Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia

Inclusion Criteria: * Patients must have a histologically and cytological confirmed acute myeloid leukemia, high risk AML defined as: * Age \> 60, or * Presence of complex cytogenetic abnormalities (with \> 3 cytogenetic abnormalities), del (7q, -5, -7), t(9,22), 11q(23) or high risk mutations by FISH eg MLL, FLT-3 + * Secondary AML, or * A white blood cell count of \> 50 x10\^9/L * Patients must be medically ineligible for allogeneic stem cell transplant (alloSCTx) or not have a known fully HLA matched sibling for planned sibling transplant. * Patients must have measurable or evaluable disease * Diagnosis of AML according to World Health Organization (WHO) diagnostic criteria (at least 20% blasts in the peripheral blood or bone marrow), with French-American-British Cooperative group (FAB) classification other than M3 (acute promyelocytic leukemia), documented by bone marrow aspiration and biopsy performed within 14 days prior to administration of 1st dose of remission induction chemotherapy; if a bone marrow aspirate and biopsy were obtained within 28 days prior to the first dose of remission induction therapy then these tests may be submitted for review at University of Southern California (USC) and a repeat screening bone marrow does not need to be conducted; * Cohort A: newly diagnosed AML, no prior cytotoxic chemotherapy * Cohort B: newly diagnosed AML, failed to achieve Complete remission (CR) with single standard Induction chemo. * Patient has at least one medically fit family member expected to be HLA mismatched at 1-9/10; more commonly and preferred: 4-6/10 loci (parent, sibling, niece/nephew, etc but adult children preferred) * Absolute neutrophil count (ANC) \> 1500, unless due to direct bone marrow involvement of disease * Platelets \> 75,000, unless due to direct bone marrow involvement of disease * Hemoglobin \> 8.0 gm/dL, transfusion allowed * Serum creatinine \< 2.0 x the upper limits of institutional normal (ULN) * Total bilirubin \< 1.5 x the upper limits of institutional normal * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT )\< 2.5 x the upper limits of institutional normal (=\< 5 x ULN for patients with liver involvement of leukemia) * Cardiac left ventricular ejection fraction (LVEF) \> 45% * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Estimated survival of at least 3 months * Patients must be able to understand and agree to sign an Institutional Review Board (IRB)-approved informed consent form * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study, and for two months after study participation * DONOR: Donor screening; all donors will meet the standard blood donor criteria established by the participating local blood center, American Association of Blood Banks (AABB) * DONOR: Donors will be selected from among the subject's relatives, adult children preferred * DONOR: Infectious disease testing will be done per Hemacare policy and AAAB guidelines * DONOR: Donor and intended recipient red cell type and compatibility will be determined * DONOR: Donors will be pre-selected on the basis of HLA haploidentity * DONOR: If patient is cytomegalovirus (CMV)-negative, donors who are CMV-negative will be preferred; CMV serology of the donor will be tested prior to the allogeneic cell donation; donations from CMV-positive donors to CMV-negative recipients will be given if no CMV negative donor is available, and CMV surveillance and pre-emptive treatment given Exclusion Criteria: * Cohort A: Patients who have received prior cytotoxic chemotherapy, such as anthracyclines and cytarabine not permitted; but prior treatment with demethylating agents (azacytidine or decitabine, lenalidomide, etc) ALLOWED. * Cohort B: Patients who have received prior fludarabine, clorarabine or drugs known to target T cells not permitted; but prior standard induction with anthracylines and cytarabine ALLOWED including after demethylating agents. * Have uncontrolled systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular or respiratory systems * Pregnant and/or lactating * Patients who have had non-biopsy surgery in the last 10 days * Active central nervous system (CNS) disease; patients with previously treated leptomeningeal disease without evidence of remaining leukemia cells by spinal fluid will be eligible * Known active autoimmune disorder * Known to be human immunodeficiency virus (HIV)-positive or have active hepatitis B or C * Patients concurrently taking the following drugs are excluded: mycophenolate, cyclosporine, prednisone \> 20mg/day, or immunosuppressive agents * DONOR: Personal or family history of severe sickle cell disease or variant (unless donor has tested negative); testing for the presence of hemoglobin S is not required * DONOR: Positive infectious disease test as dictated by blood collection center's standard operating procedure (SOP) * DONOR: Current uncontrolled hypertension * DONOR: Diabetes mellitus * DONOR: Active peptic ulcer disease * DONOR: Pregnant or breast-feeding * DONOR: Currently taking lithium therapy * DONOR: History of autoimmune disease * DONOR: History of coronary disease