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

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:

• 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.

• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

• Biological: anti-thymocyte globulin
• Biological: filgrastim
• Biological: sargramostim
• Biological: therapeutic immune globulin
• Drug: cyclophosphamide
• Drug: methotrexate
• Drug: tacrolimus
• Procedure: allogeneic bone marrow transplantation
• Radiation: radiation therapy

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