Donor Stem Cell Transplant in Treating Older or Frail Patients With Hematologic Cancer

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or 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 system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and methotrexate and tacrolimus after the transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in treating older or frail patients with hematologic cancer.

OBJECTIVES:

Primary

* Determine the safety of non-myeloablative allogeneic peripheral blood stem cell transplantation, in terms of regimen-related organ toxicity and toxicity from acute graft-vs-host disease (GVHD), in older or medically frail patients with high-risk indolent hematologic malignancies.
* Determine overall survival, disease-free survival, and relapse risk at 1, 2, and 3 years post-transplantation in these patients.

Secondary

* Determine the engraftment of donor hematopoiesis at 6 weeks, 3 and 6 months, and 1 year post-transplantation in these patients.
* Determine the incidence and severity of chronic GVHD in older and medically infirm patients treated with this regimen.
* Determine the safety and efficacy of collecting peripheral blood stem cells from older donors (age \> 60 years).
* Determine the need and efficacy of donor lymphocyte infusions in patients with residual disease after transplant.

OUTLINE:

* Non-myeloablative preparative regimen:Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours every 8 hours on days -4 and -3, and anti-thymocyte globulin IV over 8 hours on days -4 to -1.
* Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover.
* Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus orally every 12 hours or IV continuously beginning on day -2 and continuing until day 90, followed by a taper until day 180. Patients also receive methotrexate IV over 15-30 minutes on days 1, 3, 6, and 11.
* Donor lymphocyte infusions (DLIs): Patients with residual disease ≥ 6 months post-transplantation who are off immunosuppression for ≥ 30 days with no evidence of GVHD may receive DLIs. DLIs are administered ≥ 12 weeks apart in the presence of persistent disease, absence of severe (grade 3-4) GVHD, and absence of persistent GVHD after the first DLI.

After completion of study therapy, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of a high-risk indolent hematologic malignancy meeting the following criteria:

  * Chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria:

    * In second or subsequent remission
    * Failed to achieve a complete remission (CR) after chemotherapy
  * Non-Hodgkin's lymphoma (NHL) meeting 1 of the following criteria:

    * Low-grade NHL meeting 1 of the following criteria:

      * Standard-risk disease in second or subsequent remission
      * Standard-risk disease and failed to achieve a CR after chemotherapy
      * In first or subsequent remission with adverse International Prognostic Index (IPI) prognostic features, as defined by the presence of ≥ 3 of the following:

        * Age \> 60 years
        * Tumor stage III or IV
        * Extranodal disease at \> 1 site
        * ECOG performance status ≥ 2
        * Serum lactic dehydrogenase (LDH) \> upper limit of normal (ULN)
    * Intermediate- or high-grade NHL meeting 1 of the following criteria:

      * In second or subsequent remission
      * Failed to achieve a CR after initial chemotherapy
  * Waldenstrom's macroglobulinemia meeting 1 of the following criteria:

    * In second or subsequent remission
    * Failed to achieve a CR after initial chemotherapy
  * Multiple myeloma meeting 1 of the following criteria:

    * In first or subsequent remission
    * Failed to achieve a CR after initial chemotherapy
  * Myeloproliferative disorders, including any of the following:

    * Chronic myelogenous leukemia in first or subsequent chronic phase
    * Myelofibrosis
    * Essential thrombocytopenia that is poorly responsive to standard therapy
    * Polycythemia vera that is poorly responsive to standard therapy or is in spent phase
  * Prolymphocytic leukemia meeting 1 of the following criteria:

    * In first or subsequent remission
    * Failed to achieve a CR after initial chemotherapy
  * Mantle cell lymphoma meeting 1 of the following criteria:

    * In first or subsequent remission
    * Failed to achieve a CR after initial chemotherapy
  * Hodgkin's lymphoma meeting the following criteria:

    * In second or subsequent remission

      * Prior remission duration \> 6 months
    * No radiation therapy as the only prior primary therapy
  * Myelodysplastic syndromes (MDS) meeting 1 of the following criteria:

    * Refractory anemia with excess blasts (RAEB)
    * RAEB in transformation
    * Chronic myelomonocytic leukemia
    * Any MDS with transfusion dependence
    * Any MDS with ≥ 2 significant infections
  * Acute myeloid leukemia in morphologic remission
* In CR or partial remission or stabilization of disease after standard chemotherapy

  * No progressive or refractory disease
* Not eligible for standard allogeneic bone marrow transplantation
* Meets 1 of the following criteria:

  * Age 60 to 75 years old AND no co-morbid illness
  * Younger patients with any of the following comorbidities:

    * Decreased cardiac ejection fraction
    * Pulmonary dysfunction
    * Elevated liver function tests
    * Hepatitis C infection
    * Poor performance status
* Sibling or related donor available

  * Matched ≥ 5/6 HLA loci (A, B, and DR) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

* See Disease Characteristics
* ECOG performance status 0-2
* Creatinine \< 2.0 mg/dL
* Creatinine clearance \> 40 mL/min
* Ejection fraction \> 30% by echocardiogram or MUGA
* Bilirubin \< 3.0 mg/dL (if total bilirubin is elevated and Gilbert's disease is suspected, direct bilirubin must be normal)
* Alkaline phosphatase \< 4 times ULN
* AST \< 4 times ULN
* HIV negative
* Hepatitis B and/or C virus allowed if a liver biopsy (performed within the past 3 months) shows ≤ grade 2 inflammation
* No active infection

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics