[CIS-PAGID] Transplantation for APECED ?

[Church, Joseph]

Elie:

 

Without an AIRE-producing thymus it doesn't seem that auto or allo
transplant has much of a chance.

 

To my knowledge the following has not been done, but may work: 

*	Campath suppression followed by fetal thymus transplant OR 
*	Simultaneous autologous transplant + fetal thymus OR
*	Simultaneous allogeneic transplant + fetal thymus.

 

JC

 

 

 

________________________________

From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Elie Haddad
Sent: Wednesday, July 13, 2011 9:04 AM
To: pagid at list.clinimmsoc.org
Subject: [CIS-PAGID] Transplantation for APECED ?

 

Dear all,

I follow a 22 years old girl with APECED (proven AIRE mutation) with
very severe autoimmunity.

The only treatment that was considered efficient was Rituximab for many
years (since 2005) and she was treated by one injection every 6 months.
I informed the patient about the risks of repeating Rituximab but she
said that her endocrinologic autoimmunity was very uncomfortable and the
only treatment that worked was Rituximab and she did not want to stop.

18 months ago, she presented with extensive pulmonary embolism related
with deep venous thrombosis (we did not understand why she did this)
that could be efficiently treated. During the hospitalization, we
noticed a very severe anemia that did not resolve and that was
eventually considered as autoimmune central anemia. Indeed, the anemia
was central, Epo was normal, there was no anti-Epo antibodies, and
marrow specimen showed plenty of T cells infiltrating the marrow and
surrounding reticulocytes (I could not see the slides, this is what said
the haematologist). To treat this autoimmune central anemia, we stopped
Rituximab and tried ATG + FK506 and then MMF in accordance with
haematologist advise. This treatment was unsuccessful and she is
presently transfused with red cells every 3 weeks with ferritin
dangerously growing up (even if somewhat stabilized by oral iron
chelation)...

We are therefore facing a very severe autoimmune central anemia that is
resistant to Rituximab (that has been restarted recently to control her
endocrinologic autoimmunity), MMF, anti-Calcineurine, ATG. She is under
sub-cu IG for immunoglobulin replacement because of repeated rituximab.
Given the T cell infiltrate in marrow (that is not a leukemic
infiltrate), we consider that we are facing a T cell autoimmunity and we
don't feel that plasmapheresis could work. 

The question is regarding bone marrow transplantation. I know it may be
a strange idea but our haematologist colleagues propose to perform an
allogenic HSCT. I would like to have your opinion. Given that AIRE
deficiency is a thymic disorder, allogenic HSCT should not work. The
only way it could work would be that thymus function in older patients
is not perfect and that the new immune system may not be miseducated.
However, if this theory works, then an autologous HSCT after < radical >
immunosuppression to "reset" the immune system should work also and
would be less dangerous than an allo-HSCT.

What do you think ? Allo ? Auto ? Has anyone already done an HSCT for
APECED ? HSCT (auto or allo) doesn't make any sense ? Other proposition
to treat this autoimmunity?

Thank you for your feedback.

Elie

 

PS: sorry for the long text (it's a complicated story), and sorry for
the possible English mistakes from a "French" Canadian.

 

 

Elie Haddad, MD, PhD;

Professor of Pediatrics, University of Montreal,

Head, Pediatric Immunology and Rheumatology Division,

CHU Sainte-Justine, 3175 Cote Sainte-Catherine

Montreal, QC, H3T 1C5, Canada

Ph: 1 514 345 4713

fax: 1 514 345 4897

e-mail: elie.haddad at umontreal.ca

 








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