CMV after hematopoietic stem cell transplantation: Difference between revisions

Latest revision as of 21:21, 19 September 2020

Background

Reactivation of latent recipient CMV infection is common after hematopoietic stem cell transplantation

Microbiology

Refer to Cytomegalovirus

Epidemiology

Reactivates in 60 to 70% of CMV-seropositive patients and primary infection affects 20 to 30% of seronegative recipients who have seropositive donors

Donor	Recipient	Risk
±	+	60-70%
+	–	20-30%
–	–	5%

Risk is proportional to the amount of T cell dysfunction, so risk is higher earlier in disease and after fludarabine, alemtuzumab, or 2-chlorodeoxyadenose
GVHD is another important risk factor

Clinical Manifestations

With monitoring and preemptive therapy, CMV pneumonitis has decreased to 5% of seropositive allogeneic recipients
Pneumonitis (63%)
Enteritis (26%)
Retinitis (5%)
Increased risk of rejection

Management

Prophylaxis

Now commonly done with letermovir, started within 28 days of transplantation

Preemptive Therapy

Most frequently managed with weekly viral loads and preemptive treatment (PET) at a lab-specific threshold
Antiviral treatment follows a model of induction therapy for 14 days; if it has declined by at least 1 log, then step down to lower-dose maintenance therapy until viremia resolves fully; otherwise, continue induction dosing
- Induction therapy
  - Ganciclovir 5 mg/kg q12h
  - If concerns about resistance or bone marrow suppression, foscarnet 90 mg/kg IV q12h
- Maintenance therapy
  - Valganciclovir 900 mg po daily
  - If concerns about oral absorption, continue ganciclovir 5 mg/kg IV q24h
  - If concerns about resistance or bone marrow suppression, foscarnet 90 mg/kg IV q24h
Use CMV safe (leukoreduced or filtered) blood products if the recipient is CMV seronegative

Serostatus	Blood products	Duration of PET
D-/R-	CMV safe	weeks 2 to 12
D+/R-	CMV safe	weeks 2 to 12
autologous R-	CMV safe	weeks 2 to 5
D±/R+	CMV untested	weeks 2 to 12, then q2-4wk until week 26
autologous R+	CMV untested	weeks 2 to 5

CMV Disease

Treatment is with ganciclovir induction for 14 to 21 days with IVIG 500 mg/kg every other day, followed by maintenance ganciclovir for at least 3 to 4 weeks
May need to continue maintenance for longer if patient has GVHD, enteritis with deep ulcerations, or retinitis

@@ Line 1: / Line 1: @@
-== Management ==
+== Background ==
-* Most frequently managed with weekly viral loads and preemptive treatment (PET) at a lab-specific threshold
+* Reactivation of latent recipient [[CMV]] infection is common after [[hematopoietic stem cell transplantation]]
-* Antiviral treatment:
-** [[Is treated by::ganciclovir]] 5 mg/kg q12h for 7 to 14 days (induction) followed by [[Is treated by::valganciclovir]] 900 mg po daily (maintenance) until a few weeks after viremia resolves
+=== Microbiology ===
-** If concerns about oral antiviral, would continue [[Is treated by::ganciclovir]] 5 mg/kg IV daily (maintenance)
-** If ganciclovir resistance, next step is [[Is treated by::foscarnet]] 90 mg/kg IV q12h (induction) followed by q24h (maintenance)
+* Refer to [[Cytomegalovirus#Microbiology|Cytomegalovirus]]
-** Major adverse effect of ganciclovir is bone marrow suppression
-* Use CMV safe (leukoreduced or filtered) blood products if the recipient is CMV seronegative
+=== Epidemiology ===
+* Reactivates in 60 to 70% of CMV-seropositive patients and primary infection affects 20 to 30% of seronegative recipients who have seropositive donors
+{| class="wikitable"
+!Donor
+!Recipient
+!Risk
+|-
+|±
+| +
+|60-70%
+|-
+| +
+|–
+|20-30%
+|-
+|–
+|–
+|5%
+|}
+* Risk is proportional to the amount of T cell dysfunction, so risk is higher earlier in disease and after [[fludarabine]], [[alemtuzumab]], or [[2-chlorodeoxyadenose]]
+* GVHD is another important risk factor
+==Clinical Manifestations==
+*With monitoring and preemptive therapy, CMV pneumonitis has decreased to 5% of seropositive allogeneic recipients
+*[[Pneumonitis]] (63%)
+*[[Enteritis]] (26%)
+*[[Retinitis]] (5%)
+*Increased risk of rejection
+==Management==
+=== Prophylaxis ===
+* Now commonly done with [[letermovir]], started within 28 days of transplantation
+===Preemptive Therapy===
+*Most frequently managed with weekly viral loads and preemptive treatment (PET) at a lab-specific threshold
+*Antiviral treatment follows a model of induction therapy for 14 days; if it has declined by at least 1 log, then step down to lower-dose maintenance therapy until viremia resolves fully; otherwise, continue induction dosing
+**Induction therapy
+***[[Is treated by::Ganciclovir]] 5 mg/kg q12h
+***If concerns about resistance or bone marrow suppression, [[Is treated by::foscarnet]] 90 mg/kg IV q12h
+**Maintenance therapy
+***[[Is treated by::Valganciclovir]] 900 mg po daily
+***If concerns about oral absorption, continue [[Is treated by::ganciclovir]] 5 mg/kg IV q24h
+***If concerns about resistance or bone marrow suppression, [[Is treated by::foscarnet]] 90 mg/kg IV q24h
+*Use CMV safe (leukoreduced or filtered) blood products if the recipient is CMV seronegative
 {| class="wikitable sortable"
-! Serostatus
+!Serostatus
-! Blood products
+!Blood products
-! Duration of PET
+!Duration of PET
 |-
-| D-/R-
+|D-/R-
-| CMV safe
+|CMV safe
-| weeks 2 to 12
+|weeks 2 to 12
 |-
-| D+/R-
+|D+/R-
-| CMV safe
+|CMV safe
-| weeks 2 to 12
+|weeks 2 to 12
 |-
-| autologous R-
+|autologous R-
-| CMV safe
+|CMV safe
-| weeks 2 to 5
+|weeks 2 to 5
 |-
-| D±/R+
+|D±/R+
-| CMV untested
+|CMV untested
-| weeks 2 to 12, then q2-4wk until week 26
+|weeks 2 to 12, then q2-4wk until week 26
 |-
-| autologous R+
+|autologous R+
-| CMV untested
+|CMV untested
-| weeks 2 to 5
+|weeks 2 to 5
 |}
+===CMV Disease===
+*Treatment is with [[Is treated by::ganciclovir]] induction for 14 to 21 days with IVIG 500 mg/kg every other day, followed by maintenance [[ganciclovir]] for at least 3 to 4 weeks
+*May need to continue maintenance for longer if patient has [[GVHD]], enteritis with deep ulcerations, or retinitis
 [[Category:Immunocompromised hosts]]