Hey #hematology aspirants, let's talk about #CMV today !! Post allogenic transplant CMV prophylaxis and pre-emptive therapy to be precise.
A short thread 🧵
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#MedTwitter #MedEd #hematology
A short thread 🧵
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#MedTwitter #MedEd #hematology
CMV a DNA virus, one of the commonest causes of infections post HSCT
Has the largest genome of any known human virus [200 genes]
Most humans harbour latent CMV, infection aquired in childhood.
Site of latency in humans-❓
In murine models- hepatic sinusoidal cells.
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Has the largest genome of any known human virus [200 genes]
Most humans harbour latent CMV, infection aquired in childhood.
Site of latency in humans-❓
In murine models- hepatic sinusoidal cells.
2/n
The risk of reactivation depends on CMV sero status:
D-/R+ > D+/R+ > D+/ R- > D- / R -
Other risk factors are:
1️⃣T cell depletion
2️⃣HaploSCT
3️⃣UCB SCT
4️⃣GVHD requiring steroids
So why not give prophylaxis to these "high-risk" patients ??
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D-/R+ > D+/R+ > D+/ R- > D- / R -
Other risk factors are:
1️⃣T cell depletion
2️⃣HaploSCT
3️⃣UCB SCT
4️⃣GVHD requiring steroids
So why not give prophylaxis to these "high-risk" patients ??
3/n
Most antivirals are #toxic !!
Either myelotoxic or nephrotoxic !! Can't afford either. (Things are changing now with #Letermovir)
The solution ➡️➡️ Pre-emptive Rx.
So we monitor viral load and treat above a certain threshold.
But what threshold ?
And how do we monitor ?
4/n
Either myelotoxic or nephrotoxic !! Can't afford either. (Things are changing now with #Letermovir)
The solution ➡️➡️ Pre-emptive Rx.
So we monitor viral load and treat above a certain threshold.
But what threshold ?
And how do we monitor ?
4/n
No set guideline. The threshold depends on the patient serostatus and other risk factors
Lack of standardized reporting further compounds the issue
We monitor using qPCR at weekly intervals till D+100, longer if active GVHD
>500copies/ml➡️start pre-emptive Rx
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Lack of standardized reporting further compounds the issue
We monitor using qPCR at weekly intervals till D+100, longer if active GVHD
>500copies/ml➡️start pre-emptive Rx
5/n
1st line pre-emptive Rx➡️➡️ Ganciclovir (5mg/kg BD)
Other FDA approved options:
1️⃣Foscarnet(90mg/kg)
2️⃣Cidofovir(5mg/kg/wk)
3️⃣Valgan(900mg BD)
These act by ❌ viral DNA polymerase
Pre-emptive Rx prevents development of near fatal #CMV disease. Mort for #CMV pneumonia ~60%
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Other FDA approved options:
1️⃣Foscarnet(90mg/kg)
2️⃣Cidofovir(5mg/kg/wk)
3️⃣Valgan(900mg BD)
These act by ❌ viral DNA polymerase
Pre-emptive Rx prevents development of near fatal #CMV disease. Mort for #CMV pneumonia ~60%
6/n
#CMV disease is a risk factor for sec bact/fungal infections aswell. Risk of invasive aspergillosis ⬆️7x
#CMV can become resistant to std Rx and when there is ⬆️DNAemia after 2 wks of therapy ➡️➡️➡️suspect resistance.
Pre-emptive Rx may ⬆️ risk of resistant CMV !
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#CMV can become resistant to std Rx and when there is ⬆️DNAemia after 2 wks of therapy ➡️➡️➡️suspect resistance.
Pre-emptive Rx may ⬆️ risk of resistant CMV !
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CMV mutations confer resistance:
UL97 ➡️➡️ Ganciclovir/Valgan resistance.
UL54 ➡️➡️ Foscarnet & Cidofovir resistance.
UL56 ➡️➡️ Letermovir resistance.
Risk fact for Resistant #CMV
1️⃣Prolonged anti CMV rx
2️⃣Inadequately dosed Rx
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UL97 ➡️➡️ Ganciclovir/Valgan resistance.
UL54 ➡️➡️ Foscarnet & Cidofovir resistance.
UL56 ➡️➡️ Letermovir resistance.
Risk fact for Resistant #CMV
1️⃣Prolonged anti CMV rx
2️⃣Inadequately dosed Rx
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Options to Rx resistant #CMV
1️⃣Reducing immunosuppression
2️⃣Ganciclovir +Foscarnet combination
3️⃣ CMV specific T cells
4️⃣ Maribavir/ Brincidofovir/ Letermovir/ Artesunate/Leflunomide
Maribavir➡️UL97 protein kinase inhibitor. Blocks nuclear egress of viral capsids.
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1️⃣Reducing immunosuppression
2️⃣Ganciclovir +Foscarnet combination
3️⃣ CMV specific T cells
4️⃣ Maribavir/ Brincidofovir/ Letermovir/ Artesunate/Leflunomide
Maribavir➡️UL97 protein kinase inhibitor. Blocks nuclear egress of viral capsids.
9/n
Since Ganciclovir/valgan act via UL 97 and marabivir ❌UL97, DON'T combine these agents.
Maribavir➡️well tolerated/ dysguesia+
Letermovir➡️terminase complex inhibitor. Not hepato/ renotoxic. Well tolerated.
FDA approved for prophylaxis in CMV sero+ patients post HSCT.
End.
Maribavir➡️well tolerated/ dysguesia+
Letermovir➡️terminase complex inhibitor. Not hepato/ renotoxic. Well tolerated.
FDA approved for prophylaxis in CMV sero+ patients post HSCT.
End.
@MatthewHoMD @DigambarPanchal @TheEBMT @EHA_Hematology @ASTCT @ASTCT_Journal @IndianYoungOnco @HemOncFellows @HCC_HemeCancer @BMTjournal @DrNeha90356702 @venkat_id
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