Donor T-cells after Donor Stem Cell Transplant in Treating Patients with Hematologic Malignancies

Inclusion Criteria

• INCLUSION CRITERIA PRIOR TO TRANSPLANT:
• The clinical trial will be offered to all high risk (defined below) patients with hematologic malignancies who require stem cell transplants as part of their standard of care using matched related or unrelated donors
• Patients with high risk myeloid or lymphoid malignancies at stem cell transplant following American Society for Blood and Marrow Transplantation (ASBMT) criteria, including but not limited to conditions listed; these criteria apply BEFORE cyto-reductive therapy given within 28 days of planned conditioning: * Refractory acute myelogenous or lymphoid leukemia * Relapsed acute myelogenous or lymphoid leukemia * Myelodysplastic syndromes with 5% or more blasts * Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase * Recurrent or refractory malignant lymphoma or Hodgkin’s disease with less than a partial response at transplant * High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen * Diseases in response or remission at high risk of relapse at the discretion of the attending physician: some examples include but are not limited to: ** Acute myeloid leukemia (AML) in remission with monosomy 5 or 7, deletion of 5q or 7q, 11q23 mixed-lineage leukemia (MLL) rearrangement or complex karyotype (>= 3 chromosome abnormalities) ** Non-Hodgkin's lymphoma (NHL) in response that is double hit or triple hit (which are characterized by a recurrent chromosome translocation in combination with a v-myc avian myelocytomatosis viral oncogene homolog [MYC]/8q24 breakpoint; these include but not limited to B-cell chronic lymphocytic leukemia [CLL]/lymphoma [BCL]2+/MYC+; BCL6+/MYC+; cyclin D1 (CCND1)+/MYC+; and BCL2+/BCL6+/MYC+) ** Bi-phenotypic lineage leukemia ** CLL with 17p deletion ** Acute lymphoblastic leukemia (ALL) with t(4,11) et al.
• DONORS: Matched related or unrelated donor stem cell transplant (SCT) matched at human leukocyte antigen (HLA) A- B, C, and DRB1 by molecular methods; 7 of 8 matched donor acceptable for related donors
• T-cell depletion with anti-thymocyte globulin (ATG) (rabbit or horse) or at least 30 mg of alemtuzumab total in the conditioning regimen; acceptable conditioning regimens include but are not limited to fludarabine/melphalan/alemtuzumab; fludarabine/busulfan/alemtuzumab; fludarabine/melphalan/ATG; fludarabine/busulfan/ATG
• Immune suppression; planned post-transplant immune suppression should include tacrolimus or cyclosporin monotherapy (i.e., calcineurin inhibitor or CN) for alemtuzumab regimens and a second immune suppressant for ATG treated patients; other agents may be used if CN intolerance or toxicity occurs post-transplant
• Zubrod performance status (PS) 0-2 or equivalent Karnofsky PS
• Eligible for allogeneic transplant in the treating physicians’ judgment and by institutional standards
• ELIGIBILITY TO RECEIVE DLI POST-TRANSPLANT:
• Donor lymphocytes available or able to be collected
• No evidence of disease by standard morphology; minimal residual disease or molecular evidence of disease will not exclude
• Absolute neutrophil count >= 500/ul
• Platelet count >= 20,000/ul without transfusion for 7 days
• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 5 x upper limit of normal (ULN)
• Bilirubin =< 3 x ULN
• No evidence of grade II or higher acute GVHD or chronic GVHD at initiation of first DLI
• No systemic corticosteroids or immunosuppressive drugs (topical acceptable); replacement steroids for adrenal insufficiency are not excluded

Exclusion Criteria

• EXCLUSION CRITERIA PRIOR TO TRANSPLANT:
• Pregnant or lactating females
• Hepatitis B with positive viral load prior to transplant conditioning or hepatitis C virus
• Human immune deficiency virus
• Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent
• Creatinine >= 2.0 mg/dL
• SGOT and SGPT >= 5 x ULN; liver biopsy preferred for such patients
• Bilirubin >= 3 x ULN (unless Gilbert’s syndrome)
• Diffusing capacity of the lung for carbon monoxide (DLCO) < 50% corrected for hemoglobin
• Left ventricular ejection fraction < 40% or equivalent shortening fraction < 20% in pediatric patients
• Unlikely to be able to procure additional donor lymphocytes