[CIS PIDD] [cis-pidd] Transplanted boy with WAS

[Elie Haddad]

Dear Anders,
indeed the case is weird...
If one considers primary HLH, then it would mean that the donor has primary HLH (weird...) and therefore, looking at NK cell degranulation in donors and in the patient would be necessary. Nevertheless, there is something that seems to me not logical with the hypothesis of primary HLH of the donor. Indeed, you said that you have a split chimerism, 1/3 male, 2/3 female. If the female has primary HLH, then 1/3 from a normal bone marrow should be enough  to control the HLH from the female, unless both donors have HLH...very weird...but why not, and this is the reason why I think you should test NK cell degranulation in both donors. Of course, if both donors have HLH, then you should retransplant with an unrelated donor. Really, when you think that these parents did HLA-PGD to cure their child with a WAS, and then both siblings have an HLH without any clinical signs but they transmitted HLH to their brother .....what a terrible story ...
Now, if one considers secondary HLH, then you have to rule out malignancy, autoimmunty and infection and I suppose you already did this. Nevertheless, sometimes it is not easy to rule out completely. However, there is one cause of secondary HLH that is rare and that can come with a kind of skin eruption that is Histiocytosis X. I remember a case I was involved in when I used to work in Alain Fischer's group. The patient had relapsig HLH-like episodes and skin eruption that eventually was histiocytosis X. Did your pathologist perform CD1a staining ?
I hope it helps...
All the best
Elie


Elie Haddad MD, PhD,
Professeur Titulaire, Département de Pédiatrie, Université de Montréal,
Chef du Service d'Immunologie, Rhumatologie et Allergologie Pédiatriques
CHU Sainte-Justine,
3175 Chemin de la Cote Sainte-Catherine
Montreal, QC, H3T 1C5, Canada
T: 514 345 4713
Fax: 514 345 4897
e-mail: elie.haddad at umontreal.ca

Le 2014-08-07 à 04:31, Anders Fasth a écrit :

> Dear All,
> This case below I have asked for advice earlier in July, but nobody replied. Too difficult case ???
> 
> I am still anxious for your advice. The update is even more troublesome: He was started on the HLH04 protocol again and after dexamethasone and two etopside his ferritin has gone from 2000 to 18 000. The pediatric oncologist are afraid of retransplantation, but does he has a chance without a new transplantation?.
> 
> The case as from my mail in late July.
> 
> I need your advice re a six year old boy with WAS transplanted with a double cord 14 months ago. Donors were his sibling twins (sister - non-carrier and brother) born after HLA-PGD. More or less eventful course for the first 3 months. Trombocytes returned to normal, full donors chimera, today about ⅔ female donor and ⅓ male donor. In late September last year he developed a rash that nobody could put a dx to: biopsy - no GvhD, possible eczema. In December, 8 months post SCT, he develops HLH with all typical findings and ferritin >100 000. New skin biopsy at time of HLH showed massive infiltrates of histeocytes. Nu mutation in FHL genes. Treated according to HLH-04 protocol and quickly clinically  better, but only slowly normalizing his ferritin over many months. 
> Now for about a month normal ferritin, but as steroids was tapered down his skin rash is back since a couple of weeks. And last week ferritin was slowly raising and is today 1900 + fever = relapse of his HLH.
> 
> My concern is of course  - how to get a sustained response. Should we re-transplant him? He has his matched twin siblings that now are 1 ½ years of age so we can use bone marrow this time. 
> 
> Anders
> 
> 
> Anders Fasth, MD, PhD
> Professor of Pediatric Immunology, 
> Dept of Pediatrics, University of Gothenburg
> Address: The Queen Silvia Children’s Hospital,
> SE-416 85 Göteborg, Sweden
> Tel +46-31-343 5220 (343 4000 switchboard)
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