Partially HLA-Mismatched Related Donor Stem Cell Transplant Using Killer Immunoglobulin Receptor and Human Leukocyte Antigen Based Donor Selection in Treating Patients with Hematologic Malignancies

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 risk for relapse including: * t(9;22) or detected BCR-ABL1 translocation by genomic methodologies * BCR-ABL1-Like B-ALL 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) * Central nervous system (CNS) or other extramedullary involvement * White blood cell (WBC) count >= 100,000 cells/uL at diagnosis
• Relapsed ALL, biphenotypic/bilineal leukemia, or acute myeloid leukemia (AML) with =< 10% blasts in the bone 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: * Cytogenetic abnormalities associated with myelodysplastic syndrome including abnormalities of chromosome 5 or 7 * History of anti-neoplastic therapy (radiation or chemotherapy) * Extramedullary involvement * WBC count >= 100,000 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
• Myelodysplastic syndrome, myeloproliferative neoplasms, or myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) overlap syndrome with: * International prognostic scoring system risk score of intermediate (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 Dynamic International Prognostic Scoring System (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. T351I 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 European Society for Blood and Marrow Transplantation (EBMT) consensus criteria
• Patients aged 70-75 with hematopoietic cell transplant-co-morbidity index (HCT-CI) of 0-1 are eligible
• Patients must have Karnofsky performance status >= 70%
• Cardiac left ventricular ejection fraction >= 50% at rest
• Total bilirubin =< 2 mg/dL, except for patient's with Gilbert's syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 x ULN unless thought to be disease related
• Estimated or measured creatinine clearance > 50 mL/min
• Hemoglobin adjusted pulmonary carbon monoxide diffusing capability test (DLCO) >= 50% of predicted, if hemoglobin (Hgb) is within normal range, unadjusted DLCO must be >= 50%
• DONOR: Partially HLA-mismatched relative (allele level matched at 4 to 7 of 8 HLA loci: -A, -B, -C, and -DRB1)
• DONOR: Meets criteria outlined in the Foundation for the Accreditation of Cellular Therapy (FACT)-approved standard operating procedure (SOP) for "DONOR EVALUATION AND SELECTION FOR ALLOGENEIC TRANSPLANTATION" in the Blood and Marrow Transplant Program Manual, document E-1
• DONOR: Donor must be willing to undergo general anesthesia and bone marrow stem cell harvest
• DONOR: Must be >= 14 years old

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 human immunodeficiency virus (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 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 =< 6 treated with curative intent * Non-melanomatous skin cancer
• DONOR: Evidence of infection not responding to antibiotic therapy
• DONOR: Chronic viral infection including active hepatitis B, hepatitis C, HIV, or human T-lymphotropic virus (HTLV)-1/2
• DONOR: Factors that place the donor at increased risk of general anesthesia and bone marrow harvest, such as congenital or acquired bleeding disorders, intolerance or allergy to anesthesia, prior serious surgical complications, or uncontrolled cardiac or pulmonary disorders
• DONOR: Pregnant or breast-feeding
• DONOR: Unwilling or unable to provide informed consent
• DONOR: Unable to provide a bone marrow allograft product