Post Transplant Donor Lymphocyte Infusion
Condition: Leukemia, Myeloid, Chronic; Lymphomas; Multiple Myeloma; Myelodysplastic Syndrome; Leukemia, Lymphocytic, Acute; Leukemia, Lymphocytic, Chronic; AML
MeSH terms: Leukemia; Multiple Myeloma; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes
Intervention: Donor Lymphocyte Infusion; Induction Chemotherapy
Intervention description: donor cells infused over 2 hrs at cell dose of 0.5 dx 10^8 CD3+T-cells/kg; Fludarabine 25 mg/m2 IV Cyclosphosphamide 60 mg/kg IV
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 1 Year
Maximum age: 70 Years
Healthy volunteers: No
Keywords: donor lymphocyte infusions; BMT; bone marrow transplant

Summary:

      The purpose of this study is to test the hypothesis that a pre-infusion preparative regimen
      of cyclophosphamide and fludarabine will improve the effectiveness of DLI in patients with
      blood cancers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients (age > or = 1 years) with a diagnosis of relapse after related or unrelated
             allogeneic stem cell transplantation for a hematological malignancy.

          -  For CML, relapse will be defined as any cytogenetic evidence of a Philadelphia
             chromosome or persistence of BCR/ABL rearrangements by molecular testing on at least
             two measurements over a 6 month interval. If cytogenetics are normal and there is PCR
             evidence of a BCR/ABL fusion, patients will be eligible if they have evidence of a
             quantitative increase in CML measured either by quantitative PCR or by fluorescent in
             situ hybridization (FISH).

          -  For non-CML, relapse will be defined based on disease specific morphologic criteria
             from a bone marrow biopsy and aspirate or recurrence of disease specific cytogenetics.
             For disease specific definition of relapse, see appendix 3. Relapse can be determined
             morphologically with less than 5 percent blasts if definitive relapse can be
             determined. Equivocal results for relapse should result in a repeated test after an
             appropriate time interval (suggested 1 month) to determine eligibility.

        Post-transplant lymphoproliferative diseases (often referred to as EBV-associated
        lymphomas) are NOT eligible for this protocol.

          -  For Chronic Phase CML patients only

          -  - must have failed (no response in 3 months or incomplete response at 6 months) or
             refused treatment with Gleevec

          -  - if no prior DLI, CML patients will first have DLI- if relapse occurs after DLI, DLI
             with chemotherapy per this protocol will be offered

          -  Patients must be within one year of identification of relapse or if beyond that time
             period, must have at least 10% donor DNA by RFLP or cytogenetics.

          -  Same allogeneic donor (sibling or URD) used for transplantation is available for
             lymphocyte donation.

          -  No severe organ damage (by laboratory or clinical assessment) as measured by:

          -  - blood creatinine ≤ 2.0 mg/dL

          -  - liver function tests < 5 x normal

          -  - left ventricular ejection fraction > 40% (testing required only if symptomatic or
             prior known impairment).

          -  - pulmonary functions > 50% (testing required only if symptomatic or prior known
             impairment). Oxygen saturation (>92%) can be used in child where PFT's cannot be
             obtained.

          -  - chest x-ray without evidence of active infection

          -  Off prednisone and other immunosuppressive agents (given for any reason) for at least
             3 days prior to DLI infusions.

          -  Performance status ≥ 60%

          -  Women must not be pregnant or lactating. The agents used in this study may be
             teratogenic to a fetus and there is no information on the excretion of agents into
             breast milk All females of childbearing potential must have a blood test or urine
             study within 2 weeks prior to registration to rule out pregnancy

          -  Women of childbearing potential and sexually active males are strongly advised to use
             an accepted and effective method of contraception

          -  Patient must given written informed consent indicating understanding of the nature of
             the treatment and its potential risks

        Exclusion Criteria:

          -  Concurrent signs of acute or chronic graft-versus-host disease requiring ongoing
             treatment at the time of relapse will be ineligible.

          -  Patients being treated for GVHD with prednisone, cyclosporine, Imuran or other
             immunosuppressive medications are not eligible until these medications are
             discontinued for at least 2 weeks without a flare of GVHD.

          -  Active CNS leukemia

          -  Active fungal infection or pulmonary infiltrates (stable prior treated disease is
             allowable)

          -  HIV positive