[CIS PIDD] [cis-pidd] CTLs

[Cowan, Mort]

Dear Pere and Mike,

I agree that GVHD should not be much of an issue, but I would worry about a severe inflammatory process in the CNS.  We've had no experience with encephalitis but I've heard of patients with pneumonitis significantly deteriorating after CTLs for CMV pneumonia and wonder about what might have in the CNS and we did see this with CMV retinitis post CTL.  Unfortunately, for this child, there may not be any other option if the goal is still to attempt a cure.  I assume that the CMV is resistant to ganciclovir, foscarnet and cidofovir? We've had some success with Leflunomide for CMV resistant to these other drugs, but I agree that without some T cell immunity to the CMV, the chances for this child are extremely low.

Mort

Morton J. Cowan, M.D.
Professor of Pediatrics
Chief, Allergy, Immunology, and Blood and Marrow Transplant Division
UCSF Children's Hospital, Room M659
505 Parnassus Ave
San Francisco, CA 94143-1278

Phone: 415-476-2188
FAX: 415-502-4867

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From: Keller, Michael [mailto:MKeller at childrensnational.org]
Sent: Tuesday, January 14, 2014 8:53 AM
To: CIS-PIDD
Subject: RE: [cis-pidd] CTLs

Dear Pere,

I work with Cath Bollard's laboratory, who have a tremendous amount of experience in CTL therapy.

What I can tell you is that very few patients  have been treated with CTL outside of HSCT.  With that said, the Baylor group have done so successfully.   As long as the CMV-CTL are cultured sufficiently to eliminate alloreactivity (we use cytotoxicity and Ifn-G ELIspot testing against matched PHA blasts for release criteria), GVHD prophylaxis should not be necessary.

To clarify, you are referred to ex vivo cultured, CMV-specific CTLs from the mother - not DLI?

What cell dose are you planning on using?

Of note, our group at Children's National is in the process of opening a phase I protocol to treat PIDD patients with refractory CMV, EBV, and/or Adeno with CTL therapy prior to HSCT.   We are awaiting our FDA approval and we are hopeful that it will be approved within the next 1-2 months.

Best regards,
Mike

-------------------------

Michael D. Keller MD

Division of Allergy / Immunology

Children's National Health System

111 Michigan Ave NW, Room 1W-314B

Washington, DC 20010

Clinic: 202.476.3016

Office: 202.476.5843

Fax: 202.476.2280

www.childrensnational.org



________________________________
From: Pere Soler Palacin [psoler at vhebron.net]
Sent: Tuesday, January 14, 2014 11:24 AM
To: CIS-PIDD
Subject: [cis-pidd] CTLs

Dear all, I need your comments on another tough case. We a have a 5 mo girl with T-B-NK- (no specific mutation found) SCID ready for SCT who has developed a CMV encephalitis unresponsive to antiviral therapy and high dose ICIG. We are planning to infuse CTLS against CMV form her mother.

Does anybody has experience with this cell therapy in non-transplanted patients? Would you consider GvHD prophylaxis in this case? Any other thought?



Thanks in advance.



Pere



Pere Soler Palacín, MD, PhD.
Pediatric Infectious Diseases and Immunodeficiencies Unit. Hospital Universitari Vall d'Hebron.
Assistant Professor. Universitat Autònoma de Barcelona.
Passeig de la Vall d'Hebron 119-129.
08035 Barcelona. Spain.
Tel: 0034934893140. Fax: 0034934893039.
E-mail: psoler at vhebron.net<mailto:psoler at vhebron.net>; 34660psp at comb.cat<mailto:34660psp at comb.cat>. Web: www.upiip.com<http://www.upiip.com/>.



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