The primary objectives are the following:

• To assess the safety of infusing alloreactive NK cells from a haploidentical relative and to determine the maximum tolerated dose of these cells given in combination with busulfan, fludarabine, Thymoglobulin and allogeneic transplantation from a separate HLA identical donor for treatment of AML/MDS.
• To determine the rate of engraftment, graft-vs-host disease (GVHD), immune reconstitution and survival after infusion of alloreactive haploidentical NK cells effects.

NK cells are part of the immune system (the cells in your body that fight disease). Sometimes, NK cells react against and fight leukemia cells that are mismatched with your body for certain HLA tissue type proteins. When the NK cells react, these cells are called "alloreactive NK cells."

In this study, researchers will collect alloreactive NK cells from the blood of a relative of yours whose HLA proteins do not match yours exactly. The NK cells are separated from the blood using a machine called a CLINIMACs system. This machine uses special kinds of cells and magnetic beads to separate the NK cells. The drug interleukin-2 is then added to the NK cells, to improve their function. The interleukin-2 will be washed out of the cell sample before it is given to you. The CliniMACS System is a medical device that is used to separate types of blood cells from blood that is removed from the body during leukapheresis. These separated cells are processed for use in treatments such as stem cell transplants.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have routine blood tests (about 4 tablespoons) and urine tests performed, and a bone marrow biopsy will also be performed. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. You will have a chest x-ray, an electrocardiogram (ECG--a test to measure the electrical activity of the heart), and either a Multi-gated Acquisition (MUGA) scan or an echocardiogram (ECHO) to test the function of your heart. A MUGA scan uses a liquid that is injected into your vein that travels through your heart during the scan, while an ECHO uses sound waves to check heart function. You will have a lung function test performed. Women who are able to have children must have a negative blood pregnancy test before starting treatment.

If you are still able to take part in this study, you will receive high-dose chemotherapy for 4 days. You will receive fludarabine over about 30 minutes daily as an intravenous (IV--through a needle in your vein) infusion. You will also receive busulfan over 3 hours by IV once a day. About 2 days later, you will be given the infusion of the alloreactive NK cells by IV. Patients will receive one of 3 dose levels. Some patients will receive interleukin-2 daily for 4 days.

Five (5) days after the NK cell infusion, thymoglobulin will be given to you by IV daily for 3 days. Thymoglobulin is an immunosuppressive treatment to reduce the risk of graft rejection. Then blood stem cells will be administered IV from a different stem cell donor whose HLA type matches yours.

You will receive the drugs tacrolimus and methotrexate to help lower the risk of a reaction called "graft-vs.-host disease" (GVHD). GVHD is when the donated immune cells in the transplant react against the body of the person receiving the cells. Tacrolimus will be given by IV for about 2 weeks, and after that it is given by mouth as a pill for at least 3 months. Methotrexate will be given as an IV injection for 3 to 4 doses over the first 11 days after the stem cell transplant.

You will also receive the drug G-CSF (Neupogen) as an injection under the skin until your blood cell counts reach a certain high enough level.

You will need to stay in the hospital for about 4 weeks. After you leave the hospital, you will continue as an outpatient in the hospital area, which means you will have to stay close enough to be able to come back for any visits for at least 100 days after the transplant.

You will be asked to come back to the clinic at 3, 6, and 12 months after your transplant for routine safety testing. This will include a physical exam, a bone marrow biopsy, and routine blood draws.

This is an investigational study. The way the researchers make the alloreactive NK cells using the CLINIMACs device is investigational. These cells will be provided free of charge. The CliniMACS device is not FDA approved. At this time, it is being used in research only. Up to 18 patients will take part in this study.

• Myelodysplastic Syndrome
• Leukemia

• Drug: Thymoglobulin
• Drug: Busulfan
• Drug: Fludarabine

Inclusion Criteria:

1. Patients with age </= 70 years with one of of the following: Acute myeloid leukemia past first remission, in first or subsequent relapse, in second or greater remission or primary induction failure; Myelodysplastic syndromes with intermediate or high risk IPSS score; CML which has progressed to accelerated phase or blast crisis despite imatinib treatment
2. Patients must have an HLA matched related or unrelated donor willing to donate for allogeneic peripheral blood progenitor cell transplantation.
3. Patients must have a haploidentical relative who is predicted to be alloreactive based upon the presence of the relevant KIR genes and incompatibility with the recipient for HLA C and Bw antigens.
4. Zubrod performance status </= 2.
5. Left ventricular ejection fraction >/= 45%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
6. No symptomatic pulmonary disease. FEV1, FVC and DLCO >/= 50% of expected, corrected for hemoglobin.
7. Serum creatinine </= 1.8mg%.
8. SGPT </= 200 IU/ml unless related to patients malignancy.
9. Bilirubin </= 1.5 mg/dl (unless Gilbert's syndrome).No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
10. Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
11. No known allergy to mouse proteins or monoclonal antibodies

Exclusion Criteria:

1. Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The Protocol PI is the final arbiter of eligibility.
2. Pleural/pericardial effusion or ascites estimated to be >1L.
3. HIV-positive.
4. Pregnancy: Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
5. Known allergy to mouse proteins.
6. Patient has received other systemic chemotherapeutic drugs (including Mylotarg) within 21 days prior to trial enrollment. (Hydroxyurea or low dose ara-c < 20 mg/m2/d is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed LMD, that has been in remission for at least 3 months prior to enrollment on this study).