This month’s editorial article looks at the use of hematopoietic stem cell transplantation (HSCT) as a treatment option for acute myeloid leukemia (AML). This article will look at the different stem cell sources used for HSCT, the patients selected for an HSCT, and the current major issues in the pre- and post-transplant setting.
Transplant strategies for AML
Today, the only curative approach to treat patients with AML is the administration of high-dose chemotherapy followed by allogeneic HSCT (allo-SCT). Although autologous HSCT (auto-SCT) may still be an option for certain patients with favorable or intermediate risk AML, its use has been debated due to the fact that AML is a blood and bone marrow malignancy, thus transplantation with the patient’s own cells runs the risk of giving back some of the patient’s leukemia cells. 1In contrast, during the process of allo-SCT, cells from a donor are infused. This provides an additional benefit, called the graft- versus-leukemia or tumor (GvL or GvT) effect, whereby the donor immune cells have the potential of recognising and eradicating remaining leukemia cells in the host, thus reducing the risk of relapse. 2
Various donors can be used for an allo-SCT, while the best stem cell source remains to be from a human leukocyte antigen (HLA)-matched sibling donor (MSD). However, in approximately 70% of the cases such donors are unavailable, leaving the next best option of an HLA-matched unrelated donor (MUD). 3For patients where MSD or MUD are unavailable, a partially HLA-matched related donor can be used. This is referred to as haploidentical transplant (HD) and is usually a 50% HLA-match. In the past, HD has been associated with a slow immune reconstitution and high mortality from infections. Today, the use of post-transplant management treatments, like post-transplant cyclophosphamide (PTCy), reduces mortality and has made HD a viable option for patients with AML. This was further discussed by Arnon Naglerin his interview 4with the AML Global Portal (AGP) during the 2019 European Society for Blood and Marrow Transplantation (EBMT) meeting( video below). Nevertheless, HD still leads to inferior outcomes when compared to MSD in patients with AML (read AGP article here). Other donor types include cells from umbilical cord (read AGP article here) or from HLA-mismatched unrelated donors (MMUD). 2The impact of donor type on the outcomes of allo-SCT has recently been explored in an article by the AGP here. The authors of the study concluded that the traditional hierarchy of donors (MSD, MUD, and then others) remains true in patients with AML and should be used as a treatment algorithm.