Combination Chemotherapy and Donor Stem Cell Transplant in Treating Patients With Aplastic Anemia or Hematologic Cancer

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following:

  • Severe aplastic anemia as defined by either of the following:

    • Marrow cellularity (< 25% [or 25-50% cellularity with < 30% of remaining cells hematopoietic in origin])

    • At least 2 of the following abnormal peripheral blood counts:

      • Reticulocyte count < 1% (corrected for hematocrit)
      • Platelet count < 20,000/mm^3
      • Neutrophil count < 500/mm^3

  • Histologically confirmed hematologic malignancy, including any of the following:

    • Acute leukemia

      • Resistant or recurrent disease after combination chemotherapy with at least one standard regimen OR in first remission and at high risk of relapse
      • Acute myeloid leukemia (AML) (antecedent myelodysplastic syndromes [MDS], secondary AML, or high-risk cytogenetic abnormalities)
      • Acute lymphoblastic leukemia (ALL) (high-risk cytogenetic abnormalities)

    • Chronic myeloid leukemia (CML)

      • Chronic phase, accelerated phase, or blast phase

    • Myeloproliferative disorders or MDS, including any of the following:

      • Myelofibrosis
      • Polycythemia vera*
      • Essential thrombocythemia*
      • Refractory anemia
      • Refractory anemia with excess blasts
      • Refractory anemia with excess blasts in transformation
      • Chronic myelomonocytic leukemia NOTE: * Only if transformed to AML or MDS

    • Lymphoproliferative disease

      • Recurrent or persistent, symptomatic disease after first-line chemotherapy, including any of the following:

        • Chronic lymphocytic leukemia (CLL) (≥ 20% marrow involvement)
        • Waldenstrom macroglobulinemia
        • Low-grade non-Hodgkin lymphoma

    • Intermediate or high-grade non-Hodgkin lymphoma, meeting 1 of the following criteria:

      • Resistant or recurrent disease after combination chemotherapy with one standard regimen
      • Lymphoblastic lymphoma or small noncleaved cell lymphoma in first remission and at high risk of relapse
      • CNS disease
      • Bone marrow disease and LDH greater than 300
  • Solid tumor that would otherwise be treated on RPCI-DS-9115 (or equivalent autologous stem transplant protocol) AND has a syngeneic donor

• Autologous bone marrow transplant not possible (or desirable) due to 1 of the following:

  • History of marrow tumor
  • Inadequate marrow dose
  • Abnormal marrow histology or function prior to storage
  • Thrombocytopenia or leukopenia
  • Marrow cellularity < 20%

• Histocompatible donor identified

  • Well-matched donor, as defined by 1 of the following:

    • Family member matched for 5 or 6 HLA specificities (A, B, DR)*
    • Unrelated donor meeting compatibility criteria of the National Marrow Donor Program (matched for HLA A, B, and DRB1 antigens)*
    • Identical twin sibling
  • If a compatible cord blood donor is identified and there is no suitable unrelated donor available, patient may receive cord blood transplant NOTE: *Patients ≤ 25 years of age may be singly mismatched at the A or B loci

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:

• 4 to 70

Performance status:

• Zubrod 0-2 OR
• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin < 3 times normal (unless due to disease)
• Alkaline phosphatase < 3 times normal (unless due to disease)
• SGOT < 3 times normal (unless due to disease)
• Hepatitis B surface antigen negative
• No severe hepatic disease that would preclude study participation

Renal:

• Creatinine normal
• Creatinine clearance ≥ 50 mL/min
• No severe renal disease that would preclude study participation

Cardiovascular:

• Cardiac ventricular ejection fraction ≥ 50% by MUGA or echocardiogram
• No uncontrolled or severe cardiovascular disease (e.g., myocardial infarction, congestive heart failure, symptomatic angina, life threatening arrhythmia, or hypertension within the past 6 months)

Pulmonary:

• DLCO or DLVA ≥ 50% predicted (corrected for hemoglobin or alveolar ventilation)

Other:

• No serious concurrent medical or psychiatric illness

• No other serious organ dysfunction (unless due to underlying disease), including the following:

  • Uncontrolled bacterial, viral, or fungal infection
  • Uncontrolled peptic ulcer disease
  • Uncontrolled diabetes mellitus
• HIV negative
• Cytomegalovirus status known
• Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• Pretransplant cytoreductive chemotherapy allowed for patients with relapsed or refractory disease

Endocrine therapy:

• Not specified

Radiotherapy:

• Not eligible for total-body irradiation if prior radiotherapy exceeded the following limits:

  • Mediastinum: 3,600 cGy
  • Heart: 3,600 cGy
  • Whole lungs: 1,200 cGy
  • Small bowel: 3,600 cGy
  • Kidneys: 1,200 cGy
  • Whole liver: 1,600 cGy
  • Cranial spinal: 3,600 cGy
  • Brain: 4,000 cGy
  • Retina: 4,000 cGy

Surgery:

• Not specified