Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant

RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop 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, and antithymocyte globulin before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects of giving sirolimus together with tacrolimus and antithymocyte globulin and to see how well it works in preventing graft-versus-host disease in patients with hematologic cancer who are undergoing donor stem cell transplant.

OBJECTIVES: Primary * To determine the incidence and severity of acute graft-versus-host disease (GVHD) after HLA-matched or -mismatched unrelated donor peripheral blood stem cell transplantation (PBSCT) in patients with hematologic malignancies treated with immunosuppressive therapy comprising sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD prophylaxis. * To determine the safety of this regimen in these patients at 6 months after PBSCT. Secondary * To determine the time to engraftment (i.e., platelet and absolute neutrophil recovery) in patients treated with this regimen. * To determine the length of hospital stay of these patients within 100 days after PBSCT. * To determine the incidence of infections, including CMV and EBV reactivation and post-transplant lymphoproliferative disorders, in patients treated with this regimen. * To determine the incidence of thrombotic microangiopathy and veno-occlusive disease in patients treated with this regimen. * To determine the incidence of chronic GVHD in patients treated with this regimen. * To determine the overall and disease-free survival of these patients at 2 years after PBSCT. * To determine the Karnofsky performance status of these patients at baseline and at various time points after PBSCT. * To conduct immunocorrelative studies prior to and at various time points after PBSCT. OUTLINE: * Conditioning regimen: Patients receive 1 of 6 conditioning regimens (standard of care treatment) between days -9 and -3, based on diagnosis and the treating physician's preference regarding regimen intensity. * Regimen I: Patients receive fludarabine phosphate IV and busulfan IV. * Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV. * Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV. * Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV. * Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV. * Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI. * Allogeneic peripheral blood stem cell transplantation: Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0. * Graft-versus-host disease prophylaxis (GVHD): Patients receive tacrolimus IV continuously over 24 hours or orally and sirolimus orally beginning on day -3 and continuing until day 30 or day 90, followed by a taper in the absence of GVHD. Patients also receive anti-thymocyte globulin IV over 4-8 hours on days -3 to -1. Blood samples are obtained at baseline and periodically during study for correlative biomarker studies. Samples are analyzed by T-cell immunophenotyping, absolute subset number quantification, and multi-parameter flow cytometry for evaluation of immune reconstitution, T-cell differentiation status, NK-cell recovery, allo-reactivity of donor T-cells after transplantation, and regulatory T-cell reconstitution. After completion of study therapy, patients are followed periodically for up to 2 years.