Alexander's "Chimerism and tolerance in a recipient of a deceased-donor liver transplant" 2008

From wikipedia: "Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack."

[edit] Summary

A 9 year old girl got a liver from a dead donor.
She suffered severe hemolysis as a result of chimerism of blod cells.
As immunosuppressants were withdrawn, hemolysis arrested.
17 months after the transplant, she remains chimeric and has no signs of graft-versus-host disease.

"The change in this patient from group O, RhD-negative blood to group O, RhD-positive blood suggested the development of chimerism by engraftment of the recipient marrow from passenger hematopoietic stem cells within the transplanted liver."
"results suggested that the hemolysis was due to the production of antibodies by residual B lymphocytes in the recipient against engrafted erythroid cells from the donor."
"A choice between two therapeutic options was then considered: the use of rituximab, an anti-CD20 monoclonal antibody, which would deplete all B cells (both host and donor cells), or withdrawal of all immunosuppressive therapy to allow full engraftment. The decision was made to withdraw the immunosuppressive therapy."
- This resulted in hemoglobin levels remaining normal, reticulocyte levels returning to normal and a weak positive on antiglobulin tests for 28 months following.
Now they've done studies and she is definitely her donor's type in blood antigens. Furthermore, she required vaccination against measles and mumps; she had been previously vaccinated but her donor had not.

Bone marrow transplants (in which you sometimes but not always completely destroy the recipient's HSCs) often shows microchimerism.
Microchimerism has not shown clear evidence for aiding or discouraging tolerance of whole-organ transplants.
Because studies post-transplant show that the patient's HSCs were of donor type, hemolytic anemia seems to be because of the patient's remaining B cells. However, the fact that revaccination with common vaccines worked indicates that the present B cell population was of donor origin (which was naive to the vaccinations).
"This patient’s course is also consistent with animal models of mixed chimerism in which engrafting donor cells move through the thymus and host-reactive cells are deleted."
The authors point out many complications in the consideration of why this patient may have adopted the HSCs of the donor:
- the profound lymphopenia pre-transplant,
- the immunosupressive effects of post-transplant drugs,
- the infection of CMV (a virus) that could affect the immune system responsiveness,
- and the young age of the donor (12) and thus the potential for large numbers of stem cells transplanted.

The patient had hepatitis that required a transplant.
She got the transplant from a mismatched donor of the opposite gender.
She developed hemolytic anemia as a result of graft-versus-host disease.
Once they removed the immunosuppressant drugs, the hemolytic anemia went away and her hematological chimerism worked out.
"The complete absence of graft-versus-host disease and normal liver function in a fully HLA-mismatched, sex-mismatched liver allograft show that mixed chimerism with full tolerance can occur naturally under specific circumstances."