[CIS PIDD] [cis-pidd] ADA SCID tx

[Notarangelo, Luigi]

Agree with Paul! Also, you may want to have lineage specific chimerism
data.

Gigi


Luigi D. Notarangelo
Professor of Pediatrics and Pathology, Harvard Medical School
Jeffrey Modell Chair of Pediatric Immunology Research
Division of Immunology, Children¹s Hospital Boston
Karp Research Building, Room 10217
1 Blackfan Circle
Boston, MA 02115

tel: +1-(617)-919-2277
FAX: +1-(617)-730-0709




On 7/13/14 8:58 AM, "Szabolcs, Paul" <paul.szabolcs at chp.edu> wrote:

>Elena
>
>The data is not that hopeless with these details. A second donor search
>can be initiated but this graft is not lost yet. I would follow now Q2
>weeks chimerism and holding ADA at least till next dataset is worthwhile
>indeed.
>Best, Paul 
> 
>On 7/12/14, 9:09 AM, "Sokolic, Robert (NIH/NHGRI) [E]"
><sokolicr at mail.nih.gov> wrote:
>
>>Elena-
>>  I agree with what the others have said in terms of withdrawal of
>>immunosuppression. Would then start PEG-ADA. Rather than going to haplo
>>or another cord, I would advise looking for a MUD, b/c the child should
>>be stable after a 3-4 months on PEG. This is assuming that a MUD is less
>>toxic than a haplo as done by your transplanters  You could try
>>withholding the PEG while immunosuppression is withdrawn to give an added
>>advantage to the donor cells.
>>Rob
>>
>>
>>
>>From: Perez, Elena [e.perez13 at med.miami.edu]
>>Sent: Friday, July 11, 2014 12:26 PM
>>To: CIS-PIDD
>>Subject: RE: [cis-pidd] ADA SCID tx
>>
>>Jack and Cary- I double checked, on stem cell processing lab sheet and
>>TNC/kg=1.69x10^8 is listed, so previous email was a typo taken from EMR
>>chart. Today chimerism is back: Unseparated 6.7%; T lymph 5.47%; B lymph
>>8.82%; grans 2.72%, 40d post tx. Also match was 6/6 (there was a mismatch
>>at C locus so BMT coordinator called it a "7/8").
>>Summary of chimerism:
>>        unsep   T       B       gran
>>20d     2.75    0       2.6     1.6
>>30d     5.77    insuff  insuff  3.56
>>40d     6.7     5.47    8.82    2.72
>>
>>Baby is stable, room air, feeding.
>>Looking into PEG-ADA; discussing with transplanters here the next
>>steps...
>>Appreciate all the comments/suggestions.
>>
>>Thanks again!
>>Elena
>>
>>Elena E. Perez, M.D.,Ph.D.
>>Associate Professor
>>Chief, Pediatric Allergy and Immunology
>>Jeffrey Modell Diagnostic and Research Center for Primary
>>Immunodeficiencies
>>Division of Immunology and Infectious Diseases
>>Batchelor Children's Research Institute, Suite 316
>>University of Miami Miller School of Medicine
>>1580 NW 10th Avenue
>>Miami, FL 33136
>>
>>Office: 305-243-4863
>>Nurse (Maria Rodriguez) 305-243-9514
>>FAX: 305-243-7409
>>Email: e.perez13 at med.miami.edu
>>
>>
>>The information contained in this transmission may contain privileged and
>>confidential information, including patient information protected by
>>federal and state privacy laws. It is intended only for use of the
>>person(s) named above. If you are not the intended recipient, please
>>contact the sender by reply email and destroy all copies of the original
>>message.
>>
>>-----Original Message-----
>>From: Bleesing, Jacob [mailto:Jack.Bleesing at cchmc.org]
>>Sent: Thursday, July 10, 2014 9:28 AM
>>To: CIS-PIDD
>>Subject: RE: [cis-pidd] ADA SCID tx
>>
>>Elena:
>>
>>Are you sure about the cell dose that you shared with us?
>>
>>Jack
>>
>>________________________________________
>>From: Perez, Elena [e.perez13 at med.miami.edu]
>>Sent: Thursday, July 10, 2014 9:10 AM
>>To: CIS-PIDD
>>Subject: RE: [cis-pidd] ADA SCID tx
>>
>>Thanks for all the comments so far. I will pass them along. He has been
>>off of cyclosporine for a couple of weeks and results of next chimerism
>>(whole blood and lineage specific) are due today. I believe that match
>>was 8/8 but will double check. Will keep you posted & thanks again.
