Cell Therapy in Pediatric Stem Cell Transplantation

Presentation Description: Allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for some children with life threatening hematological disease, immune deficiencies and in-born errors of metabolism and has been a successful therapy in use since the 1960s. In children most HSCT’s performed are allogeneic. In these instances an HLA identical related transplant offers the best therapeutic options as survival rates are amongst the highest and transplantation related morbidity and mortality amongst the lowest. Statistically, based upon Mendelian inheritance genetics, the chance of two siblings being matched is 1 in 4, whereas in practice approximately 39% of children referred for SCT will be matched with an identical sibling donor graft. For those without a compatible family donor, an unrelated donor search will enlist, in most cases, a suitable donor within three to four months of the initiation of the search.

Worldwide, over 15 million unrelated volunteer donors are registered. This allows for many children with malignant and life threatening conditions the chance of suitable rescue therapy within an acceptable time frame. However for those children without an acceptable donor and with the certainty that (left untreated) death will ensue, alternative donors must be sought. Haplo-identical transplantation is a procedure whereby peripheral blood stem cells from a donor who is an HLA full haplotype mismatch with the patient are used, is a feasible alternative. However, haplo-identical transplants are inherently more difficult that fully matched donor transplantations, with a higher risk of transplantation-related complications (especially graft dysfunction), life-threatening infections during the long immune-compromised period and thus transplant related mortality.

Despite advances in prevention and post transplant immune suppressive strategies, acute graft versus host disease (aGvHD) remains a major cause of morbidity and mortality in children undergoing stem cell transplantation. Acute GvHD occurs when transplanted donor T lymphocytes recognize antigenic disparities between host and recipient. Inflammatory cytokine release has been implicated as the primary mediator of aGvHD and activation of T cells is one step in a complex process. Deregulated cytokine release by cells other than T cells leads to tissue damage associated with aGvHD. GvHD is a factor that compromises the overall success rate of allogeneic HSCT and remains a challenge, which in turn requires an understanding of the pathophysiology, clinical presentation and management of this complication.

Within the bone marrow stroma, multi-potent precursors capable of differentiation into a number of mesenchymal cell lineages have been identified. These cells, called mesenchymal stem cells (MSCs), have been identified and characterized in humans. The feasibility and safety of co-transplantation of MSCs in the setting of haplo-identical SCT and in the treatment of GvHD and the clinical results of enhanced engraftment in the haplo-identical setting and reduced aGvHD were presented.


R. Maarten Egeler, MD, PhD
University of Toronto, Toronto, ON
Section Head Stem Cell Transplantation
Hospital for Sick Children, Toronto, ON

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