Quantitative and qualitative analysis of T cells infiltrating the skin of children suffering from graft-versus-host disease

Allogeneic hematopoietic stem-cell transplantation (HSCT) is an important
therapeutic option for patients with hematological malignancies as well as
several non-malignant bone-marrow diseases. Children transplanted with
hematopoietic stem cells can be transplanted with several kinds of stem cells;
stem cells can be harvested from related donors or matched unrelated donors,
from the bone marrow or peripheral blood, and umbilical cord blood donors.
One of the major complications influencing the outcome after HSCT is
Graft-versus-Host Disease (GvHD). In this disease, donor T cells recognise host
(patient) antigens and hereby evoke a pathological immune reactivity. This
reactivity mainly affects skin, liver and intestinal tissue. GvHD can occur so
severely that patients can die.
Until current it is unknown whether the underlying mechanisms of GvHD after
HSCT with the different possible stem-cell sources are the same. However, it is
known that there are differences in number and function of T cells in the
several donor preparates. Preliminary data observed in Leiden showed a
different amount of certain T cells (CD8+, i.e. cytotoxic T-lymfocytes) in
gender-mismatched patients (female donor, male patient) than in gender-matched
patients. However, these data were gathered in a small amount of patients
transplanted with bone marrow donors. There are currently no data available
about GvHD tissue after HSCT with an umbilical cord blood donor.
We hypothesize that after different settings of HSCT (with different donors)
other types and fenotypes of T cells are involved in GvHD. When this is the
case, GvHD profylaxis as well as treatment can potentially be adjusted and made
more suitable for different HSCT settings. Furthermore, such findings can
provide the basis for new guidelines for donorselection.

This project aims at investigating the differences between number and fenotype
of T cells involved in GvHD when comparing:
a) gendermatches: gender-mismatched (female donor, male patient) versus
gender-matched (other combinations);
b) stem-cell source: bone marrow versus peripheral blood stem cells versus
umbilical cord blood;
c) donor relation: related (family) versus unrelated donor.

Cross-sectional, observational cohort study with an invasive measurement.

For every biopsy there is a risk of bleeding and infection. Bleeding from the
skin can usually be stopped by simple compression on the wound. To the best of
our knowledge, the risk of infection after punch biopsy for children after HSCT
has never been described. In general the risk of infection after skin biopsies
is considerd relatively small. The punch biopsy wound will heal leaving a scar,
the color of this scar will fade gradually.
There will be no direct benefit for the participants. However, the research is
group-related and can therefore not be conducted on other patient populations.
Furthermore, the only indication we have for differences in pathogenesis after
different kinds of HSCT have been observed in pediatric patients. And as
above-mentioned, HSCT settings in adult and pediatric patients are not
completely comparable, therefore, we believe we cannot answer our research
question for pediatric patients in adult patients.