Birgitta Versluijs

12 1 Limitations of HCT Successful HCT is considered disease free survival, with donor engraftment providing adequate immunity to prevent infections, in the absence of (severe) GvHD. For malignant diseases, HCT is not only used to simply replace the leukemia-affected bone marrow, but it is currently regarded as the most common and effective form of im- munotherapy. The role of the graft-versus-leukemia (GVL) effect in allogeneic HCT has been well established in several conditions. Novel therapies using dendritic cell vaccina- tions, tumor-infiltrating lymphocytes, and chimeric antigen receptor (CAR)T cells are being evaluated as potential adjuvants to HCT, or even to replace HCT. The outcome and efficacy of HCT in malignancies is influenced by several factors, including (remission state of ) the underlying disorder, the degree of graft-versus-leukemia/tumor (GVL/T) effect, and the toxicities associated with the preparative chemotherapy regimens. 2 In contrast, in non-malignant diseases there is no benefit from the graft-versus-disease effect. Here the engrafted donor cells compensate for the disease-causing deficiencies by producing certain lacking enzymes, normal hemoglobin or blood/immune cells. In many of these diseases less toxic therapies like gene therapy, especially avoiding the risk of GVHD, are expected to be used in the near future. 3-7 Limitations of hematopoietic cell transplantation Graft failure, disease recurrence, direct toxicity from conditioning, infectious problems (because of low immunity) and GvHD (because of increased donor immunity) remain important obstacles influencing morbidity and mortality and quality of life in HCT re- cipients. 8 Risk factors for these complications include donor/host HLA-incompatibility, disease status, viral status, donor source, conditioning intensity, degree of immune reco- very and time from transplantation. Virtually every organ can be adversely affected in some way after HCT, the most im- portant being the gastrointestinal, renal, cardiac, endocrine/fertility, metabolic and pul- monary systems. 9,10 Appropriate supportive care during HCT is essential, but life-long monitoring of survivors of HCT is also needed. Many late effects may not manifest for years or even decades, and early detection might mitigate the long-term consequences of some late effects. 11