Analysis of the differential effects of anti thymocyte globulin (ATG) on lymphocyte subsets in patients with severe aplastic anemia

Acquired severe aplastic anemia (SAA) is a rare, immune-mediated disease
(incidence 2-3/million/year) characterized by a pancytopenia and an aplastic
bone marrow. Immune suppressive treatment with Anti Thymocyte Globulin (ATG)
combined with cyclosporine can induce responses up to six months after
treatment. Although it was hypothesized that the working mechanism of ATG in
SAA is based on its direct lympholytic effect on T cells, the ATG with the
strongest anti T cell effect (Thymoglobulin) is less effective in SAA than the
less T cell suppressive ATG forms (Lymphoglobulin and ATGAM). In order to find
out whether direct effects of ATG on different subclasses of lymphocytes can
explain the working mechanism of ATG in patients with SAA, an in-depth analysis
will be done of circulating and bone marrow lymphocytes before, during and
after treatment with ATG and levels and binding capacity of circulating ATG
derived antibodies will be measured in SAA patients receiving standard
treatment with ATG and cyclosporine.

* To evaluate the in-vivo effects of standard treatment of ATG and cyclosporine
on lymphocytes in patients with SAA.
* To evaluate persistence and binding capacity of circulating ATG derived
antibodies in patients with SAA after treatment.
* To compare these ATG effects on lymphocytes between SAA patients who do and
who do not respond to treatment with ATG

This is an observational study in which extra blood will be drawn for study
purposes. One extra bone marrow will be done at two months after start of the
treatment. The immunosuppressive treatment (IST) is regular care based on
national Dutch guidelines.

Extra blood will be taken during regular blood examinations (in total 270 ml
extra, divided over 6 time points in a 8 week period). One extra bone marrow
examination will be done (30 ml)