RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .

OBJECTIVES:

Primary

• To determine the incidence and severity of acute- and chronic-graft-versus-host disease (GVHD) after HLA-matched or -mismatched unrelated donor hematopoietic peripheral blood transplantation in patients with hematologic malignancies scheduled to receive immunosuppressive combination of sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD prophylaxis.
• To determine the safety of this combination in the first six months post-transplant.

Secondary

• To determine the time-to-engraftment, non-relapse mortality rate, overall and disease-free survival, incidence of disease relapse, and incidence of opportunistic infections with this GVHD prophylaxis.

OUTLINE: Patients are stratified according to conditioning regimen (fludarabine phosphate and melphalan vs fractionated total-body irradiation [FTBI] and etoposide vs FTBI and cyclophosphamide) and degree of donor/recipient HLA mismatch (high-risk vs low-risk).

• Conditioning regimen: Patients receive 1 of 3 standard conditioning regimens beginning on day -9 or -8 and continuing to day -1 or 0.
• Peripheral blood stem cell transplantation: Patients receive HLA-matched or mismatched unrelated donor peripheral blood stem cells on day 0.
• Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously beginning on day -3 and then orally when tolerated, oral sirolimus on days -3 and -2, anti-thymocyte globulin IV over 4-8 hours on days -3 to 0, and methotrexate* IV on days 1, 3, and 6. Tacrolimus and sirolimus continue for 3-6 months (with taper).

NOTE: *Only patients with high-risk HLA mismatch receive treatment with methotrexate.

After completion of study therapy, patients are followed periodically for up to 2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of hematological malignancy including any of the following:

  • Non-Hodgkin lymphoma (NHL) in any complete remission (CR) or partial response (PR)

  • Hodgkin lymphoma in any CR or PR

  • Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in any CR

    • Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood absolute blast count < 500/µL on the day of initiation of conditioning for patients with non-CR AML or ALL

  • Myelodysplastic syndromes (MDS) treated or untreated

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

  • Multiple myeloma in any CR or PR

  • Chronic lymphocytic leukemia in CR or PR 2 or greater

  • Myelofibrosis and other myeloproliferative disorders

    • Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood absolute blast count < 500/µL on the day of initiation

• High-risk disease defined as AML or ALL > CR1, accelerated phase CML, recurrent aggressive lymphoma, or active lymphoproliferative disease at transplant

• Low-risk disease defined as AML or ALL in CR1, chronic phase CML, or low-grade lymphoproliferative disorder with controlled disease at transplant

• Must be planning to receive 1 of the following conditioning regimens at City of Hope:

  • Fludarabine phosphate and melphalan for patients with hematological malignancies and contraindications for conventional myeloablative regimens due to age, co-morbidity, or previous transplant
  • Fractionated total-body irradiation (FTBI) and etoposide for patients with AML and ALL or CML in accelerated phase
  • FTBI and cyclophosphamide for patients with NHL, AML, CML, and MDS

• Suitable unrelated donor available

  • HLA-matched or mismatched
  • Peripheral blood stem cells available
  • No bone marrow or ex vivo-engineered or processed graft (e.g., CD34-positive, T-cell depletion)

• No uncontrolled CNS disease

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 70-100% or ECOG PS 0-2
• Creatinine < 1.3 mg/dL or creatinine clearance ≥ 70 mL/min
• Ejection fraction > 45%
• Direct bilirubin < 3 times upper limit of normal (ULN)
• ALT and AST < 3 times ULN
• Forced vital capacity, FEV1, and DLCO > 45% of predicted
• Able to cooperate with oral medication intake
• No active donor or recipient serology positive for HIV
• No known contraindication to administration of sirolimus, tacrolimus, or anti-thymocyte globulin
• No active hepatitis B or C
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent participation in other clinical trials for prevention or treatment of viral, bacterial, or fungal disease allowed provided agents do not interact with agents used in the current study