Haemopoietic stem cell transplantation for genetic disorders

Abstract

Stem cell transplantation (SCT) is used to cure or greatly ameliorate a wide variety of genetic diseases, ranging from inherent defects of haemopoietic cell production or function to metabolic diseases mostly affecting solid organs. It ranks as one of the most remarkable therapeutic advances of the past 40 years. Despite rapid technological improvements, however, there are still many short term risks and potential long term toxicities. As a consequence, the rapid emergence of alternative therapies (including new drugs, enzyme and gene therapies), necessitate constant re-evaluation of the risk/benefit ratio for each disease and hence the appropriateness of SCT. This review describes the major aspects of the transplant process, indications for transplantation, outcome statistics, and areas where alternative therapies are becoming available.

Figure 1

PCR amplified segments of microsatellite regions adjacent to genes allow distinction of donor and recipient DNA from marrow or peripheral blood cells. Here white blood cell and T-cell DNA have been analysed in a patient with Fanconi anaemia. After initial full donor engraftment, T-cells were mostly recipient in origin at 18 months post-graft—the probable cause of persistent lymphopenia in this patient.

Figure 2

Femoral remodelling after successful SCT for malignant infantile osteopetrosis. At presentation the bone is chalky white, lacks cortico-medullary differentiation, and has frayed metaphyses (mimicking rickets). By two years after SCT, bone density is almost normal and remodelling has occurred.