Health related quality of life (HRQoL) in childhood survivors of refractory GvHD treated with mesenchymal stromal cell infusions - a multi-center study

Refractory GvHD and mesenchymal stromal cell treatment
Hematopoietic stem cell transplantation (HSCT) has been a successful therapy in
use since the 1960*s and a proven cure for patients suffering from
hematological disorders as well as immune deficiencies and metabolic disorders.
For many of these children stem cell transplantation is the only curative
option.
Despite advances in pre-transplant immune suppression and donor HLA typing
methods (and thus donor selection), acute (a) GvHD remains a significant cause
of transplant related mortality and morbidity following allogeneic HSCT.
The initial management of aGvHD comprises of steroid treatment. This may be
combined with CSA, or tacrolimus. The majority of centers utilize methyl
prednisolone at 2.0 mg/kg/day. Approximately 50% of patients will remit or
improve with this treatment but the remainder requires second-line treatment,
which to date remains unsatisfactory.
There is presently no consensus as to salvage treatment in steroid refractory
aGvHD. Acute GvHD is considered steroid refractory when there is no response
to methyl prednisolone at 2.0 mg/kg/day for one week, or when there is
progressive disease at 72 hours with this dose.
Numerous agents have been reported as second line treatment and continue to be
evaluated. Whatever there initial effects, they have not fulfilled their
expectations and have had little impact on overall survival, which remains
dismal.
Recently, the infusion of third party MSC's has been described which
effectively eradicated steroid refractory GvHD that had failed all other
attempts at treatment. The hypothesis of action is that MSC's demonstrate
powerful immune-modulatory functions that can effectively down-regulate T cells
and thus diminish or eradicate GvHD.
A multi center treatment of steroid refractory GvHD with MSC infusions has
recently been reported with response rates of 70% and overall survival in
children in the region of 40%.

We propose to investigate the health related quality of life (HRQoL) in
childhood survivors of refractory GvHD who have been treated with mesenchymal
stem cell transfusions. This will be a multi center study involving the
Division of Clinical Immunology and Centre for Allogeneic Stem Cell
Transplantation, Karolinska Institute, Huddinge University, Stockholm, Sweden,
the Department of Pediatric Hematology Oncology, Fondazione IRCCS Policlinico
S. Matteo, University of Pavia, Italy, the Department of Paediatric Haematology
and Oncology, IRCSS Giannina Gaslini, Genova, Italy and Department of Pediatric
Stem Cell Transplantation, Leiden University Medical Centre, Leiden, the
Netherlands. Participating centers have agreed to collaborate once ethical
committee approval has been obtained by the organizing center, i.e. LUMC.

I Prospective, repeated measurements.
II. Retrospective.

not applicable