Graft failure in allogeneic haemotopoietic stem cell transplantation for non-malignant disorders: Basics and perspectives

Graft failure is one of the major causes of morbidity mortality after allogeneic haematopoietic stem cell transplantation, in particular for non-malignant disorders. Risk factors include HLA disparity, the use of T cell-depleted transplants, low doses of transplanted haematopoietic stem cells, viral infections, drug toxicity, and alloimmunisation due to inappropriate blood transfusions prior to transplantation. In patients at high risk for graft failure preventative strategies may include in vivo depletion of functioning host T cells and intensification of the post-transplant immunosuppressive treatment. Novel methods, such as depletion of only subsets of T cells or gene therapeutic graft engineering, may also prove to be useful in the non-malignant setting. The development of early mixed chimerism predisposes to subsequent graft failure, whereas specifically late mixed chimerism tends to be stable. In order to detect mixed chimerism as early as possible, chimerism studies should be performed close-meshed, especially in newly transplanted patients. In patients developing mixed chimerism, analysis of the T cell chimerism may reveal additional information of importance when making the appropriate therapeutic decision. Therapeutic options include modification of the immunosuppressive treatment, haematopoietic growth factors, donor lymphocyte infusions, application of booster doses of donor haematopoietic stem cells and second transplantation.