Combination Chemotherapy Followed by Donor Bone Marrow Transplant or Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer or Genetic Disorders

Non-Ablative Chemotherapeutic Conditioning Before Allogeneic Stem Cell Transplantation

RATIONALE: Giving chemotherapy drugs, such as fludarabine and melphalan, before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of cancer or abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy followed by donor bone marrow transplant or peripheral stem cell transplant works in treating patients with hematologic cancer or genetic disorders.

OBJECTIVES:

• Determine the hematopoietic recovery in patients with hematologic malignancies or genetic disorders treated with fludarabine and melphalan followed by allogeneic or syngeneic bone marrow or peripheral blood stem cell transplantation.
• Determine the chemotherapeutic toxicity of this regimen in these patients.
• Determine the relapse and survival of patients treated with this regimen.
• Determine the incidence of graft-versus-host disease in patients treated with this regimen.

OUTLINE: Patients receive fludarabine IV on days -6 to -2 and melphalan IV on days -3 and -2. Patients with a non-HLA-identical family member may also receive anti-thymocyte globulin on days -4 to -1. Patients undergo allogeneic or syngeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients receive graft-vs-host disease prophylaxis comprising mycophenolate mofetil twice daily beginning on day -3, methylprednisolone beginning on day 5 and continuing over 8 weeks, and cyclosporine IV or orally beginning on day -3 and continuing until at least 6 months post-transplantation.

Patients are followed at 1, 3, and 6 months, and then at 1 year post-transplantation.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 5-6 years.

DISEASE CHARACTERISTICS:

• Clinically and/or histologically confirmed hematologic malignancy or genetic disorder

  • Chronic myelogenous leukemia

    • Typical blood and marrow morphology
    • Presence of Philadelphia chromosome OR
    • Molecular evidence of bcr/abl rearrangement if Philadelphia chromosome-negative

  • Acute myeloid leukemia, acute lymphocytic leukemia, myelodysplasia, or lymphoma

    • High risk of relapse or progressive disease
    • Typical clinical features and morphology in blood, marrow, lymph node, or other tissue by cytochemistry, immunophenotyping, and/or chromosomal abnormalities

  • Multiple myeloma

    • Typical marrow morphology, radiographic findings, and paraprotein

  • Aplastic anemia

    • Typical marrow and blood findings

  • Genetic disorder including storage disease (e.g., adrenoleukodystrophy), hemoglobinopathies (e.g., thalassemia), or severe immunodeficiency

• Unwilling to undergo conventional high-dose chemoradiotherapeutic conditioning prior to allogeneic stem cell transplantation OR

• Presence of other medical disorder which precludes high-dose chemoradiotherapeutic conditioning (e.g., cardiac disease or infection)

• Syngeneic twin, HLA-identical, or 1 or 2 HLA antigen-mismatched family member or unrelated donor

PATIENT CHARACTERISTICS:

Age:

• 1 to 80

Performance status:

• Karnofsky 50-100%

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• No other serious medical or psychiatric illness that would preclude study compliance
• Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• Not specified