Haploidentical (Half-matched) Related Donor Stem Cell Transplantation Using Killer Immunoglobulin-like Receptors in Addition to Normal Selection Factors to Determine the Best Donor

Inclusion Criteria:

Patients with any of the following hematologic malignancies who are considered to be
eligible for allogeneic transplantation:

- Acute lymphoid leukemia (ALL) in first complete remission (CR1) with high riskfor
relapse including:

- t(9;22) or detected BCR-ABL1 translocation by genomic methodologies

- BCR-ABL1-Like B-ALL [54] including mutations of IKZF1 or CRLF2

- Translocations or mutations involving 11q23 (MLL) gene.

- Hypodiploid karyotype

- Deletion of 9p

- Loss of 17p or TP53 mutation

- T-lymphocyte lineage antigen expression (T-ALL)

- CNS or other extramedullary involvement

- WBC count >/= 100,000 cells/μL at diagnosis

- Relapsed ALL, biphenotypic/bilineal leukemia, or AML with marrow prior to transplantation

- Acute biphenotypic or bilineal leukemia in first or greater complete remission.

- Acute myeloid leukemia (AML) in CR1 with intermediate or high risk features including:

- Cytogeneic abnormalities associated with myelodysplatic syndrome including
abnormalities of chromosome 5 or 7

- History of anti-neoplastic therapy (radiation or chemotherapy)

- Extramedullary involvement

- WBC count >/= 100,00 cells/ul at diagnosis

- Rearrangements or mutations of 11q23 (MLL)

- Abnormalities of chromosome 3

- TP53 mutation or loss of 17p

- Complex or monosomal karyotype

- Normal karyotype with mutations of FLT3, RUNX1, or ASXL1

- Myleodysplastic syndrome, myeloproliferative neoplasms, or MDS/MPN overlap syndrome
with:

- International prognostic scoring system risk score of INT-2 or high risk at the time
of transplant evaluation

- Any risk category if life-threatening cytopenia exists

- Karyotype or genomic changes that indicate high risk for progression to acute
myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53,
or complex or monosomal karyotype

- Myelofibrosis with DIPSS scores of INT-2 or high risk or any risk category if life
threatening cytopenias are present

- Chronic myelomonocytic leukemia (CMML)

- Chronic myeloid leukemia (CML) who have failed or are intolerant to BCR-ABL tyrosine
kinase inhibitors

- CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition
(e.g. T351 l mutation)

- CML with accelerated or blast phase with <20% blasts after therapy

- Hodgkin lymphoma:

- Relapsed disease with progression after autologous bone marrow transplant or are
ineligible for this procedure

- Responding to therapy prior to enrollment

- Non-Hodgkin lymphoma:

- Responding to therapy prior to enrollment

- Progression after autologous bone marrow transplant or are ineligible for this
procedure

- Chronic lymphocytic leukemia with high risk disease as defined by the EBMT consensus
criteria

- Patients aged 18 through 69 years old are eligible

- Patients aged 70-75 with HCT-CI of 0-1 are eligible

- High risk hematologic malignancies

- Patients must have Karnofsky performance status >/= 70%

- Cardiac left ventricular ejection fraction >/= 50% at rest

- Total bilirubin
- AST and ALT
- Estimated or measured creatinine clearance > 50 mL/min

- Hemoglobin adjusted pulmonary DLCO >/= 50% of predicted

Exclusion Criteria:

- Persons with a HLA matched sibling donor.

- Female patients who are pregnant or breast-feeding

- Persons with an infection that is not responding to antimicrobial therapy

- Persons who are seropositive for HIV.

- Persons with uncontrolled central nervous system malignancy •Persons who do not meet
the age and organ function criteria specified above Presence of psychiatric or
neurologic disease, or lack of social support that limits the patient's ability to
comply with the treatment protocol including supportive care, follow-up, and research
tests.

- Prior diagnosis of non-hematologic malignancy within 5 years of planned protocol
therapy EXCEPT:

- Diagnosis of breast ductal carcinoma in situ treated with curative intent

- Diagnosis of prostate adenocarcinoma with Gleasons score curative intent

- Non-melanomatous skin cancer