Thread by @nihardesai7

Humanity has always struggled to fight #viruses , best exemplified by the ongoing #Covid_19 #pandemic ,so I thought of doing a thread on a #virus which frequently troubles #hematology patients

It's called #CMV or #HHV5
It wrecks havoc #posttransplant

#MedTwitter @BloodJournal

⚡DNA virus ,1 of the MC infections post SCT

⚡It has the largest genome of any known human virus [230kb /200 genes]

⚡Most humans harbour latent CMV, infection MC aquired in childhood.

⚡Site of latency in humans- Not Known
In murine models - hepatic sinusoidal cells

⚡The risk of reactivation depends on CMV sero status and is as follows:
D-/R+ > D+/R+ > D+/ R- > D- / R -

⚡The other risk factors are
1️⃣ T cell depletion
2️⃣ HaploSCT
3️⃣ UCB SCT
4️⃣ GVHD requiring Rx

⚡ So why not give prophylaxis to these patients ??

⚡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 ??

⚡No set guideline. The threshold depends on the patient serostatus and other risk factors.

⚡Lack of standardized reporting further compounds the problem.

⚡But >500copies/ml before D100 must trigger pre-emptive therapy.

⚡1st line pre-emptive Rx➡️➡️ Ganciclovir

⚡Other FDA approved options
1️⃣ Foscarnet(1991)
2️⃣ Cidofovir (1996)
3️⃣ Valgan.(2001)

⚡These act by ❌ viral DNA polymerase

⚡ Pre-emptive Rx prevents development of near fatal #CMV disease. Mort for #CMV pneumonia ~60%

⚡#CMV disease is a risk factor for sec bact/fungal infections aswell. Risk of asper ⬆️7x

⚡#CMV can become resistant to std Rx and when there is ⬆️DNAemia after 2 wks of therapy ➡️➡️➡️suspect resistance.

⚡CMV mutations confer resistance:
UL97 ➡️➡️ Ganciclovir/Valgan resistance
UL54 ➡️➡️ Foscarnet & Cidofovir resistance
UL56 ➡️➡️ Letermovir resistance

⚡Risk fact for Resistant #CMV
1️⃣ Prolonged anti CMV rx
2️⃣ Inadequately dosed Rx

⚡Options to Rx resistant #CMV
1️⃣ Reducing immunosuppression
2️⃣ Ganciclovir + Foscarnet combination
3️⃣ CMV specific T cell infusions
4️⃣ Maribavir / Brincidofovir / Letermovir

⚡Maribavir➡️UL97 protein kinase inhibitor. Blocks nuclear egress of viral capsids.

⚡Maribavir➡️well tolerated / dysguesia ++

⚡Letermovir➡️terminase complex inhi. Not hepato or renotoxic . Promising prophylactic agent.

@BloodAdvances @BMTjournal
@iNDUSBMT @IJMPOofficial
@faheema_hasan @sujeethemat @SujayRainchwar @satya_yadav @SChellapuram @young_eha