ASH 2024 | Reducing the intensity of conditioning chemotherapy to promote GvL and reduce GvHD

I think one of the most important risk factors of graft-versus-host disease, obviously there is age, there is the conditioning regimen, the conditioning intensity. And the conditioning intensity has been throughout the years found to be associated with a higher risk of graft-versus-host disease. And so the whole idea right now is to see if we can lessen the intensity of the chemotherapy from myeloablative to reduced intensity or even non-myeloablative but with the addition of targeted agents that can help control the disease and promote time for the graft-versus-leukemia to develop without increasing the risk because in some malignancies like ALL or Richter’s if you use very low-dose chemotherapy the cancer cells can overcome the graft-versus-leukemia or graft-versus-lymphoma generated by the donor cells because the donor cells’ activity in generating this anti-tumor activity is powerful but it’s slow in time so you want to put a lid on the disease with the conditioning to give time for the graft-versus-leukemia and graft-versus-lymphoma to develop. So I think lowering down the intensity of the conditioning, but with the addition of targeted therapy, I think this is one of the ways to promote graft-versus-leukemia or graft-versus-lymphoma without the risk of graft-versus-host disease.

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