The proposed research focuses on the development of innovative protocol of mismatched stem cell transplantation with combined 2 different haplo stem cell transplantation (SCT) donors which are mismatched to the recipient (and preferably to each other), in a patient in need for SCT, lacking an HLA match related or an unrelated donor. This innovative protocol named multi donor stem cell transplantation (MDT) is designed to facilitate engraftment even when reduced intensity conditioning or a low cell dose are used, improve the graft vs. leukemia (GVL) effect and enhance immune reconstitution (using quantitative and qualitative parameters).

Inclusion criteria:

1. Patient age 0-70 years old with leukemia in 1st remission at high risk of relapse because of unfavorable prognostic features, at 2nd CR or MDS without an readily available matched donor (related or unrelated).
2. Patients must have a mismatched donor willing and capable of donating peripheral blood stem cells and/or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated (mismatched defined as 3/6-4/6 HLA matching).
3. Each patient / patient's guardian must sign written informed consent.
4. Patients must have an ECOG PS ≤ 2; Creatinine <2.0 mg/dl; Ejection fraction >40%; DLCO >50% of predicted; Serum bilirubin <3 gm/dl; elevated GPT or GOT <3 x normal values.

Exclusion criteria:

1. Not fulfilling any of the inclusion criteria.
2. Not in CR (if the indication for transplant is leukemia).
3. Active life-threatening infection.
4. Overt untreated infection.
5. HIV seropositivity, Hepatitis B or C antigen positivity with evidence of active hepatitis.
6. Pregnant or lactating women.
7. Donor contraindication (HIV seropositive confirmed by Western Blot, Hepatitis B antigenemia, HCV, evidence of bone marrow disease, unable to donate bone marrow or peripheral blood due to concurrent medical condition).
8. Previous autologous or allogeneic stem cell transplantation.
9. Inability to comply with study requirements.