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