Non-Ablative Allo HSCT For Hematologic Malignancies or SAA

DISEASE CHARACTERISTICS:

• Histologically proven high-risk hematologic malignancy

  • Acute non-lymphocytic leukemia (ANLL) after induction failure, or in first complete remission (CR) with high-risk features, including any of the following:

    • Stem cell or biphenotypic classification (AML-M0)
    • Erythroleukemia (AML-M6)
    • Acute megakaryocytic leukemia (AML-M7)
    • Cytogenetic markers indicative of poor prognosis
    • Failure to achieve CR after standard induction therapy
  • Acute lymphocytic leukemia (ALL) or ANLL in relapse or second or subsequent remission

  • Chronic myelogenous leukemia (CML) in chronic or accelerated phase

    • Patients with CML in blast crisis are eligible after reinduction chemotherapy places them in chronic phase

  • High-risk ALL in first CR with high risk defined by presence of t(4;11), t(9;22) translocation, hyperleukocytosis (initial WBC greater than 30,000/mm^3), or failure to achieve CR by day 28 after standard induction

    • No T-cell ALL or t(8;14) positive B-cell ALL in first remission with hyperleukocytosis

  • Myelodysplastic syndrome by peripheral blood smear and bone marrow examination

    • Refractory to medical management OR
    • Cytogenetic abnormalities predictive of transformation into acute leukemia including 5q-, 7q-, monosomy 7, and trisomy 8 OR
    • Evidence of evolution to AML (e.g., refractory anemia with excess blasts (RAEB) or RAEB in transformation)

  • Multiple myeloma, non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after autologous stem cell transplantation (SCT)

    • At least 3 months since prior autologous SCT

  • Hodgkin's lymphoma, NHL, or multiple myeloma beyond first CR or primary induction failures whose disease has demonstrated sensitivity to pre-transplantation cytoreduction (defined as greater than 50% reduction in tumor burden)

    • Mantle zone NHL allowed after induction therapy
  • Myeloproliferative disorder that is non-responsive to medical management and requires allografting, unless evidence of grade 3 or worse myelofibrosis on marrow biopsy OR

• Histologically proven acquired severe aplastic anemia (SAA) that is recurrent or unresponsive after anti-thymocyte globulin and/or cyclosporine

  • SAA defined by at least 2 of the following conditions:

    • Granulocyte count less than 500/mm^3
    • Platelet count less than 20,000/mm^3
    • Absolute reticulocyte count less than 20,000/mm^3 after correction for hematocrit

• Ineligible for full ablative conditioning due to any of the following conditions:

  • Prior extensive therapy (more than 2 salvage chemotherapy regimens and/or autologous transplantation)
  • Over age 55 OR
  • Under age 55 with comorbid disease (e.g., suboptimal cardiac, pulmonary, or renal function and/or prior life-threatening infection)
• HLA-A, B, and DR phenotypically identical sibling donor OR
• HLA-A, B, and DR identical genetically matched unrelated donor
• No ANLL in first CR (less than 5% blasts in marrow) with translocations t(8;21) and inv(16) unless failed first-line induction therapy OR
• No ANLL in first CR (less than 5% blasts in marrow) with translocations t(15;17) abnormality unless failed first-line induction therapy OR molecular evidence of persistent disease
• No active CNS disease

PATIENT CHARACTERISTICS:

Age:

• 0 to 70

Performance status:

• Zubrod 0-1
• Karnofsky 80-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• See Disease Characteristics

Hepatic:

• ALT/AST no greater than 4 times normal
• Bilirubin no greater than 2.0 mg/dL

Renal:

• See Disease Characteristics
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• See Disease Characteristics
• Shortening fraction or ejection fraction at least 40% of normal for age by echocardiogram or radionuclide scan
• No clinically significant comorbid illnesses (e.g., myocardial infarction or cerebrovascular accident)

Pulmonary:

• See Disease Characteristics
• FVC and FEV_1 at least 60% of predicted for age
• DLCO at least 60% of predicted for adults

Other:

• No severe neurosensory symptoms (i.e., peripheral neuropathy)
• HIV negative
• Active infection allowed if controlled by appropriate drug therapy
• Not pregnant or nursing
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• Recovered from prior therapy
• No concurrent investigational agents unless approved by protocol investigators