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

Thu Aug 7 12:53:12 EDT 2014

With apologies for cutting to the chase:

1] There is/are triggers for his HLH (FHL genotype very unlikely, although there could be mono-allelic "genetic predisposition"). Likely viral reactivation that is currently fueling the fire because of using HLH-2004 -  a common scenario. Trigger[s] must be identified and treated on an ongoing basis. Keep in mind this patient was already 6 years old and most likely had already experienced an array of inconvenient viral infections (CMV, HHV-6, EBV, etc. etc). You might be lucky that one or both of the siblings now matches his viral profile. 

2] You have both donors available and should pick the one, who's cord unit is winning the "allogeneic contest". Unless - see above - you are dealing with viral issues in virus-naïve siblings and/or permissive HLH genotypes in siblings. In that case, you are better off with an URD that matches viral profile. 

3] Other than perhaps the age of the patient, do not quite understand using a non-myeloablative protocol for WAS unless they were already planning to follow-up with harvested "boost" from the sib donor. What works for CGD.......................

4] Ex vivo assays from the patient to characterize NK-cell biology likely not possible (post-BMT, post-HLH2005, etc.) and will not help in deciding what to do. 

5] In 20 seconds or less: Reinstitute full HLH-2004 therapy, consider HLH-salvage therapy. Take care of infections/reactivations with every means available. Line-up a "new" donor (winning sib if you can, URD if you must - and stay away unrelated UCB source) and use traditional myeloablative conditioning.

Good luck!
Jack

-----Original Message-----
From: Anders Fasth [mailto:anders at fasth.com] 
Sent: Thursday, August 07, 2014 11:14 AM
To: CIS-PIDD
Subject: Re: [cis-pidd] Transplanted boy with WAS

Thanks Kate, excellent idea. We have of course  looked for mutations in the twin donors, but that is two heterozygous mutations plus normal NK, Tcytotox function. Also, in the patient we found no mutation, but I am not sure if they have looked specifically in the two donor populations.
Anders
Anders Fasth
Granliden 27
433 60 Sävedalen

On 7 aug 2014, at 13:00, Sullivan, Kathleen <sullivak at mail.med.upenn.edu> wrote:

> Any chance you selected for a somatic mutation in the sisters donor pool or that the sister has latent HLH?  That would make you more likely to re-transplant with a different donor.
> 
> Kate
> Kate Sullivan, MD PhD
> Wallace Chair of Pediatrics
> Professor of Pediatrics
> ARC 1216 Immunology CHOP
> 3615 Civic Center Blvd.
> Philadelphia, PA 19104
> (p) 215-590-1697
> (f) 267-426-0363
> 
> 
> On Aug 7, 2014, at 4:31 AM, Anders Fasth <anders at fasth.com> wrote:
> 
>> 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) Mobile +46-76-050 6117 
>> (work) +46-70-687 5970 (private) Fax +46-31-707 0694
>> 
>> =====================================================================
>> ========
>> 
>> CONFIDENTIALITY NOTICE: This E-mail message, including any attachments, is for the sole use of intended recipient(s)and may contain confidential and privileged information. Any unauthorized review, use, disclosure or distribution is prohibited. If you are not the intended recipient, please contact the sender by reply E-mail and destroy all copies of the original message and its attachments without reading or saving in any manner.
>> 
>> Thank you
>> 
>> 
>> 
>> 
>> ---
>> The CIS-PIDD listserv is supported by the Clinical Immunology Society 
>> The science & practice of human immunology
>> 
>> P: +1.414.224.8095
>> E: info at clinimmsoc.org
>> 
>> Not a member of CIS? Please visit www.clinimmsoc.org to join!
>> 
>> You are currently subscribed to cis-pidd as: sullivak at mail.med.upenn.edu.
>> To unsubscribe click here: 
>> http://lm.clinimmsoc.org/u?id=183824771.d123d252090ca5b0b32c510b919da
>> 279&n=T&l=cis-pidd&o=45302978 or send a blank email to 
>> leave-45302978-183824771.d123d252090ca5b0b32c510b919da279 at lists.clini
>> mmsoc.org
> 
> 
> ---
> The CIS-PIDD listserv is supported by the Clinical Immunology Society 
> The science & practice of human immunology
> 
> P: +1.414.224.8095
> E: info at clinimmsoc.org
> 
> Not a member of CIS? Please visit www.clinimmsoc.org to join!
> 
> You are currently subscribed to cis-pidd as: anders at fasth.com.
> To unsubscribe click here: 
> http://lm.clinimmsoc.org/u?id=206766617.5c95ba4c31dd85cf0e4af4316a74a3
> b9&n=T&l=cis-pidd&o=45303377 or send a blank email to 
> leave-45303377-206766617.5c95ba4c31dd85cf0e4af4316a74a3b9 at lists.clinim
> msoc.org

---
The CIS-PIDD listserv is supported by the Clinical Immunology Society The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org

Not a member of CIS? Please visit www.clinimmsoc.org to join!

You are currently subscribed to cis-pidd as: jack.bleesing at cchmc.org.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=183824396.60ab2025d9ab67496282f5c977f33e12&n=T&l=cis-pidd&o=45304303
or send a blank email to leave-45304303-183824396.60ab2025d9ab67496282f5c977f33e12 at lists.clinimmsoc.org

---
The CIS-PIDD listserv is supported by the Clinical Immunology Society
The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org

Not a member of CIS? Please visit www.clinimmsoc.org to join!

You are currently subscribed to cis-pidd as: pagid at list.clinimmsoc.org.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=183939985.3ea13d40a15475ac00ebbd9cd8a37d6d&n=T&l=cis-pidd&o=45304801
or send a blank email to leave-45304801-183939985.3ea13d40a15475ac00ebbd9cd8a37d6d at lists.clinimmsoc.org