Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells

Inclusion Criteria

RECIPIENT

   - Histopathologically-confirmed:

   - Acute leukemia (in first remission with poor risk factors and molecular prognosis)

   - Acute myelogenous leukemia (AML) with -5,-7, t (6;9), tri8, -11

   - Acute lymphoblastic leukemia (ALL) with Ph+ t (9;22), t (4;22), (q34;q11)

   - Acute leukemia with refractory disease or > Complete Remission (CR) 1

   - Chronic myelogenous leukemia (CML) (accelerated, blast or second chronic phase)

   - Myelodysplastic syndrome (in high and high intermediate risk categories)

   - Non-Hodgkin's lymphoma (NHL) with poor risk features and not suitable for autologous
   transplantation

   - Refractory Chronic lymphocytic leukemia (CLL)

   - At least 21 days from the end of most recent prior therapy to start of the transplant
   conditioning regimen

   - Must be < 60 years old at time of registration.

   - Karnofsky Performance Status (KPS) > 70%

Must have related donor who is:

   - Genotypically human leukocyte antigen (HLA) -A, B,C and DR beta 1 (DRB1), DQ loci
   haploidentical to the recipient (but differing for 2 to 3 HLA alleles on the unshared
   haplotype in the graft-versus-host disease (GvHD) direction)

   - No HLA-matched sibling or matched-unrelated donor is identified.

   - Adequate cardiac and pulmonary function (left ventricular ejection fraction (LVEF) >
   45%, diffusing capacity of the lungs for carbon monoxide (DLCO) >50% corrected for
   hemoglobin)

   - Serum creatinine < 1.5 mg/dL OR Creatinine clearance > 50 mL/min for those above serum
   creatinine at least 1.5 mg/dL

   - Serum bilirubin < 2.0 mg/dL

   - Alanine transaminase (ALT) < 2x upper normal limit (ULN) (unless secondary to disease)

   - No prior myeloablative therapy or hematopoietic cell transplantation

DONOR:

   - Age ≤ 70 years

   - Weight ≥ 25 kg.

   - Medical history and physical examination confirm good health status as defined by
   institutional standards

   - Seronegative for HIV Ag within 30 days of apheresis collection for:

   - Hepatitis B surface antigen (sAg) or polymerase chain reaction (PCR) +

   - Hepatitis C ab or PCR+

   - Genotypically haploidentical as determined by HLA typing

   - Female donors (child-bearing potential) must have a negative serum or urine beta-human
   chorionic gonadotropin (HCG) test within 3 weeks of mobilization

   - Capable of undergoing leukapheresis

   - Has adequate venous access

   - Willing to undergo insertion of a central catheter if leukapheresis via peripheral
   vein is inadequate

   - Capable of agreeing to second donation of peripheral blood progenitor cell (PBPC) (or
   a bone marrow harvest) should the patient fail to demonstrate sustained engraftment
   following the transplant

   - Institutional review board (IRB)-approved consent form signed by donor or legal
   guardian > 18 years of age

Donor Selection in the priority order:

   - Recipient's biological mother preferred, if available

   - Other available haploidentical donors will be selected based upon the presence of
   natural killer (NK) alloreactivity between donor and recipient by high-resolution HLA
   typing of the C locus. An NK-alloreactive donor will be preferentially chosen.
   Recipients lacking a killer immunoglobulin-like receptor (KIR)-ligand present in the
   donor along with the corresponding KIR defines "NK alloreactivity".

   - If more than one NK-alloreactive donor is available, preference is to cytomegalovirus
   (CMV)-seronegative donor

Exclusion Criteria

RECIPIENT:

   - Suitable candidate for autologous transplantation or allogeneic transplantation with
   an available matched-related or matched-unrelated donor

   - Seropositive for:

   - HIV ab

   - Hepatitis B sAg or PCR+

   - Hepatitis C ab or PCR+

   - History of invasive Aspergillosis

   - Any active, uncontrolled bacterial, viral or fungal infection

   - Uncontrolled central nervous system (CNS) disease involvement

   - Lactating female

DONOR:

   - Evidence of active infection or viral hepatitis

   - Factors of increased risk for complications from leukapheresis or granulocyte-colony
   stimulating factor (G-CSF) therapy

   - Lactating female

   - HIV-positive