Early Administration of ATG Followed by Cyclophosphamide, Busulfan and Fludarabine Before a Donor Stem Cell Transplant in Patients With Hematological Cancer

RATIONALE: Giving low doses of chemotherapy before a donor 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 antithymocyte globulin before the transplant and tacrolimus and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving antithymocyte globulin together with cyclophosphamide, busulfan, and fludarabine works in treating patients with hematological cancer or kidney cancer undergoing donor stem cell transplant.

OBJECTIVES:

* To assess the percentage of patients with hematological malignancies or renal cell carcinoma who achieve \> 90% donor T-cell chimerism at 30 days after treatment with reduced-intensity conditioning comprising low-dose anti-thymocyte globulin, low-dose cyclophosphamide, busulfan, and fludarabine phosphate followed by allogeneic peripheral blood progenitor cell transplantation from a matched related donor.
* To assess the incidence of severe (grade 3 or 4) acute graft-versus-host disease (GVHD) and extensive chronic GVHD in these patients.
* To assess whether this regimen is associated with reduced transplant-related toxicity and increased tolerability in these patients.
* To assess the overall safety of this conditioning regimen as measured by 6-month transplant-related mortality in these patients.
* To determine the efficacy of this regimen in inducing durable remissions in these patients.

OUTLINE:

* Reduced-intensity conditioning (RIC): Patients receive anti-thymocyte globulin IV over 4-6 hours on day -16 and over 6-8 hours on day -15, fludarabine phosphate IV over 30 minutes on days -7 to -3, busulfan IV over 3 hours on days -4 and -3, and cyclophosphamide IV over 1-2 hours on day -2.
* Transplantation: Patients undergo allogeneic peripheral blood progenitor cell transplantation on day 0.
* Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral tacrolimus every 12 hours on days -1 to 90, followed by a taper until day 150. Patients also receive methotrexate IV on days 1, 3, and 6.

Blood samples are collected periodically for pharmacokinetic studies of anti-thymocyte globulin and PCR analysis for chimerism.

After completion of study therapy, patients are followed periodically for up to 3 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed diagnosis of one of the following:

  * Chronic myeloid leukemia (CML)

    * Philadelphia chromosome (Ph)- and/or BCR-ABL-positive disease
    * In chronic or accelerated phase
    * Suboptimal response to imatinib mesylate (i.e., no hematologic complete response by 3 months, no major cytogenetic response by 6 months, or no complete cytogenetic response by 1 year)
    * CML in blastic transformation allowed provided patient achieved complete remission (CR) or second chronic phase after treatment with imatinib mesylate or chemotherapy
  * Chronic lymphocytic leukemia meeting one of the following criteria:

    * Rai stage III or IV disease
    * Rai stage I or II disease that failed standard therapy (i.e., disease is progressing after ≥ 1 course of standard therapy)
  * Non-Hodgkin lymphoma (NHL) meeting one of the following criteria:

    * Indolent NHL

      * Clinical stage III or IV disease or bulky stage II disease (i.e., ≥ one lymphoid mass \> 5 cm in ≥ one dimension)
      * Relapsed after primary therapy OR is refractory to therapy
    * Aggressive NHL

      * Is not considered curable with standard chemotherapy or autologous stem cell transplantation (i.e., relapsed after autologous stem cell transplantation)
      * Chemotherapy-responsive disease
  * Multiple myeloma

    * Durie-Salmon stage II or III disease

      * Durie Salmon stage I disease allowed provided β2 microglobulin level \> 3 mg/dL
  * Acute myeloid leukemia or acute lymphocytic leukemia

    * In CR (defined as \< 5% blasts in bone marrow and no circulating blasts) AND has any of the following poor prognostic features:

      * WBC \> 100,000/mm\^3 at presentation
      * In second or greater remission
      * Adverse-risk cytogenetics (i.e., Ph1-positive, 11q23 translocation, -5, -7, complex translocations, or other recognized adverse-risk cytogenetics)
  * Renal cell carcinoma

    * Stage IV disease
    * Clear cell morphology
  * Myelodysplastic syndromes

    * Bone marrow blasts ≤ 10% on last bone marrow biopsy prior to transplantation
  * Myeloproliferative disease

    * Anticipated life expectancy on conventional therapy \< 10 years
    * No uncomplicated essential thrombocythemia or primary polycythemia
  * Hodgkin lymphoma

    * Relapsed after ≥ 1 standard-dose chemotherapy regimen
    * Not considered curable by autologous stem cell transplantation
* No clinical evidence of active CNS involvement

  * Previously treated leptomeningeal disease allowed provided CSF cytology is negative at the time of assessment for transplantation
* Available 6/6 allele match (i.e., HLA-A, B, DRβ1)matched related donor

PATIENT CHARACTERISTICS:

* ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
* Bilirubin \< 3 times normal (unless abnormality due to malignancy)
* AST and ALT \< 3 times normal (unless abnormality due to malignancy)
* Creatinine ≤ 2.0 mg/dL
* LVEF ≥ 40% by MUGA or ECHO
* DLCO ≥ 40% of predicted
* FEV-1 ≥ 50% of predicted
* Not pregnant or nursing
* Fertile patients must use effective contraception
* Deemed to be an appropriate candidate for allogeneic SCT
* No evidence of myocardial infarction within the past 6 months
* No psychological or social condition that may interfere with study participation
* No serious uncontrolled localized or active systemic infection
* No second malignancy within the past 3 years except for completely excised nonmelanotic skin cancer or in situ carcinoma of the cervix
* No chronic inflammatory disorder requiring the continued use of glucocorticoids or other immunosuppressive medications
* No known HIV positivity
* No hypersensitivity to E. coli-derived proteins