[CIS PIDD] [cis-pidd] Lung transplantation in CVID

Sat Mar 5 12:18:41 EST 2016

Richard and Bodo
I appreciate your comments and input

I have made the pitch about the lack of comorbidities etc..to the transplanters--- however, the pulmonologists are more concerned about the outcomes for their programs and will take no risks, real or imagined——I will reserve my comments on this topic to private conversations!

We did a WES and didn’t find anything (we have on other GLILD patients)—We have tried abatecept in one other patient who had no B cells in the periphery or lung  but LIP and granulomas—we did not have a  measurable response and he had a couple of invasive infections  so we stopped it and have not tried it on other patients to date.

In regard to the combination approach (BMT/Lung TX), that is an interesting idea. Looking back at his PFTs, we initially stopped immunosuppressive Rx (he got the usual courses of RTX/MMF) his FEV1/FVC was  (1.85/2.1~40% of predicted), we then noted a decline in lung function 8 months later (FEV1/FVC 1.65/1.9) so we restarted immunosuppressive Rx (MMF and rituximab when we saw B cells in the periphery), approximately 3 years later he is ~1.45/1.75. The average decline in FEV1 in non-smoking adult males  is ~30-40 cc/year so we have done a reasonably good job preserving his lung function but at some point in time will need a transplant. Will run this by our BMT group for their input and see if we can at least get an evaluation somewhere for lung transplant.

thanks again
Jack

John M. Routes, MD
Chief, Section of Allergy and Clinical Immunology
Professor of Pediatrics, Medicine, Microbiology and Molecular Genetics
Department of Pediatrics
Children's Hospital of Wisconsin
Medical College of Wisconsin
9000 W. Wisconsin Ave.
Milwaukee, WI  53226-4874
Phone: Office 414-266-6840
Fax: 414-266-6437
Email: jroutes at mcw.edu<mailto:jroutes at mcw.edu>

From: CLINICAL IMMUNOLOGY LISTSERV <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Reply-To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Date: Friday, March 4, 2016 at 3:55 AM
To: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Subject: Re: [cis-pidd] Lung transplantation in CVID

Dear Jack,

We had lung transplanted one female who later was diagnosed with CTLA4 deficiency.
She lived one more year with good QoL, but the lung disease returned and she died 12 mos post Tx despite a lot of IVIG replacement.
Do you know the genetics of your patient (CTLA4, LRBA, NFkappaB etc)?
But I agree there are a handful of other CVID cases being lung transplanted with not much success.
However, we have to consider that the 5yr survival of any lung transplant for any reason is only around 50%, depending on the center of course.

Have you tried abatacept in your patient ?

Have you considered to perform a BMT to treat the immune dysregualtion and therefore stabilise the lungs?
We did that in a patient from London an she is now 10 years post BMT and I have to confess that her lung still declines, but at a MUCH slower rate than with her initial immune system.
(she is the case in our series who actually was off IgG for some time as the new immune system started to produce some Ig but of not high quality, so she had infections and we put her bcd on IgG replacement).

How about a two-tiered approach?
First BMT and second LTX?

Hope this helps,
Best, Bodo

****************************************
Univ.-Prof. Dr. med. B. Grimbacher

Scientific-Director
CCI-Center for Chronic Immunodeficiency
UNIVERSITÄTSKLINIKUM FREIBURG
Tel.: 0761 270-77731  Fax: -77744
Breisacherstraße 115, 79106 Freiburg
bodo.grimbacher at uniklinik-freiburg.de<mailto:bodo.grimbacher at uniklinik-freiburg.de>
www.uniklinik-freiburg.de/cci

and

Consultant Immunologist
Institute of Immunity & Transplantation
Dept of Immunology
Royal Free Hospital
UNIVERSITY COLLEGE LONDON
Pond Street
London NW3 2QG
b.grimbacher at ucl.ac.uk<mailto:b.grimbacher at ucl.ac.uk>
www.centreforimmunodeficiency.com

Von: CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>>
Antworten an: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Datum: Wednesday 2 March 2016 15:57
An: CIS-PIDD <cis-pidd at lyris.dundee.net<mailto:cis-pidd at lyris.dundee.net>>
Betreff: Re: [cis-pidd] Lung transplantation in CVID

I encountered a similar problem about 25 years ago when I proposed a 35 yo XLA with severe hepatitis C (at the time nonA nonB) for liver transplant. I made the argument that IG replacement made him a better candidate because his infection risk would be decreased compared to other immunosuppressed transplant recipients who were not receiving IG. He was accepted, transplanted and lived more than 15 years post-transplant with an excellent quality of life for most of that time. If the patient does not have significant comorbidities other than GLILD, I think you could make a similar argument.
Richard Wasserman
Dallas

On Tue, Mar 1, 2016 at 11:43 AM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:
Dear All,
I have a 42yo male with CIVD that was diagnosed with "sarcoidosis" and treated with steroids for many years. When he came to our institution, the diagnosis of GLILD was made and we treated him with RTX/MMF (could not tolerate azathioprine). Unfortunately, he had moderate to severe pulmonary fibrosis with severe restrictive lung disease at the time of presentation and is O2 dependent. The immunosuppression has stabilized his lung disease, but with a normal decline in lung function with age he will require lung transplantation at some point in time. I have referred him for evaluation of lung transplantation, but so far two  programs have refused to even evaluate him citing CVID as a contraindication. There is a paucity of literature on this topic and most lung transplants I could find in the literature had other complications at the time of transplantation  (severe bronchiectasis, hematological abnormalities etc.,), which my patient does not have. He has been on immunosuppressive therapy for a number of years w/o serious infections and I believe that the pos-transplant immunosuppression (cyclosporin-MMF) would make a return of the GLILD highly unlikely. Does anyone have any direct experience in lung transplantation for pulmonary fibrosis due to GLILD in CVID.
thanks
Jack

John M. Routes, MD
Chief, Section of Allergy and Clinical Immunology
Professor of Pediatrics, Medicine, Microbiology and Molecular Genetics
Department of Pediatrics
Children's Hospital of Wisconsin
Medical College of Wisconsin
9000 W. Wisconsin Ave.
Milwaukee, WI  53226-4874
Phone: Office 414-266-6840<tel:414-266-6840>
Fax: 414-266-6437<tel:414-266-6437>
Email: jroutes at mcw.edu<mailto:jroutes at mcw.edu><mailto:jroutes at mcw.edu<mailto:jroutes at mcw.edu>>

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--
Richard L. Wasserman, MD, PhD
Allergy Partners of North Texas
7777 Forest Lane, Suite B-332
Dallas, Texas 75230
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Fax (972) 566-8837
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