Haploidentical transplantation as a platform for post-transplant immune therapy in childhood leukaemia


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Rupert Handgretinger1
1Children’s University Hospital, Tübingen, Germany

Abstract

Allogeneic haematopoietic stem cell transplantation (HSCT) from a matched sibling (MSD) or a matched unrelated donor (MUD)is for a number of patients with malignant diseasesthe only curative approach. Over the time, the pool of potential donors has been increased by the addition of umbilical cord blood (UCB) and haploidentical donors (HAD). A major advantage of haploidentical transplantation is rapid donor identification and the continuous availability of the donor also after transplantation for further post-transplant cellular therapy strategies to avoid or to treat relapse of the underlying leukaemia. In order to prevent GvHD, in vitro graft-manipulation procedures to deplete T-lymphocytes from the graft are available and include CD34+ positive selection, CD3/CD19 depletion or the more recently described TcRαβ/CD19 depletionmethod. In addition, there is a choice of donor selection according to the donor'skiller immunoglobuline-like receptor (KIR) phenotype and NK alloreactive status.

The success of haploidentical stem cell transplantation depends, besides the eradication of the underlying malignant disease by the preparative regimen to a large extent on the balance between the donor's effector cells against the recipient's tissues and theirfavourable reaction towards the malignant cells (graft-versus malignancy effect). Over the years, convincingevidence has accumulated that the transplanted donor innate immune system contributes to the eradication of residual malignant cells.

Therefore, cellular therapeutic strategies using donor-derived effector cells will play a more and more important role not only for the prevention or treatment of relapse of the underlying disease, but also for the prevention of severe and life-threatening side effects, such as therapy-refractory viral or fungal infections of for the prevention and/or treatment of GvHD.