Graft failure

Abstract

Graft failure is a very serious, life-threatening complication of hematopoietic stem cell transplantation (HSCT) that is fortunately rare. A patient is considered to have graft failure if the patient lacks hematopoietic cell engraftment after HSCT. Graft failure can occur in both the autologous and allogeneic HSCT settings. Graft failure can be classified as primary or secondary. Both primary and secondary graft failure are defined as an absolute neutrophil count (ANC) <500/mm2. However, they differ in that primary graft failure has no evidence of engraftment by Day 28 after bone marrow or peripheral blood hematopoietic stem cell transplantation and by Day 42 after umbilical cord blood transplantation, whereas secondary graft failure occurs after hematopoietic stem cell (HSC) engraftment had already been established. Graft failure is multifactorial which can be categorized as quantitative, qualitative, or immunologic. Graft rejection is a cause of graft failure and is immune mediated. Poor graft function may result after HSCT as well. An HSCT recipient is considered to have poor graft function if the recipient does not have adequate, sustained blood counts but has full or nearly full donor chimerism and often responds to a boost of CD34+ donor stem cells via infusion. Because graft failure is associated with significant morbidity and mortality, every effort needs to be made to minimize the risk of graft failure. If graft failure occurs, then donor lymphocyte infusion(s) (DLI) and use of a CD34+ donor stem cell boost followed by G-CSF mobilization are employed. If these measures fail, and the patient dose not reconstitute with autologous HSCs, then the patient needs to undergo a second HSCT. This chapter discusses the risk factors, etiologies, and strategies to minimize the risk and to treat graft failure.