>>Elena
>>
>>
>>-----Original Message-----
>>From: Szabolcs, Paul [mailto:paul.szabolcs at chp.edu]
>>Sent: Thursday, July 10, 2014 8:32 AM
>>To: CIS-PIDD
>>Subject: Re: [cis-pidd] ADA SCID tx
>>
>>Agree with Gigi that withdrawal of Imm Supp drugs is your last hope but
>>if the repeat chimerism is falling below 5% it is going to be hopeless.
>>I have never seen clinically significant GVHD in this setting ( n: 5-7)
>>but the chances are very poor that it will work being so close to UCBT.
>>If You were at 100days or beyond with 5% donor cells  you may have a bit
>>more likely graft survival but even that would be against the odds
>>
>>I doubt that ADA SCID could engraft with Bu doses <12
>>
>>Best wishes, Paul
>>
>>
>>Paul Szabolcs, M.D.
>>
>>Professor of Pediatrics and Immunology
>>University of Pittsburgh School of Medicine Chief, Division of Blood and
>>Marrow Transplantation and Cellular Therapies, Children's Hospital of
>>Pittsburgh of UPMC http://www.chp.edu/CHP/bmt
>>
>>One Children's Hospital Drive
>>4401 Penn Avenue, Rangos, Room 5125
>>Pittsburgh, PA 15224
>>Phone:  412-692-6225
>>Fax:  412 692-7816
>>LR page: 412 958-6985
>>E-mail:  paul.szabolcs at chp.edu
>>
>>
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>>
>>
>>
>>
>>
>>
>>
>>On 7/9/14, 10:04 PM, "Notarangelo, Luigi"
>><Luigi.Notarangelo at childrens.harvard.edu> wrote:
>>
>>>Dear Elena,
>>>
>>>I assume chimerism is on total blood, correct? What is T cell count now?
>>>Can you do lineage specific chimerism? What immunosuppression? (You may
>>>consider reducing it to favor donor cells, although risk of GvHD would
>>>still be there). I see no advantage in rushing toward haplo. Lastly,
>>>did you adjust Bu exposure?
>>>
>>>Gigi
>>>
>>>Sent from my iPad
>>>
>>>Luigi D. Notarangelo, MD
>>>Jeffrey Modell Chair of Pediatric Immunology Research Division of
>>>Immunology, Boston Children's Hospital Professor of Pediatrics and
>>>Pathology, Harvard Medical School Karp Research Building, Room 10217 1,
>>>Blackfan Circle Boston, MA 02115 USA
>>>
>>>Tel: 617-919-2277
>>>FAX: 617-730-0709
>>>
>>>> On Jul 9, 2014, at 9:55 PM, "Perez, Elena" <e.perez13 at med.miami.edu>
>>>>wrote:
>>>>
>>>> Dear "transplant-for-Primary Immunodeficiency" community:
>>>>
>>>> We have a 2mo boy with ADA deficiency picked up on NBS who received
>>>>an HLA matched umbilical cord transplant on DOL45 after being
>>>>conditioned with 50% dose reduced Busulphan, Fludarabine and ATG and
>>>>rituximab, which was well tolerated. Stem Cell Dose: 16.7 x 10e5 CD34
>>>>pos cells/kg;
>>>>1.69 x 10e7 TNC/kg.
>>>>
>>>> Early evaluation of peripheral cell genotype unfortunately revealed
>>>>mixed chimerism of 3% donor suggestive of primary graft failure. His
>>>>most recent chimerism revealed 5% donor, and the transplanters are
>>>>planning to send another one this week before deciding about
>>>>retransplant. Today is +41d post transplant.
>>>>
>>>> In anticipation of need for retransplant, I offered to post his case
>>>>on the list serve for feedback to our transplanters. They are
>>>>considering retransplant with umbilical cord blood but hesitant to
>>>>redose chemo vs maternal haplo but clinimacs cell purification IND is
>>>>not available here.
>>>>
>>>> He is infection free but has developed seizures that are controlled
>>>>on Keppra. He is maintained on IVIG and all the usual prophylaxis and
>>>>so far has remained free of detectable infections, except on
>>>>presentation required oxygen which has improved to room air.
>>>>
>>>> He is on medicaid with very limited family resources, which makes it
>>>>difficult to transfer care out of state.
>>>>
>>>> Feedback from transplanters in the group appreciated, and will share
>>>>with transplanters here.
>>>>
>>>> thank you,
>>>> Elena Perez
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