[PAGID] ?Unique XHIM patient

[Jack Bleesing]

I envision 3 circles that overlap, depending on the size of the circles. The size of the overlap is some indirect indication (cost/benefit ratio) of BMT. One circle represent the clinical phenotype of CD40L deficiency in this patient. If the mild mutation of CD40L translates into a mild clinical phenotype, I could be on Mary Ellen's side. The second circle would represent the donor situation. In the presence of HLA-matched sibling the circle would be big and the size of the overlap would be big[ger] as well. The third circle is the overall health of the patient. If neutropenia or other complications become troublesome or interfering with prognosis, quality of life, etc, the overlap would be of bigger size. In other conditions (e.g. ALPS) this circle can be the biggest, for example because [long-term] immunosuppressive therapy of autoimmune issues has caused significant problems, even if the first circle represents a "typical" [mild] phenotype and even if we have to use a matched unrelated donor (which is not such bad thing in an experienced transplant facility).
 
Moral of the story, drawing circles can be "therapeutic" in many ways!
J
 
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Jack J.H. Bleesing, M.D., Ph.D.
Associate Professor of Pediatrics
Cincinnati Children's Hospital Medical Center
Division of Bone Marrow Transplantation and Immune Deficiency
3333 Burnet Avenue, MLC 7015
Cincinnati, OH 45229
513-636-4266 (phone)
513-636-3549 (fax)



>>> "Conley, Mary Ellen" <maryellen.conley at STJUDE.ORG> 7/21/2010 2:32 PM >>>

Hi Joe,
I would guess that most of my colleagues will disagree with me but I would not push for transplant in this patient.  His mutation in CD40L would be considered a mild mutation - it is likely that it impairs but does not ablate correct splicing of the message.  His normal IgG and lack of infections also suggests milder disease.  I doubt the neutropenia is due to hematophagocytic syndrome.  There are old data indicating that stromal cells express CD40 and secrete G-CSF in response to CD40L.  However, only some patients with CD40L deficiency have neutropenia.  Maybe we can blame the modifying genetic factors?  Most of the push for transplant in patients with CD40L deficiency comes from the European review that showed that patients had a high incidence of crypto and sclerosing cholangitis and a high incidence of death in the 3rd decade.  The crypto does not seem to be as common in CD40L deficient patients in the US.
Mary Ellen





Mary Ellen Conley, MD
Department of Immunology/ Mail Stop 351
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
FAX  901-595-3977
TEL  901-595-2576


-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Kimberly Risma
Sent: Wednesday, July 21, 2010 9:55 AM
To: pagid at list.clinimmsoc.org 
Subject: Re: [PAGID] ?Unique XHIM patient. .

Does he have antibody titers to vaccines?
Have you tested more than one Ab for CD40L (including the CD40:FC reagent)?
Because sometimes one Ab will not recognize the epitope of the protein but another will. We can help you with this if need be, Kim

Kimberly Risma MD, PhD
Assistant Professor
Allergy Immunology
Childrens Hospital Medical Center
3333 Burnet Ave, mlc 2000
Cincinnati, OH 45229
Kimberly.Risma at cchmc.org 


>>> "Church, Joseph" <JChurch at chla.usc.edu> 7/20/2010 4:17 PM >>>

Colleagues:



I am seeing an 11yo boy with XHIM for a second opinion regarding management.



*       He has had no infections indicative of B-cell/antibody
deficiency.
*       He has had intermittently severe neutropenia since 2yo, now
requiring increasing doses of G-CSF.
*       His IgG and IgM levels prior to IVIG therapy were normal; IgA
was undetectable.
*       1% of activated CD3+CD4+ express CD154.
*       He has a novel mutation: 290(-7) T>G in the splicing receptor
site of intron 2.
*       A recent bone marrow showed "cellular marrow with trilineage
hematopoiesis; left shifted granulopoiesis."
*       Two sibs are not HLA matches.



Could the neutropenia be autoimmune?



Does hemophagocytic syndrome/macrophage activation syndrome cause unilinear (in this case granulocyte) cytopenia?



I think HSC transplant is still indicated.  Would anyone disagree?



Thank you for your help.



Joe Church

Childrens Hospital Los Angeles








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