[CIS-PAGID] Rituximab and Chronic ITP

[Nelson, Robert P Jr]

Rafael,

One of the problems you may have considered is that of PML that has been reported in adults (mostly) post rituximab and some other monoclonals.  The largest series that I know of is below.   

	"Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project."
 	 Carson KR et al. Blood. 2009 May 14;113(20):4834-40.

The interpretation of the lymphocyte numbers in your patient to me is difficult with concurrent systemic infection.  Also if the boy was receiving steroids for the ITP at the time of IgG determination, then 478 is in a gray area and to me, the odds are higher for a rituximab consequence.  Although the ITP could be the first clinical evidence for CVID, I think it would be unusual to have encephalitis as a consequence new CVID after IVIG was initiated, especially without at least some history of previous infections.  Regarding your question (2) below, depends on what happens with this clinical problem, but I would want to re-do the work-up off IVIG if feasible.

Bob

Robert P. Nelson Jr., MD
Professor of Medicine and Pediatrics
Divisions of Hematology/Oncology
535 Barnhill Dr. Ste 473
Indianapolis, IN  46202
Telephone: 317-948-1186
E-mail: ronelson at iupui.edu
pager:  317-312-1773

-----Original Message-----
From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Rafael Firszt
Sent: Tuesday, December 06, 2011 3:26 PM
To: pagid at list.clinimmsoc.org
Subject: [CIS-PAGID] Rituximab and Chronic ITP

I am seeing a 14 yo boy with a history of chronic ITP and neutropenia who got Rituximab in March of this year.  He was just admitted to hospital with encephalitis of unknown cause. Before Rituximab was given he had an IgG of 478.  Since being admitted he got a dose of IVIG but no functional studies have ever been done on him.  He has no history of other infections.  

His Enumeration drawn last week shows:
CD4:CD8 Ratio:   ratio  * 1.05  
% CD19:  %  * 12  
% Natural Killer Cells:    * 3 L  
% CD3:  * 84  
% CD2:  %   86  
Absolute CD4   * 373 L  
CD4+CD45RO+ cells   * 249  
Absolute CD45RA   * 112 L  
Absolute CD8   * 356  
Absolute CD19   * 105  
Absolute Natural Killer Cells   * 30 L  
Absolute CD3  * 747  

Therefore he has low NK cells, low CD4 and low CD45RA.  It is interesting that his B cell count is normal.

He has ongoing work-up for his encephalitis but ID feels it is most likely virally-induced. 

I can't test him for function because of recent IVIG.

With history of ITP, neutropenia, initial low IgG and now encephalitis he likely has a form of CVID (I think). 
Based on this history I several questions:

1) Any other investigations?  (I have mitogen studies pending)
2) Would you continue IVIG monthly assuming he has CVID or would you stop and re-evaluate his function after several months to confirm the possible CVID
3) In CVID or after rituximab, have any of you seen low NK cells and low CD4 and low CD45RA in either of these situations?

Thanks for any help

Rafael Firszt
University of Utah