Fig. 2

Potential outcomes of different conditioning regimens in regards to transplant success. Top row without conditioning, the bone marrow (BM) is not depleted. After transplant, the lack of space, immunosuppression and disease eradication mean the donor cells do not engraft, leading to graft rejection and transplant failure. Middle row using standard conditioning: the BM is depleted, but the toxicity of the regimen leads to tissue damage. Reduced intensity conditioning (RIC) causes incomplete BM depletion. After transplant, the graft cells have space to engraft; however, the tissue damage leads to the release of inflammatory cytokines, which can induce graft-versus-host disease (GvHD). The donor cells can also mount a graft-versus-leukaemia (GvL) response against residual malignant cells. Using RIC, there is a risk of disease relapse caused by the outgrowth of residual malignant cells. The toxicity of conditioning is associated with transplant-related mortality (TRM). Bottom row antibody-based conditioning can lead to effective and targeted clearance of the BM niche, eliminating HSCs and progenitor cells while sparing host tissue by specific targeting of expressed CD markers. This can cause minimal toxicity and therefore reduce GvHD and TRM. For example, antibodies such as alemtuzumab and vedolizumab have been shown to reduce GvHD incidence, while radio-labelled antibodies such as ibritumomab tiuxetan have shown favourable toxicity profiles vs traditional TBI. Many pre-clinical ADCs have reported extremely impressive levels of BM clearance and engraftment after HCT in mouse models, which would positively impact transplant success if translated to human studies. It should be noted that not all antibody-based therapies provide such benefits, such as early studies associating gemtuzumab ozogamicin with increased toxicity. After transplant, the donor cells can successfully engraft due to effective clearance of the niche. Furthermore, the donor cells eliminate residual malignant cells by the graft-versus-leukaemia (GvL) effect