[CIS-PAGID] Transplantation for APECED ?

[Elie Haddad]

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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