Transplant physicians based the design of the conditioning regimen on the notion that maximum dose intensity was required to create space for engraftment of new donor stem cells. It was thought that high-dose regimens were necessary to ablate every last malignant and nonmalignant clone. The high dose chemoradiotherapy approach was problematic due to considerable toxicity . A reduction in dose intensity of the conditioning regimen would be desirable but could compromise engraftment and/or relapse rate. Scientist discovered that there is lower relapse rate in patients receiving allogeneic transplants especially those with GVHD , through an effect known as GVL effect. They also discovered that if the host is given enough immunosuppresssion and large doses of HLA-identical PBPC , donor cells can create their own space and engraft. This was the idea behind the nonmyeloablative conditioning regimen. It has been tried in different centers with grate success in both malignant and non-malignant diseases but experience with this type of therapy is still limited and need larger clinical trials.