Haematopoietic chimerism and donor lymphocyte infusion after allogeneic SCT in children with non-malignant disease: is there an option to improve outcome?

Allo–SCT is a well-established treatment modality for children with several acquired and inherited disease affecting the haematopoietic stem cell or their derivatives. Treatment failures after allo–SCT are mostly caused by graft rejection (GR). Increasing mixed chimerism (in-MC) represents a stage at the very beginning of graft rejection, where immunological intervention might be an effective prophylactic approach. To substantiate this, we monitored haematopoietic chimerism after allo–SCT of peripheral blood samples and performed pre–emptive immunotherapy by donor lymphocyte infusion (DLI) in patients with in-MC.

54 transplantations were performed in 51 children at the University Children's Hospital Tübingen. During the course of follow up 28/54 courses were complete chimeras (CC) and 27/28 remained in continuous complete remission (CCR). One patient suffering from ALD showed progressive disease. 2/54 failed engraftment and recovered autologous (AR). Both died of serious infection. 24/54 showed in-MC. 15/24 received additional immunotherapy by DLI and 1/24 received a late stem cell boost. 14/16 remained in CCR or partial remission and only 2/16 showed progressive disease or GR. Whereas patients with in-MC without DLI rejected their grafts (2/8) or showed progressive disease (1/8). Two of them received a second transplant and stay now as CC in CCR. 1/8 died of TRM and only 4/8 remained in CCR. Only one patient with SAA facing a clinical GR receiving therefore repetitive DLI developed a severe GVHD.

These data substantiate that DLI in children with non-malignant disease and in-MC can prevent GR or progressive disease with a moderate risk to induce severe GVHD.