[CIS-PAGID] EBV infection and

[Michael Albert]

Eli, since you asked for it:
One thing is obvious: transplant as soon as possible (from an EBV
positive donor) as said before.
The rest is personal opinion: I would treat with ganciclovir, add
alemtuzumab to the conditioning as it might even bring down EBV load,
but give it as distal as possible i.e. day-14 or even -21 in order not
to compromise the donor T-cells too much. This will also help in
controlling the HLH. I personally would give a reduced intensity
regimen such as Flu/Mel or maybe Flu/Bu8, because this sounds like a
sick patient to begin with. Maybe this would be a patient in whom to
measure alemtuzumab levels on day 0. Cryopreserve T-cells in any case
and then you might consider a T-cell addback in case there was still a
considerable alemtuzumab level before transplant. CSA and MMF as GVHD
prophylaxis and adjust that depending on EBV load and (later)
chimerism.
Best,
Michael

PD Dr. med. Michael Albert
Oberarzt
Abteilung für Pädiatrische Hämatologie/Onkologie
Leiter der Stammzelltransplantation
Dr. von Haunersches Kinderspital der LMU
Lindwurmstr.4
80337 München
Tel: 089 5160 2785
Fax: 089 5160 4719



Michael Albert, MD
Assistant Professor
Department of Pediatric Hematology/Oncology
Head SCT Program
Dr. von Haunersches Kinderspital der LMU
Lindwurmstr.4
80337 München
Germany
Tel: +49 89 5160 2811
Fax: +49 89 5160 4719


On Thu, Dec 22, 2011 at 3:12 PM, Elie Haddad <elie.haddad at umontreal.ca> wrote:

> Given the absent cytotoxicity and the absent degranulation, it is very

> likely that this patient has a "true" primitive HLH and you should find

> mutation in Munc13-4, Munc18-2 (XLP related genes should be excluded since

> she is a girl) Also, look for partial albinism with hair microscope

> analysis. Therefore, transplantation is absolutely required (even if you

> don't find mutation).

> Since you observe so many copies afer Rituximab and you don't find

> circulating B cells, then EBV in in T lymphocytes or NK cells.

> I do agree with Jeff Cohen for transplantation: the sooner the better. To

> reduce EBV load before BMT, I don't see other means than Ganciclovir.

> In patients with chronic EBV infection who have been transplanted, some have

> been described with good evolution without engraftment suggesting that the

> conditionning regimen has "destroyed" the infected T or NK cells.

> The tough question is about GvHD prophylaxis. since it is a MUD, one ould

> like to be strong against GvHD, but since you will like a rapid immune

> reconstitution to control EBV, one would like to be weak..... Therefore, one

> could say no ATG and no alemtuzumab, but it is also possible that ATG or

> Alemtuzumab will induce a deep decrease of EBV load....

> I would go with a "classic" BMT with Bu-Flu (myeloablative) and CsA-MTX, but

> as I said, a reduced CR with serotherapy for GvH prophylaxis could be also a

> good option.

> I would like to hear the opinion of other "transplanters" in this case.

> Elie Haddad

>

> Elie Haddad, MD, PhD,

> Professor of Pediatrics, University of Montreal,

> Head, Pediatric Immunology and Rheumatology Division,

> CHU Sainte-Justine, 3175 Cote Sainte-Catherine

> Montreal, QC, H3T 1C5, Canada

> Ph: 1 514 345 4713

> fax: 1 514 345 4897

> e-mail: elie.haddad at umontreal.ca

>

>

>

>

>

> Le 2011-12-22 à 03:05, Pere Soler Palacin a écrit :

>

>

>

> Dear colleagues, this patient is currently being treated in another centre,

> here in Barcelona. We would appreciate your opinion about this case.

>

>

>

> Girl, 23 months-old, diagnosed in June 2011 of FHLH (EBV-induced). Absent

> cytotoxicity, normal perforin expression, absent degranulation, pending

> results of genetic studies. No CNS involvment. Treated following HLH-2004

> protocol, with good response to induction treatment (8 weeks) followed by

> maintenance treatment. Has had 2 relapses related to intercurrent

> infections, again well controlled with HLH2004 treatment intensification.

> She is pending a MUD (10/10) which is planned in one month aproximately.

> Unfortunately, she is currently with an uncontrolled EBV infection (>80

> million copies/mm3 in plasma, ferritin 40000 ug/L), despite 5 doses of

> Rituximab (has <10 B cells/mm3), and treatment with acyclovir, followed by

> foscarnet,. There are no signs of active hemophagocytosis (6% of CD8+DR+

> cells), under full HLH-2004 treatment: DXM 10mg/m2 daily + VP16 twice weekly

> + cyclosporine.

>

> What would you suggest regarding EBV treatment before BMT?

>

> Thank you 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; 34660psp at comb.cat. Web: www.upiip.com.

>

>

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