• Acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
• Transplant-related mortality [ Designated as safety issue: No ]
• Overall mortality [ Designated as safety issue: No ]
• Leukemic relapse [ Designated as safety issue: No ]
• CMV reactivation and disease [ Designated as safety issue: No ]
• Graft failure [ Designated as safety issue: No ]

• Acute and chronic graft-versus-host disease
• Transplant-related mortality
• Overall mortality
• Leukemic relapse
• CMV reactivation and disease
• Graft failure

RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or stem cell 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 healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing the T cells from the donor cells before transplant and giving cyclosporine before and after the transplant and may stop this from happening. Giving an infusion of the donor's T cells (donor lymphocyte infusion) later may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect).

PURPOSE: This phase II trial is studying how well cyclosporine works in treating patients who are undergoing donor stem cell transplant followed by T-cell add-back (reinfusion) for hematologic malignancies.

OBJECTIVES:

• Determine the effect of peritransplant cyclosporine on donor T-cell chimerism at 30 days post-transplantation in patients with hematologic malignancies undergoing T-cell depleted allogeneic stem cell transplantation followed by T-cell add-back.
• Determine the risk of acute and chronic graft-vs-host disease from T-cell add-back at 60 days post-transplantation in patients treated with this regimen.
• Determine the disease-free survival, relapse, transplant-related mortality, and death from all causes in patients treated with this regimen.
• Determine the cytomegalovirus reactivation in patients treated with this regimen.
• Intensify the preparative regimen for patients with refractory leukemia.

OUTLINE:

• Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2.* Patients undergo total body irradiation twice daily on days -7 to -4.

NOTE: *Patients with high-risk leukemias (marrow blasts > 10% on admission) receive etoposide IV over 4 hours on day -3 and cyclophosphamide IV over 1 hour on day -2.

• Allogeneic stem cell transplantation: Patients undergo T-cell depleted allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
• Graft-versus-host disease (GVHD) prophylaxis: Patients receive oral cyclosporine on days -6 to 21 and days 59 to 120 followed by a slow taper until day 180.
• Donor lymphocyte infusion (DLI): Patients who do not develop significant GVHD receive DLI (T-cell add-back) on day 60 post-transplantation. Patients may receive DLI at any time after transplantation for leukemic relapse, overwhelming viral infection, or suspected graft rejection.

Patients are followed at least weekly up to day 120 post-transplantation, at 6 and 12 months, every 6 months for 1 year, and then annually for at least 3 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes

• Biological: therapeutic allogeneic lymphocytes
• Drug: cyclophosphamide
• Drug: cyclosporine
• Drug: etoposide
• Drug: fludarabine phosphate
• Procedure: allogeneic bone marrow transplantation
• Procedure: peripheral blood stem cell transplantation
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

  • Chronic myelogenous leukemia, including any of the following:

    • In chronic phase, meeting 1 of the following criteria:

      • Under the age of 41 AND no prior treatment with imatinib mesylate
      • Failed prior treatment with imatinib mesylate
      • In accelerated phase or blast transformation

  • Acute lymphoblastic leukemia, including any of the following:

    • Over 18 years of age and in first remission with the following high-risk features:

      • WBC > 100,000/mm^3
      • Karyotypes t9; 22, t4, t19, t11
      • Biphenotypic leukemia
    • Second or subsequent remission, primary induction failure, partially responding, or untreated relapse

  • Acute myeloid leukemia, including any of the following:

    • In first remission [excludes M3 (t15; 17), M4 Eo (inv 16), and t (8; 21)]
    • Second or subsequent remission, primary induction failure, or resistant relapse

  • Myelodysplastic syndromes, including any of the following:

    • Refractory anemia with transfusion dependence
    • Refractory anemia with excess blasts
    • Transformation to acute leukemia
    • Chronic myelomonocytic leukemia

  • Myeloproliferative disorders in transformation to acute leukemia, including any of the following:

    • Myelofibrosis
    • Polycythemia vera
    • Essential thrombocythemia

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

    • Refractory to fludarabine and has bulky progressive disease
    • Thrombocytopenia (platelet count ≤ 100,000/mm^3) OR anemia (hemoglobin ≤ 10g/dL) not due to recent chemotherapy

  • Non-Hodgkin's lymphoma (including mantle cell lymphoma), meeting the following criteria:

    • Relapsing or refractory to current chemotherapy and monoclonal antibody treatment
    • Unsuitable for autologous stem cell transplantation
• Must have an HLA 6/6 identical family donor available

PATIENT CHARACTERISTICS:

Age

• 10 to 55

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin ≤ 4 mg/dL
• Transaminases ≤ 3 times upper limit of normal

Renal

• Creatinine ≤ 3 mg/dL

Cardiovascular

• LVEF ≥ 40%

Pulmonary

• DLCO ≥ 60% of predicted

Other

• HIV negative
• No major organ dysfunction that would preclude transplantation
• No debilitating condition that would preclude intensive myeloablative therapy
• No severe psychiatric illness that would preclude study compliance
• Not pregnant
• 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