Large numbers of patients now survive long term following hematopoietic stem cell transplantation (SCT), and late clinical effects of SCT are, thus, of major concern. Chronic graft versus host disease (cGVHD) and the associated immunodeficiency are the primary causes of transplant-related mortality late after allogeneic SCT and contribute directly or indirectly to most late complications. Despite the advent of new treatment modalities the incidence of cGVHD has remained high, related to several changes in clinical SCT practice (1) the expanded use of human leukocyte antigen (HLA) matched unrelated and HLA nonidentical related donors; (2) the increasing use of SCT in older patients; (3) the increasing use of viable donor lymphocyte infusions after SCT to treat relapsed disease or to achieve full donor chimerism after nonmyeloablative transplantation; (4) the increasing use of peripheral blood stem cells instead of bone marrow as a source of stem cells. In addition to cGVHD and its therapy, the major risk factor for late complications after SCT is the use of irradiation in the pretransplant conditioning regimen. The interrelationship between cGVHD, total-body irradiation (TBI), and nonmalignant late effects are summarized in Figures 29.1 and 29.2.

Secondary malignant diseases are of particular clinical concern as more patients survive the early phase after SCT and remain free of their original disease.

Nonmalignant late effects are heterogeneous, and although often non-life threatening, they significantly impair the quality of life of long-term survivors.