Trial Information

Phase I/II Study of Allogeneic Hematopoietic Stem Cell Transplantation From an HLA-partially Matched Family Donor After TCR Alfa Beta Negative Selection in Pediatric Patients Affected by Hematological Disorders

In this study the hypothesis is that the transplantation of Peripheral blood stem cells
(PBSC)selectively depleted of TCR alfa beta T lymphocytes would offers some advantages over
the use of positively selected CD34+ stem cells because of the presence of other non-stem
ancillary cells (in particular Natural killer (NK) and alfa beta T cells) that might have
potential positive effects on the outcome of the transplant.

The clinical relevance of NK-cell alloreactivity has been demonstrated in adult patients
affected by Acute myeloid leukemia (AML) and given T-cell depleted HSCT from an
HLA-disparate relative where a subgroup of patients had a particularly low risk of leukemia
relapse. These patients belonged to the group transplanted from a donor having NK cells that
were alloreactive towards recipient targets i.e. the patient cells express HLA-class I
alleles that do not share the inhibiting allelic determinants recognized by Killer
immunoglobulin-like receptors (KIR) on donor NK cells. The emergence of this concept of
NK-cell alloreactivity has represented a sort of revolution in the field of Haplo-identical
hematopoietic stem cell translantation (haplo-HSCT), as the presence of alloreactive NK
cells has been shown to positively affect the outcome of transplantation in adults and to
display a Graft versus leukemia (GvL) effect that can compensate for the lack of T-specific
anti-tumor effect.

The purpose of this study is to evaluate the feasibility and safety of the selective
infusion of TCR alfa beta T cell depleted graft in pediatric patients affected by malignant
or non malignant hematological disorders and receiving an HSCT from a partially matched
family donor.

This study will provide new data on the feasibility and the safety of using a TCR alfa beta
T cell depleted graft instead of fully T cell depleted graft to improve the outcome of
patients receiving a haplo-HSCT for the treatment of hematological disorders.