• Disease response at days 30, 60, and 100 following transplant [ Designated as safety issue: No ]
  

• Disease-free survival at 6 months and one year [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the safety and toxicity of a low-intensity nonmyeloablative preparative regimen followed by an allogeneic peripheral blood stem cell transplantation in high-risk patients with hematologic cancer or disease.
• Determine engraftment in patients treated with this regimen.
• Determine the incidence and severity of acute and chronic graft-versus-host disease after the transplantation in these patients.
• Determine the efficacy of controlling hematologic cancers by induction of a graft-versus-tumor effect in these patients.
• Determine the rate of disease-free survival, relapse, transplant-related mortality, and death from all causes in patients treated with this regimen.

OUTLINE: Patients are stratified by risk of graft rejection, which determines the preparative regimen used. High risk is defined as patients with aplastic anemia, those heavily transfused, chemotherapy naive, and single HLA-locus mismatched.

Patients undergo leukapheresis prior to beginning the preparative regimen to collect lymphocytes or leukemia cells for laboratory studies. The cells are studied in the laboratory for graft-vs-malignancy or graft-vs-marrow effect.

Patients then receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1. High-risk patients also receive antithymocyte globulin IV on days -5 to -2.

Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Cyclosporine is administered from day -4 to day 100. Patients with disease progression or donor T-cell chimerism less than 100% after day 100 receive donor lymphocyte infusions up to every 4 weeks until 100% donor T-cell chimerism and/or disease regression is achieved.

Patients are followed at 3 and 6 months, every 6 months for 2.5 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 90 patients (45 per group) will be accrued for this study.

DISEASE CHARACTERISTICS:

Group A

• Any of the following diseases:

  • Chronic myelogenous leukemia in chronic phase
  • Acute lymphoblastic leukemia in complete or partial remission
  • Acute myelogenous leukemia (AML) in first complete or partial remission except for AML with good risk karyotypes: AML M3 t(15;17), AML M4Eo (inv. 16), AML t(8;21)
  • AML in second or subsequent complete remission

  • Myelodysplastic syndromes

    • Refractory anemia with excess blasts (RAEB)
    • RAEB in transformation
    • Chronic myelomonocytic leukemia
  • Myeloproliferative diseases associated with either cytopenia or uncontrolled proliferation
  • Chronic lymphocytic leukemia in complete or partial remission
  • Prolymphocytic leukemia in complete or partial remission
  • Mantle cell lymphoma
  • Lymphoproliferative disorders
  • Viral-associated hemophagocytic syndromes
  • Relapsed Hodgkin's lymphoma
  • Relapsed non-Hodgkin's lymphoma
  • Therapy responsive or stable plateau phase multiple myeloma or extramedullary plasmacytomas AND

  • Age 10 to 55 with high risk for transplant-related complications and mortality due to history of one of the following:

    • Dose-intensive chemotherapy or radiotherapy
    • History of allogeneic or autologous transplantation
    • History of multiple myeloma or extramedullary plasmacytoma
    • Chronic disease or comorbid medical condition, including significant pulmonary, hepatic, kidney, cardiac, or other organ system disease that would result in increased risk of death from a standard myeloablative transplantation

Group B:

• Any of the following diseases:

  • Paroxysmal nocturnal hemoglobinuria associated with life-threatening thrombosis, cytopenia, transfusion dependence, or recurrent debilitating hemolytic crisis (age 8 to 80)
  • Aplastic anemia or pure red cell aplasia associated with transfusion dependence and/or neutropenia and failed immunosuppressive therapy (age 8 to 80)
  • Refractory anemia (RA) or RA with ringed sideroblasts that has failed treatment with antithymocyte globulin or cyclosporine, with transfusion dependence and/or neutropenia (age 8 to 80) AND
  • Curable by allogeneic bone marrow transplantation but high procedural mortality with conventional bone marrow transplantation may delay or prevent this treatment

PATIENT CHARACTERISTICS:

Age:

• 8 to 80

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• See Disease Characteristics
• Bilirubin no greater than 4 mg/dL
• SGOT/SGPT no greater than 5 times upper limit of normal

Renal:

• Creatinine no greater than 2.5 mg/dL

Cardiovascular:

• LVEF at least 30%

Pulmonary:

• DLCO at least 40% predicted

Other:

• Not pregnant or nursing
• No psychiatric disorder or severe mental deficiency
• No other major illness or organ failure
• No other malignant disease liable to relapse or progress within 5 years

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified