[PAGID] rituximab vs PID

[Rhoda Kagan]

yes, it could. The more worrisome aspect of this child's management is the
fungal infection and the etiology of the T cell dysfunction.
R Kagan




"Ashish Kumar" <kumar036 at umn.edu>@clinimmsoc.org on 08/16/2005 03:30:46 PM

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Subject:  RE: [PAGID] rituximab vs PID




Couldn't the autoimmune hemolytic anemia be because of the underlying
thalassemia and the repeated transfusions?

Ashish Kumar, M. D., Ph. D.
Assistant Professor
Pediatric Hematology/Oncology/Blood and Marrow Transplantation
University of Minnesota

-----Original Message-----
From: pagid-bounces at clinimmsoc.org [mailto:pagid-bounces at clinimmsoc.org]
On Behalf Of Conley, Mary-Ellen
Sent: Tuesday, August 16, 2005 2:17 PM
To: pagid at clinimmsoc.org
Subject: RE: [PAGID] rituximab vs PID

I think it is possible that the low T cell numbers pre-date the
rituximab and the fungal infections.  We have been caring for a 5 year
old little boy who presented with autoimmune hemolytic anemia at 6
months of age.  He relapsed several times in the first 18 months of life
and was referred to us.  He had had some ear infections but nothing
suggesting T cell deficiency, not even candida on his plump little
behind.  During his first hospitalization at 6 months of age, he had an
absolute lymphocyte count of 900 (before any therapy).  When we first
saw him, he had 19% CD3+ cells and his proliferation to mitogens was
less than 5% of control.  His serum immunoglobulins were borderline low
with poor antigen specific antibodies.

We have treated him with rituximab in an attempt to taper his steroids.
That has been pretty successful but he relapsed when he was off the
rituximab for a year.  Now we are giving him rituximab every 6 months,
prednisone 0.5 mg qod, IVIG and daily bactrim.  Infections have not been
an issue.  His brother is not a match or we might have transplanted
early on.  Now he does so well that it is difficult to think it is worth
the risk.

I would use time to tell you which direction to go.  I would keep your
patient on the anti-fungals for another year and then taper him.  I
would try to get the steroid down as far as you can by using the
rituximab to keep his autoimmune hemolytic anemia away.

Maybe these boys have a syndrome?
Mary Ellen






Mary Ellen Conley, MD
Department of Immunology
St. Jude Children's Research Hospital
332 N. Lauderdale
Memphis, TN 38105-2794
FAX  901-495-3977
TEL  901-495-2576


-----Original Message-----
From: pagid-bounces at clinimmsoc.org [mailto:pagid-bounces at clinimmsoc.org]
On Behalf Of routesj
Sent: Tuesday, August 16, 2005 9:37 AM
To: pagid
Subject: Re: [PAGID] rituximab vs PID

I also have not seen T cell dysfunction with rituxin. I believe the most
likely reason for the abnormalities in T cell function  (assuming the
mucor infection has been adequately treated) is the ongoing treatment
with prednisone. We have seen CD4 lymphopenia with very small daily
doses of prednisione (10 mg/day) in adults. It is also possible that
posaconazole may have effects on T cell function in vitro, although I
could not find anything in the literature directly addressing this.
Jack Routes

--
John M. Routes, M.D.
Associate Faculty Member
National Jewish Medical Research Center
Associate Professor of Medicine and Immunology University of Colorado
Health Sciences Center

Address: 1400 Jackson St.; Denver, CO 80206
Phone: 303-398-1291;  FAX: 303-398-1806;  email: routesj at njc.org



Thanks for your thoughts.
He does not have any significant adenopathy, so it seems like ALPS is
unlikely.
Regarding CGD, we did measure function with a fluorescent assay, so
although we could pursue further with gene testing, we don't have much
to suggest this a phagocyte disorder.
The T cell #s and function have remained low despite complete radiologic
and surgical assessment of the mucor.  He has been debrided and looked
at several times noting NO further disease, but we are reluctant to stop
anti-fungals given the ominous prognosis of this infection. Having said
this, can we still accept this degree of T cell dysfunction based on the
infection?





