Inclusion Criteria:

• Patients </= 50 years of age meeting standard performance and end-organ function criteria for stem cell transplantation.
• Cardiac function: left ventricular ejection fraction > 45%
• Renal function: Serum creatinine < 2x upper limit of normal for age or if serum creatinine elevated beyond normal, must have creatinine clearance or glomerular filtration rate > 50% lower limit of normal for age
• Hepatic function: AST/ALT < 3x upper limit of normal for age and bilirubin < 2.0 mg/dl. These criteria do not apply if liver is involved with disease.
• Pulmonary function: Patient must have room air O2 saturation >95% and no clinical evidence of pulmonary insufficiency unless the lungs are involved with disease.
• Patients with acute myelogenous leukemia (AML): induction failure with < 3 induction courses, >/= second or greater complete remission (CR) (defined as <5% blasts in bone marrow and no active extramedullary disease) , CR1 with high risk features defined as history of induction failure, 5q- or monosomy 7 cytogenetic findings;
• Patients wih acute lymphocytic leukemia (ALL): >/= second or greater CR (defined as <5% blasts in bone marrow and no active extramedullary disease), CR1 with high risk features defined as history of induction failure or Ph+ or t(4;11) on cytogenetic analysis or any infant with MLL rearrangements on cytogenetic analysis;
• Patients with myelodysplastic syndrome (MDS): refractory anemia (RA) with excess blasts (EB) with intermediate (INT)-1, INT-2 or high International Prognosis Score System (IPSS) score, RAEB in transformation (iT) with INT-1, INT-2 or high IPSS score and patients with RA and INT-2 IPSS score
• Patients lacking a suitably matched family donor defined by genotypic or phenotypic identity for >/= 5/6 A, B, DR loci
• Patients lacking an immediately available genotypically matched (6/6) unrelated marrow donor or umbilical cord blood donor with suitable cell dose after a search of greater than or equal to 2 months OR patients whose medical condition is at high risk of deteriorating or whose disease is at high risk of progression during a donor search
• Patients must have a healthy family member donor who must be at least genotypically HLA-A, B, C, DR haploidentical to the patient.
• Donors must sign voluntary, written informed consent OR in the case of minor donors such consent must be signed by the parent or guardian and assent will be requested as age appropriate.
• Donors must be capable of undergoing leukapheresis, have adequate venous access and be willing to undergo placement of a central venous catheter should leukapheresis via peripheral access be inadequate.
• Note that satisfactory mobilization of donor peripheral blood stem cells (PBSC) to meet protocol criteria must take place prior to initiation of conditioning of the patient.
• Donors must be informed that they would be requested to undergo a second donation of PBSC or a BM harvest should the patient fail to demonstrate sustained engraftment after HSCT
• Donors must meet all the medical criteria for blood product donation, including negative test for HIV, freedom from other active infection, absence of medical condition posing a health risk to donation of PBSC or function of the graft.
• To provide a source of peripheral blood mononuclear cells to serve as allosensitizers patients must EITHER: (a) have a parent disparate with the donor for the haplotype shared by the patient and parent but not shared by the patient and donor; OR (b) be able to donate sufficient autologous cells by peripheral blood draw or unstimulated leukapheresis
• Female patients of child-bearing age must have a negative pregnancy test and be using an form of contraception considered effective and medically acceptable by the investigator.
• Voluntary written informed consent. Children will be asked for assent wherever age appropriate.

Exclusion Criteria:

• Active infection. Freedom from active infection is defined as: absence of an infectious diagnosis or (in patients who have had a recent positive infectious diagnosis) the resolution of fever, documentation of negative cultures or antigen testing, continuation or completion of a course of appropriate therapy, and presence of stable to resolving clinical symptoms.
• Evidence of HIV infection or known HIV positive serology
• Presence of active CNS disease
• ALL patients who relapse with isolated extramedullary disease after completion of treatment
• Any prior stem cell transplant