Patients With Hematologic Cancer

OBJECTIVES:

• Study the curative potential of high-dose cyclophosphamide and total-body irradiation followed by rescue with bone marrow from volunteer HLA-matched donors in patients with a variety of hematologic malignancies and bone marrow failure states.
• Study the toxic effects associated with matched unrelated bone marrow transplantation in this patient population.
• Participate in collaborative research studies with the National Marrow Donor Program.

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

• In second or subsequent complete remission (CR)
• In first CR with high-risk features (e.g., Philadelphia chromosome-positive)
• In first relapse and failed conventional salvage therapy
• 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

• Standard-risk AML offered conventional-dose consolidation chemotherapy or autologous bone marrow transplantation
• Chronic myelogenous leukemia in chronic, accelerated, or second chronic phase

• No blast crisis
• 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.:

• Symptomatic, transfusion-dependent refractory anemia with excess blasts
• (RAEB) or RAEB in transformation
• 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:

• 17 to 60

Performance status:

• Karnofsky 70-100%

Life expectancy:

• No reduction due to other serious illness

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 3 mg/dL
• AST/ALT no greater than twice normal

Renal:

• Creatinine no greater than 2.0 mg/dL
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• Left ventricular ejection fraction at least 45%
• No severe hypertension

Pulmonary:

• DLCO, FEV_1, and FVC at least 50%

Other:

• HIV negative
• No active infection at time of transplant
• No advanced diabetes
• No significant neurologic deficit
• No active drug or substance abuse
• No emotional disorders
• Able to participate in frequent medical care for at least 1-2 years
• Willing to comply with National Marrow Donor Program policies

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified