[CIS-PAGID] post transplant BK infection

[Fleisher, Thomas (NIH/CC/DLM) [E]]

Interesting question, to my mind I would not use a heterozygous donor as the patient has proven to be susceptible to ALPS that the mother and evidently the brother are not (ie do not have the genetic and/or other factors/features that produce clinical disease). Since the other unknown factors necessary for disease are present in the patient - it seems like a real risk that clinical issues will recur if one gives a new marrow with the same genetic defect. Hopefully the brother does not carry the mutation, otherwise I would look elsewhere for the donor. 

Thomas A. Fleisher, M.D.
Chief, Department of Laboratory Medicine
NIH Clinical Center
301 496-5668 (T)
301 402-1612 (F)

-----Original Message-----
From: Nelson, Robert P Jr [mailto:ronelson at iupui.edu] 
Sent: Wednesday, June 29, 2011 7:48 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] post transplant BK infection

We are taking care of a 5 yr old with a novel 2 base pair deletion in FAS :  Allele 1: 851_852 del AG (V204fx209)predicted to affect an intracellular domain of the FAS gene and ALPS type Ia per the Cincinnati lab.  She has had a recent monoclonal B-cell proliferation and secondary HLH that has responded to therapy.  Mom and dad share a common haplotype and the mother and brother are full matches.  Our understanding of is that the rate of new mutations is unknown and that most ALPS Ia patients are found to have a parent with a heterozygous mutation. There are a small number of published reports regarding transplantation.  We are thinking about the approach, donor choice etc.  Questions:  If we find the gene in the asymptomatic mother and brother, would either be an acceptable donor.  To what extent would one evaluate the immunological function of the mother and brother. Is there experience other than that published with transplantation with alternative donors; successes or otherwise might be helpful. The family is supported by state Medicaid only and will probably have to stay in Indiana given their social situation.  Would share samples for further study if someone is interested.  Otherwise thoughts about the correction strategy would be appreciated.

Thanks,
Bob Nelson
________________________________________
From: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] on behalf of Aly.Mageed at helendevoschildrens.org [Aly.Mageed at helendevoschildrens.org]
Sent: Thursday, June 23, 2011 10:03 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] post transplant BK infection

I agree with Dr Nelson. I would also add that a low dose cidofovir has been helpful with lower renal and hematopoietic risks. We have used 0.5-1 mg/kg 2-3 times a week with hydration and without probenecid rather than the typical 5 mg/kg/week with probenecid with ? quicker resolution (hard to compare to historical control with so much variability between cases). We also check for adeno in addition to CMV.
In prolonged cases, other measures with cystoscopy and clot removal as well as prostaglandin  (carboprsot) irrigation or the use of estrogen are considered

Aly Mageed, MD
Division Chief, Pediatric Blood & Marrow Transplant
Helen DeVos Children's Hospital and Michigan State University
(616)-391-3962
aly.mageed at helendevoschildrens.org

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Nelson, Robert P Jr
Sent: Wednesday, June 22, 2011 5:33 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] post transplant BK infection

Richard,
Have seen about 15 cases post allo in adults.  Can be mild and transient or devastating-chronic, depending presumably on a number of factors:  donor source, conditioning intensity, ATG-containing conditioning/GVH prophylaxis, cyclophosphamide exposure, maybe severe GVHD and/or its treatment.  Its presence would indicate in my experience, perhaps hematological reconstitution but not immunological.   Treatment is dependent on donor source, disease for which the patient was transplanted, GVHD risk, because it may include reducing GVH-preventive therapy.  Anti-viral therapy not very potent in our experience, some try cidofavir, which carries with it significant renal toxicity.  We would be looking for CMV activation with weekly CMV PCR as a potential concommitant problem.  We anchor foley if hematuria is particulary bothersome or if clots.  We take foley out if it doesn't seem to be helping.  We try 3-way irrigation.  Anti-spasmodics may help a little.  Although it sometimes lasts for weeks or even monhts, not usually fatal.  Wide variation in BK DNA copy numbers from 10's of thousands to millions.  Initial value not especially informative but monitoring is somewhat useful I think.  Hope this helps and that the kid doesn't have a bad case of it.  Bob
________________________________________
From: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] on behalf of Richard Wasserman [drrichwasserman at gmail.com]
Sent: Wednesday, June 22, 2011 5:08 PM
To: PAGID
Subject: [CIS-PAGID] post transplant BK infection

My heme/onc colleagues have transplanted a two year old AML in remission who is now one month post-transplant and has reconstituted well. She would be home at this time but for severe hemorrhagic cystitis due to BK viral infection. Any suggestions?
Thank you,
Richard Wasserman

--
Richard L. Wasserman, MD, PhD
DallasAllergyImmunology
7777 Forest Lane, Suite B-332
Dallas, Texas 75230
Office (972) 566-7788
Fax (972) 566-8837
Cell (214) 697-7211