Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Malignancies or Secondary Myelodysplasia Previously Treated With High-Dose Chemotherapy and Autologous Stem Cell Transplant

RATIONALE: Giving chemotherapy, such as busulfan and fludarabine phosphate, before a 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate, tacrolimus, and antithymocyte globulin before and after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with relapsed hematologic malignancies or secondary myelodysplasia previously treated with high-dose chemotherapy and autologous stem cell transplant .

OBJECTIVES:

Primary

* To demonstrate the efficacy of performing reduced-intensity conditioning allogeneic hematopoietic cell transplantation in patients with relapsed hematologic malignancies or secondary myelodysplasia after completion of prior high-dose chemotherapy and autologous hematopoietic stem cell transplantation.
* To compare the strategy of this regimen with the strategy used in CALGB-100002.

Secondary

* To describe the response rate at 6 and 12 months in patients treated with this regimen.
* To describe the time-to-progression in patients treated with this regimen.
* To determine the ability to use pharmacokinetic-directed busulfan to achieve AUC within 20% of target AUC in \> 80% of patients.
* To determine percent of donor chimerism in T-cell, myeloid and B-cell populations achieved with this regimen compared with CALGB-100002.
* To determine the risk of acute and chronic graft-versus-host disease and other toxicities of this regimen in these patients.
* To describe the overall survival and disease-free survival of patients treated on this regimen.
* To determine the rate of viral, bacterial, and fungal opportunistic infections occurring in the first year after transplantation compared with CALGB-100002.

OUTLINE: This is a multicenter study.

* Preparative Regimen:

  * Busulfan test dose: Patients receive busulfan IV over 45 minutes once during days -14 and -9.
  * Busulfan treatment dose: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV over 3 hours on days -6 to -3.
* Graft-vs-Host Disease (GVHD) Prophylaxis:

  * HLA-identical donor: Patients receive antithymocyte globulin IV over 6-10 hours on days -6 to -5; oral tacrolimus twice daily on days -2 to 90 followed by a taper\* as tolerated until day 150 or 180; and methotrexate IV on days 1, 3, and 6.

NOTE: \* Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is \< 50% at day 60 or patient has progressive disease.

* Matched-unrelated donor: Patients receive antithymocyte globulin, tacrolimus, and methotrexate as in HLA-identical donor regimen. Patients also receive oral mycophenolate mofetil twice daily on days 0 to 60.

  * Allogeneic Stem Cell Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim subcutaneously daily beginning on day 7 and continuing until blood counts recover.
  * Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.

Blood samples are collected at baseline and then periodically during study therapy for pharmacokinetic studies.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for up to 5½ years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed hematologic malignancies:

  * Chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL)

    * Absolute lymphocytosis of \> 5,000/μL
    * Lymphocytes must appear morphologically mature with \< 55% prolymphocytes (CLL)

      * Patients with \> 55% prolymphocytes are considered as having PLL
    * Lymphocyte phenotype with expression of CD20, CD19, and CD5 (CLL)
  * Non-Hodgkin lymphoma

    * Any WHO classification of histologic subtype
    * Core biopsies acceptable for primary diagnosis and immunophenotyping
    * Bone marrow biopsies as sole means of diagnosis not allowed for follicular lymphoma
  * Hodgkin lymphoma

    * Any WHO classification of histologic subtype
    * Core biopsies acceptable for primary diagnosis and immunophenotyping
    * Bone marrow biopsy is required
  * Multiple myeloma

    * Patients must have active disease requiring treatment (Durie-Salmon stage I-III)
  * Acute myeloid leukemia

    * Must have \< 10% bone marrow blasts and no circulating blasts
  * Myelodysplastic syndrome (MDS)

    * MDS as define by WHO criteria
    * Must have \< 10% marrow blasts
* Relapsed or progressive disease or myelodysplasia ≥ 6 months after prior high-dose chemotherapy with autologous hematopoietic cell support

  * Prior syngeneic transplantation allowed
* Healthy donor meeting one of the following criteria:

  * HLA-identical sibling (6/6)

    * Serologic typing for class I (A, B) and molecular typing for class II (DRB1) required
  * 8/8 matched-unrelated donor

    * Molecular identity at HLA A, B, C, and DRB1 by high-resolution typing required
  * No syngeneic donors

PATIENT CHARACTERISTICS:

* Creatinine clearance ≥ 40 mL/min
* Total bilirubin ≤ 2 mg/dL
* AST ≤ 3 times upper limit of normal
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* DLCO ≥ 40% with no symptomatic pulmonary disease
* LVEF ≥ 30% by MUGA or ECHO
* No uncontrolled diabetes mellitus or active serious infection
* No known hypersensitivity to E.coli-derived products
* No HIV infection

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 4 weeks should elapse between prior standard cytotoxic chemotherapy, radiation therapy, or surgery and the planned start of the preparative regimen on day -7