Donor Bone Marrow Transplant in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders

Allogeneic Bone Marrow Transplantation Using Closely Matched Related and Unrelated Donors

RATIONALE: Giving chemotherapy and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related or unrelated donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow to make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well donor bone marrow transplant works in treating patients with leukemia, lymphoma, or nonmalignant hematologic disorders.

OBJECTIVES:

• Determine the survival of allogeneic bone marrow transplantation using closely matched related and unrelated donors in patients with malignant or nonmalignant hematological disorders.
• Determine the incidence and severity of acute and chronic graft versus host disease with this treatment regimen in these patients.
• Determine the relapse rates with this treatment regimen in those patients with malignant disorders.
• Determine the incidence and severity of infectious complications associated with this treatment regimen in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 1 hour on days -6 and -5, total body radiotherapy on days -3 through 0, and allogeneic bone marrow transplantation on day 0.

Patients with acute lymphocytic leukemia (ALL) receive intrathecal methotrexate at the beginning of the study. If CNS involvement is documented, patients receive a second dose of methotrexate 48 hours later followed by oral leucovorin calcium every 6 hours for 4 doses. Patients with ALL and/or CNS involvement receive intrathecal methotrexate every other week for 12 weeks after transplant.

Patients with prior CNS involvement receive radiotherapy for 2.5 weeks prior to transplant. Patients with ALL receive total body radiotherapy for 5 consecutive days prior to transplant.

Patients are followed once a week for 3 months, and then monthly for 1 year.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 6 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of one of the following:

  • Acute lymphocytic leukemia (ALL):

    • Complete remission (CR) 1 - high risk defined as overt CNS involvement or poor cytogenetics (additions, deletions, translocations, or multiple abnormalities)
    • CR2
    • Induction failures
    • Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt

  • Acute myelogenous leukemia (AML):

    • CR1 - high risk defined as poor cytogenetics (deletions, additions, multiple abnormalities)
    • CR2
    • Induction failures
    • Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt

  • Chronic myelogenous leukemia (CML):

    • Chronic phase (CP) 1
    • Accelerated phase/CP2 - patients in blast phase must undergo treatment and achieve a second chronic phase prior to transplant

  • Chronic lymphocytic leukemia (CLL):

    • Relapse - any stage; must have received no more than 3 prior regimens

  • Multiple myeloma:

    • At diagnosis - primary refractory
    • Relapse (no more than 2) - sensitive disease
    • Plasma cell leukemia
    • Inability to achieve a complete remission after autologous transplant (no older than 40)

  • Myelodysplasia - all subtypes

  • Myeloproliferative disorders - patients with poor response to medical therapy or cytogenetic abnormalities

  • Severe aplastic anemia (SAA):

    • Very SAA - at diagnosis
    • SAA - induction therapy

• Donors must be a phenotypic (6 out of 6) match or a one antigen (A or B) mismatch

PATIENT CHARACTERISTICS:

Age:

• 15 to 50

Performance status:

• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGOT and SGPT no greater than 3 times normal
• PT/PTT normal

Renal:

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

Cardiovascular:

• Left ventricular ejection fraction at least 45%
• No myocardial infarction within past 6 months
• No uncontrolled arrhythmias

Pulmonary:

• FEV1 at least 50%
• DLCO at least 50% predicted

Other:

• No active serious infection
• HIV negative
• Not pregnant or nursing
• No uncontrolled diabetes mellitus or thyroid disease

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified