Engraftment and chimerism

The goal of hematopoietic stem cell transplantation (HSCT) is sustained engraftment. Engraftment is defined as neutrophil and platelet recovery after a period of aplasia. In order to be considered engrafted, the patient post-HSCT needs to have an absolute neutrophil count (ANC) >500 mm² for the first 3 consecutive days. Platelet recovery occurs when the patient has sustained a platelet count >20,000 µL^-1 for 3 consecutive days without a platelet transfusion in the 7 preceding days. Typically, neutrophil engraftment occurs first with platelet engraftment occurring 1-3 weeks later, depending on the donor and hematopoietic stem cell (HSC) source. Other factors that influence engraftment include the use of growth factors during the peri-HSCT period, the bone marrow microenvironment of the recipient, the HSC dose, and donor graft manipulation. Often at the time of engraftment, patients will develop a “flu-like” syndrome with fevers, chills, worsening mucositis, peripheral edema, joint and muscle aches, and/or abdominal pain due to a cytokine storm driven by donor T cells. The degree of donor engraftment is measured by the percentage of donorderived blood cells in the HSCT recipient, termed donor chimerism. Multiple studies have shown that sustained donor chimerism of >90% to 95% is associated with an improved event-free survival (EFS) and overall survival (OS). More importantly, a decrease in donor chimerism over time can predict the relapse of the underlying disease for which the patient was transplanted. Decrease and/or elimination of immunosuppression and donor lymphocyte infusions (DLI) may be able to reverse decreasing chimerism. This chapter reviews the timing of engraftment and the factors which influence it. Graft failure and rejection are addressed in Chap. 11. Methods to measure donor chimerism and the implications of changing donor chimerism percentage are also addressed.