Birgitta Versluijs

11 Introduction 1 is the limited amount of stem cells in the graft. In order to replace blood production in the marrow by donor-derived hematopoiesis se- veral hurdles need to be overcome: elimination of the recipients’ hematopoietic stem cells and immune system are essential. This part of the treatment is called conditioning. Conditioning regimens are based on chemotherapy or Total Body Irradiation (TBI). In myeloablative regimens, total ablation of the bone marrow cell compartment is the goal, giving the donor stem cells direct opportunity for engraftment. In non-myeloabla- tive regimens, also called reduced intensity conditioning (RIC), less intensive preparative treatment is used, not eliminating the whole hematopoietic system of the recipient, but relying more on slower donor cell influx after HCT. Serotherapy (such as ATG, campath) is another important component of conditioning regimen, given to prevent graft rejection and GvHD in case of an unrelated donor. The main mechanism of action is in vivo depletion of (T) lymphocytes. After the conditioning treatment, donor stem cells are infused. There will be a period of aplasia until donor engraftment takes place, usually leading to recovery from neutrope- nia in 2-4 weeks, and recovery of full immunity in the months to follow. In almost all pa- tients, immune suppressive (IS) therapy is given to prevent GvHD. Eventually tolerance will occur between donor immunity and host, diminishing the chance of GvHD, so IS can be tapered (Figure 1). FIGURE 1. Schematic overview of hematopoietic cell transplantation (HCT). Graft versus Host Disease (GvHD) Direct toxicity conditioning Infectious threat

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