Infezioni e Trapianto di CSE - academy-congressi.it · Infezioni e Trapianto di CSE Andrea...
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InfezionieTrapiantodiCSE
AndreaBacigalupoIstitutodiEmatologiaFondazionePoliclinicoGemelliUniversita’ CattolicadelSacroCuoreRoma
Varese18.maggio.2017
-5000
500100015002000250030003500
-7 0 30 100 200 365
cellu
le /m
mc
PMN CD4
Gv HD
condit
HSCT
HSV
CMV
EBV
CyA + MTX (or FK506 or MMF)
Tx of aGvHD (Pred + other)
B.Inf Fungal infections
enteropathy
1. Infections and GvHD
GvHD (clinical and subclinical) plays a major role in post-transplant infections
GvHD needs to be PREVENTED
1970 1980 1990 2000 2010 2017
MTX
ALG
1970 1980 1990 2000 2010 2017
MTX
Cyclosporin A
TCD ex vivo
ATG /CAMP
MTX
1970 1980 1990 2000 2010 2017
MTX
Cyclosporin A
CyA+MTX
TCD ex vivo
T CD in vivo (ATG /CAMP)
1970 1980 1990 2000 2010 2017
MTX
Cyclosporin A
CyA+MTX
TCD ex vivo
T CD in vivo (ATG /CAMP)
CyA + MMF
FK+ Sirolimus
1970 1980 1990 2000 2010 2017
MTX
Cyclosporin A
CyA+MTX
TCD ex vivo+
T CD in vivo (ATG /CAMP)
CyA + MMF
FK+ Sirolimus
PTCY
36
1611
6 5
05
10152025303540
GvHD III-IV
% o
f pat
ient
s
<80 80-90 90-2000 2000-2010 >2010
P<0.00001
Reduced incidence of severe GvHD
2. Infections and GvHD
Significant reduction of severe GvHD with time
CD4recovery after HSCTmedian counts
CsA+MTX+ATG
CsA+MTX+ATG
CsA+MTX
CsA+MMF+PTCY
3. Infections and GvHD
Immune reconstitution depends on GvHD prophylaxis, and donor
Incidence ? Severity ?
CI of infectionsI-II : non severeIII lethal (with or without other cause GvHD)
Predisposing factors?
Each pre-transplant bacterial infection/yearleads to an additional 2.15 post-HSCT bacterialinfection year (p=0.004)
Pre HSCT Post HSCTInf/year <2 2.3Inf/year >2 4.3 0.01
GvHD increases the incidence of infections
GvHD increases the severity of infections
HR of infectious deathfor GvHD+ vs GvHD-= 2.8
Bacterial infections and acute GVHD
Sayer, Blood 1994
4. Bacterial Infections and GvHD
Risk factors
Pre-Tx bacterial infectionsGvHD (increases the number and severity )
Impact of IFDs in the overall survival at 1-year from transplant 2008-2010
Parameter Pr > ChiSq HazardRatio
95%HazardRatioConfidence
LimitsIFD, time dependent <.0001 3.149 2.526 3.927aGVHD:0-1vs2-4 <.0001 1.432 1.211 1.694Stem cell source:BMvsPERIPH
0.3202 0.910 0.755 1.096
Stem cell source:CBvsPERIPH
0.0420 1.300 1.010 1.674
Donor:Matched relvsunrelated
0.0030 0.769 0.646 0.914
Donor: Mismatchedrel vsunrelated
0.0131 1.475 1.085 2.004
Age,continuous <.0001 1.014 1.008 1.019Disease phase attransplant:CRvsnoCR
<.0001 0.466 0.386 0.561
Disease: ALvsother <.0001 1.630 1.354 1.961
Multivariate analysisCommissione Infezioni
5. Fungal Infections and GvHD
# risk factors areGvHD, age, advanced disease, acute leukemia
# IFI increase mortality
If GvHD promotes infections andinfectiousmortality
Preventing severeGvHD should reduceinfectionrelatedmortality
60
36
221617
1116
695
0
10
20
30
40
50
60
70
Death I+G GvHD III-IV
% o
f pat
ient
s
<80 80-90 90-2000 2000-2010 >2010
P<0.00001
Reduced incidence of severe GvHDn=2455 allogeneic HSCT
6. Infections and GvHD
YES:
Prevention of GvHD decreasesmortality due to infections (+ GvHD)
Newtrends?
Bacterial infections andGVHD:themicrobiota
Manzo,Blood2015
Bacteriodes
Firmicutes
SCFA
Ep cells
TLR
LPS
Defensins
Treg Th 17
AgMcell
IgA
Peyer’s patch
Th 1 Th 17
IL-6
IL-10
TNF
Retinoic acid
Flagellin
IL-10
Bacterial infections andGVHD:themicrobiota
• Fecal analysis from94patients until day +35
Taur,CID2012
CONCLUSIONS
Very strong correlation of GvHD and infections
Effective prevention of GvHD is the secret for successful allogeneicHSCT
Genova BMT UnitE Angelucci AM Raiola,F Gualandi, A Dominietto,R Varaldo, M T Van Lint , S Bregante, C di GraziaT Lamparelli
Commissione InfezioniCorrado Girmenia
Gemelli BMT UnitS Sica, L Laurenti, P Chiusolo, F sora’, S Giammarco, E Metafuni, I Innocenti, F Autore
Nursing team Data ManagerR OnetoG Conti M Daneri
Genova ID UnitC ViscoliM MikulskaV del Bono