Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

  • Acute leukemia

    • In second or subsequent complete remission (CR), as defined by absence of abnormal blast population by flow cytometry

    • In first CR with any of the following poor-risk cytogenetic features:

      • Alteration of chromosome 5 or 7
      • Multiple abnormalities
      • Philadelphia chromosome positive

  • Chronic phase chronic myelogenous leukemia (CML)

    • In first chronic phase and refractory to interferon alfa or imatinib mesylate
    • In second or subsequent chronic phase

  • Chronic lymphocytic leukemia, meeting 1 of the following criteria:

    • Received prior chemotherapy with a nucleoside analog and had remission lasting < 6 months

    • Received 1 prior therapy and has any of the following high-risk features:

      • Cytogenetic abnormalities of 17p, 11q
      • Mutations of the Zap70 gene
      • Somatically unmutated immunoglobulin heavy chain variable region genes

  • Hodgkin's lymphoma

    • Ineligible for autologous stem cell transplantation (SCT) due to any of the following exclusion factors:

      • LVEF < 45%
      • FEV_1 or FVC < 50% of predicted (75% of predicted in patients with prior thoracic or mantle radiotherapy)
      • Total bilirubin > 2.0 mg/dL (unless documented Gilbert's disease)
      • Creatinine > 2.0 mg/dL

  • Non-Hodgkin's lymphoma (NHL)

    • Low-grade NHL allowed provided patient had a remission duration of < 1 year after administration of any established, multi-agent chemotherapy regimen (e.g., CVP, CHOP, or rituximab in combination with CHOP)
    • Intermediate- or high-grade NHL allowed provided patient is ineligible for autologous SCT according to the criteria listed above
  • Multiple myeloma
  • Myelodysplastic syndromes
  • Paroxysmal nocturnal hemoglobinuria

  • Chronic myeloproliferative disorders other than CML, including any of the following:

    • Chronic myelomonocytic leukemia
    • Agnogenic myeloid metaplasia (or myeloid metaplasia with myelofibrosis), with hemoglobin < 10 g/dL OR WBC < 4,000/mm^3 or > 30,000/mm^3

    • Polycythemia vera or essential thrombocythemia in "spent" phase, with a history of 2 of the following:

      • Marrow fibrosis
      • Splenomegaly
      • Cytopenia (i.e., absolute neutrophil count < 1,500/mm^3, platelet count < 100,000/mm^3, hemoglobin < 10 g/dL)
    • Polycythemia vera or essential thrombocythemia with transformation to myelodysplastic syndromes or acute myeloid leukemia (requires treatment to achieve < 20% blasts in marrow)
• No smoldering myeloma
• Patients with acute myeloid leukemia or myelodysplastic syndromes must have had comprehensive cytogenetic evaluation of bone marrow specimen during active disease
• Ineligible for or refused bone marrow transplantation from an HLA-matched sibling or unrelated donor
• Ineligible for or refused autologous SCT

• Must have an HLA mismatched (i.e., 3/6, 4/6, or 5/6) related (first-degree relative)* donor available

  • Donor ≥ 18 years of age NOTE: *Patients with an inherited recombinant HLA haplotype may receive marrow from the parent in whose gamete the recombination occurred

NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

• 6 months to 74 years

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• See Disease Characteristics
• Bilirubin < 3.1 mg/dL

Renal

• See Disease Characteristics

Cardiovascular

• See Disease Characteristics
• LVEF ≥ 35%

Pulmonary

• See Disease Characteristics
• FEV_1 or FVC ≥ 40% of predicted in patients without prior thoracic or mantle radiotherapy (60% of predicted in patients with prior thoracic or mantle radiotherapy)

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• Geographically accessible
• No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment or follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior transfusions from donor

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified