[PAGID] Atypical CGD family

[Sergio Rosenzweig]

Hi Dewton,
Marco's patient looks elegible for HSCT, what is not that certain is if
his brother is the best donor. I know about at least 1 CGD patient with
gp91phox revertant mutations that presented similar to your patient's
brother. Sequencing of the respiratory burst Pos and Neg populations
would help. The European experience (Seger and Gennery) with MUD in CGD
is encouraging, especially in children with no active inflammatory or
fungal infections. Conditioning in Europe has been myeloablative and at
NIH myelosupressive. 
Sergio

Sergio D. Rosenzweig, MD, PhD
Chief, Infectious Diseases Susceptibility Unit
Laboratory of Host Defenses, NIAID, NIH
10 Center Dr., Bldg. 10, CRC 5W-3888
Bethesda, MD 20892-1456
Phone (301) 451 8971
Fax (301) 451 7901
Cell (240) 361 7617
Pager 102 10678
srosenzweig at niaid.nih.gov
 
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>>> <dmvascon at usp.br> 01/21/10 1:51 PM >>>


I am posting this case presented to me by a colleague (Dr. Jose Marcos  
Cunha) from the Federal University of Rio de Janeiro. The patient is a  
5 year old boy with a severe form of X-CGD, but there are some  
questions mainly on the BMT aspects.

All the best,

Dewton


?	6 m/o - hepatic abscesses (negative blood cultures; no abscess  
aspiration/drainage was performed). Tx: 4 weeks  
amoxicillin/clavulanate+ metronidazol + gentamicin plus 2 weeks  
amoxicillin/clavulanate
?	2 y/o ? Cervical lymphadenopathy ? Salmonella sp. ? cephalexin
14 days
?	3 y/o ? A new pet arrives: a turtle.
      Then: Persistent diarrhea/intermittent fever ? Salmonella sp.  
enteritis (stool culture +) ?  Tx: SMX/TMP
?	3y 6 m/o ? Severe pneumonia. Initial Tx: amoxicillin/clavulanate
+  
amphoB + anti-TB + steroids
     BAL: Paecilomyces sp. ?  started on voriconazole, anti-TB
discontinued
      DHR test: abnormal ? 5 % (NR: 80-100%) ? CGD diagnosis
      DHR tests: mother ? 80% (one peak, not suggestive of X-linked CGD)
		         brother ? 87% = normal (repeated 2x)
?	3 y 9 m/o -  Started on SMX/TMP + itraconazol (Beatriz  
Costa-Carvalho); 9 y/o healthy brother had also abnormal superoxide  
production (formal report missing)
?	CXR ? same images. Chronic cough/intermittent fever
?	Lung biopsy: granulomatous inflammation. No evidence for fungal
or  
mycobacterial disease. Started on steroids (prednisolone 1 mg/kg).  
Clinical improvement; CXR: same aspect
?	High grade fever/chills: Abscess at surgical scar; spontaneous  
drainage. Discharged w/o culture of pus and oral amoxicillin/sulbactam
?	4 y/o ? Fever/Cough: Pneumonia ? no microbial isolation in
BAL/blood  
cultures. Tx: Ciprofloxacin + (Bactrim + itraconazol)
?	4 y 3 m/o
?	 Steroid tapering. Bactrim + itraconazol
?	Parents refused to change to voriconazole and/or adding
interferon  
gamma therapy
?	HLA typing for possible HSCT
?	Brother ? 100 % compatible
?	4 y 4 m/o ? Small erythematous lesion on right gluteus (insect  
sting?). Ocasional (intermittent) pain in right, knee, right tibia and  
right umerus
?	4 y 4 m/o
?	 USG of gluteal lesion: small amount of pus: FNA ? Serratia  
marcescens (sensitive: cefepime, ceftazidime; gentamicin, Taz/Pip;  
aztreonam;)
?	Started on cefepime IV tid
?	MRI: compatible with osteomyelitis (right proximal tibia, right 

umerus) ? drainage: Serratia liquefascens (tibia); Pseudomonas  
aeruginosa + Klebsiella pneumoniae (umerus)
?	Cefepime (continuous infusion) + voriconazole IV + SMX/TMP
?	Steroid (tapering) ? now with 0.5 mg/kg/day (prednisolone)
?	Waiting gamma-interferon
?	Check for donoŕs molecular diagnosis?
     (normal DHR 2x; abnormal superoxide production 1x; no clinical
disease)
?	4 y 9 m/o
?	 USG of gluteal lesion: small amount of pus: FNA ? Serratia  
marcescens (sensitive: cefepime, ceftazidime; gentamicin, Taz/Pip;  
aztreonam;)
?	Started on cefepime IV tid
?	MRI: compatible with osteomyelitis (right proximal tibia, right 

umerus) ? drainage: Serratia liquefascens (tibia); Pseudomonas  
aeruginosa + Klebsiella pneumoniae (umerus)
?	Cefepime (continuous infusion) + voriconazole IV + SMX/TMP
?	Steroid (tapering) ? now with 0.5 mg/kg/day (prednisolone)
?	Waiting gamma-interferon
?	Check for donoŕs molecular diagnosis?
     (normal DHR 2x; abnormal superoxide production 1x; no clinical
disease)
?	4 y 6m/o ? Day-clinic regimen (Pre-BMT)
?	Started on ertapenem (IV bid) + ciprofloxacin (IV) + SMX/TMP (PO
 
bid) + Voriconazol (PO bid)
?	 Steroid (tapering) ? now with 0.5 mg/kg/day (prednisolone)
?	gamma-interferon 3x/week (SC)

?	Excellent response to IFN-gamma therapy (6 week-course, stopped 

Nov/2009) plus antibiotics  No evidence of osteomyelitis according to  
scintilography examinations (Dec/2009)
?	Lungs apper better on chest X-ray (Jan/2010)
?	Laboratory tests ? unremarkable results
?	Present medications: SMX/TMP,voriconazole,amoxycilin and  
prednisolone 0.5 mg/kg
?	Blood samples (patient?s and brother?s) were sent to new
phagocyte  
function tests in São Paulo (Fleury Institute), due to previous  
conflicting results (reports of abnormal superoxide production (one  
test) and normal DHR oxidation (two tests) ? two different labs)
?	Results of this recent DHR oxidation test have show two
neutrophil  
populations in the candidate donor?s blood (see flow profiles in the  
next slides)
?	Can the HLA-compatible brother be still considered a good donor
?
?	Can molecular diagnosis (gp91phox sequencing) help in this
decision ?
?	Conditioning Regimen: RIC versus myeloablative
?	Should we transplant him now or wait for a molecular diagnosis
before BMT ?