Kathleen E.Sullivan <sullivak at mail.med.upenn.edu>@clinimmsoc.org on
08/16/2005 08:16:18 AM

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I have seen results of T cell studies in lupus patients after multiple
courses  of rituximab and there was no effect on T cell numbers so I
would be reluctant to ascribe the effect to rituximab.  I have a few
ideas in terms of his process that perhaps you have already addressed.
He can't really have SCID and be 11 years old so I presume you are
asking whether he could  have such significant T cell dysfunction that
he warrants a transplant.  I would wager that some degree of T cell
dysfunction is as a consequence of his fungus and you will see some
modest improvement over time.  Hard to believe he was born with this
degree of compromise and has had only AHA until now.   I know you have
tested for CGD but the NBT is not sensitive for mild mutations and CGD
patients can have low T cell numbers and function that can worsen after
fungal infections.  CGD would tie a lot of the features together so it
might be worth retesting with a more sensitive fluorescent assay.  My
last thought is whether he has had much adenopathy and should be tested
for ALPS.   The caspase deficient forms can look a lot like CVID and
have some unusual infections and could go along with AHA.

On Aug 15, 2005, at 4:12 PM, Rhoda Kagan wrote:

> Any suggestions as to the  management or diagnosis of this child are
> welcome!
>
>
>  11 yo Asian boy  with invasive murcormycosis following a course of
> rituximab for refractory autoimmune hemolytic anemia.  Subsequent
> immune work up noted T cell lymphopenia and poor T cell function.  Is
> this a result of rituximab? If so, should we anticipate some
> improvement (it has now been a year since last dose!) or did he have
> an undiagnosed PID without any significant infections until last
> year?? Our questions are
> twofold: 1.
> must he continue on anti-fungal treatment indefinitely (our ID
> colleagues have suggested that he should); 2. should we consider BMT
> if he is SCID?
>
> History:
>      -Born to non-consanguineous parents
>      - Thal Major dx'd at  8 mos;  autoimmune hemolytic anemia
> diagnosed in
>      the first year of life
>      -transfusion-dependent with multiple transfusion reactions,
> including
>      severe hemolysis, (Anti-Lu a Ab positive), initially managed with
>      pre-treatment  solucortef
>      *2003, hemolysis worsened;transfusion requirement
>      increased?..Prednisone commenced 10-40 mg qd
>      *2004, rituximab  (total 3 doses). Last dose july 2004 & IVIG q 4
>      weeks
>
>      -Sept. 2004: Mucormycosis infection of maxillary, ethmoid, and
>      sphenoid sinuses as well as peri-orbital region, treated with:
>      local and systemic amphotericin,  posaconazole, local irrigation
> and regular debridement, hyperbaric O2 (38 courses),  and G-CSF
>
>      -Current management/disease status (presently radiographically
> disease
>      free)
>      Posaconazole,  Prednisone , Septra prophylaxis, transfusions as
> required
>
> Immunology Work up  (all investigations done post-rituximab and
> unchanged on repeat testing) HIV negative NBT, complement:  normal
>
> CBC: WBC 3.6  Hgb 63 Plt Nl  ANC 2.3 ALC 0.8
> CD3 0.487 CD19 0.639  CD4 0.070  CD8  0.320 NK 0.139 PHA SI 1.22 IgG
> 9.82 (on IVIG); IgM 2.10 IgA 2.26
>
>
> Rhoda Kagan, MD
> Montreal Children's Hospital
> rhoda.kagan at muhc.mcgill.ca
>
>
>
>
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Kathleen E. Sullivan MD PhD
Associate Professor of Pediatrics
The Children's Hospital of Philadelphia
(p) 215-590-1697
(f) 215-590-3044








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