VZV−/HSV−
VZV−/HSV+
VZV+/HSV−/+
Autologous
No prophylaxis required
Acyclovir 800 mg po daily through day + 365
Acyclovir 800 mg po daily through day + 365
Allogeneic
No prophylaxis requireda
Acyclovir 800 mg po BID through day + 365 or off all immune suppression
Acyclovir 800 mg po BID through day + 365 or until off all immune suppression, whichever comes later
Table 10.2
Dosing recommendations for acyclovir and valacyclovir
Renal impairment | ||||
|---|---|---|---|---|
CrCl ≥ 50 mL/min | CrCl 30–49 mL/min | CrCl < 30 mL/min | ||
Acyclovir PO | Autologous Allogeneic | 800 mg po daily 800 mg po BID | 800 mg po daily 800 mg po daily | 400 mg po daily 400 mg po daily |
Valacyclovir PO | Autologous Allogeneic | 500 mg po daily 500 mg po BID | 500 mg po daily 500 mg po daily | 500 mg po daily 500 mg po daily |
Acyclovir IV | Autologous or allogeneic | 250 mg/m2 IV Q12H | 250 mg/m2 IV Q24H | 250 mg IV Q24H |
2.
If patient develops overt signs of oral or genital mucocutaneous herpes simplex virus (HSV) infection while on prophylactic dosing, increase to treatment doses of oral acyclovir (400 mg po 5×/day) or valacyclovir (500–1000 mg po twise daily (BID)) or change to acyclovir 5 mg/kg IV q8hr (adjusted for renal function).
3.
If symptoms persist despite therapeutic doses of acyclovir, consider the possibility of acyclovir-resistant HSV which may entail treatment with foscarnet or other approaches. In this instance, obtaining viral culture (for growth of an isolate) and resistance testing should be considered, along with consultation to the infectious diseases service.
4.
Varicella zoster virus (VZV)-seronegative allogeneic recipients who are < 24 months post-transplant, > 24 months post-transplant and on immunosuppressive therapy or who have active chronic graft-versus-host disease (GVHD)* , who have had close contact with a person with either primary VZV infection (chickenpox) or herpes zoster (shingles) should receive VZV-specific immunoglobulin as soon as possible for up to 10 days following the exposure. VariZIG® (Cangene Corporation, Winnipeg, Canada) is a purified human varicella zoster immune globulin preparation. If VariZIG® cannot be obtained, consider IV immunoglobulin 400 mg/kg × 1 dose, although the data to support efficacy are limited.
*Note: These patients are not candidates for postexposure varicella immunization as it is a live attenuated virus vaccine.
5.
Family members and close contacts who receive the Varivax® or Zostavax® vaccine and develop a rash within 3–6 weeks after vaccination should avoid contact with the hematopoietic stem cell transplantation (HSCT) recipient to decrease risk for transmission of vaccine-strain virus.
6.
If a transplant recipient is hospitalized with or develops VZV infection during hospitalization (either primary infection or reactivation infection with or without dissemination), isolation should consist of contact and airborne precautions in a negative airflow room to limit the risk for transmission on the transplant unit. Placement off the transplant ward should be considered.
10.2 Cytomegalovirus Disease Prevention
1.
HSCT candidates who are cytomegalovirus (CMV)-seronegative should receive either CMV serongative or leukocyte-reduced blood products to decrease the risk of primary CMV infection. In this setting, a CMV-seronegative donor is preferred if other factors (e.g., human leukocyte antigen (HLA) match, etc.) are equal.
2.
Autologous recipients: No CMV surveillance is required for unselected autologous recipients, unless clinically indicated (e.g., patients with protracted fevers, gastrointestinal (GI) symptoms). If patient has documented CMV disease within 1 year prior to transplant, CMV polymerase chain reactions (PCRs) should be followed weekly through day + 100.
a.
CMV-seropositive autologous recipients who have received major T cell suppression prior to HSCT (e.g., alemtuzumab) , total body irradiation as part of the conditioning regimen, high-dose corticosteroids for another indication, and/or T cell depleted (CD34 + selected) grafts are at risk for symptomatic CMV infection or disease and should have preemptive monitoring post–transplant.
3.
Allogeneic recipients: Both prophylactic and preemptive strategies can be used to prevent CMV disease in allogeneic recipients. A preemptive approach is used most commonly, but prophylaxis is undertaken by some centers and in certain circumstances, particularly for high-risk patients such as recipients of cord blood or haploidentical products.
a.
Given the poor outcomes associated with CMV disease prior to allogeneic transplantation, patients with documented pre-transplant CMV infections warrant special consideration with regard to preemptive monitoring strategies, and even consideration for prophylaxis in some settings.
4.
For preemptive monitoring, CMV DNA viral load is the standard test, supplanting CMV pp65 antigenemia which has its limitations in the setting of leukopenia. Ideally, measurement of CMV DNA should be with the international reference standard to decrease inter-laboratory variability.
5.
Preemptive monitoring should occur with sufficient regularity so as to allow time for intervention prior to the onset of CMV end-organ disease.
6.
At our center, we use the following protocol for preemptive monitoring:
a.
Patients who are CMV-seronegative with a CMV-seronegative donor should have monthly CMV PCRs through day + 100, and when clinically indicated (e.g., if protracted fevers, GI symptoms, unexpected cytopenias, etc.).
b.
Patients who are CMV-seropositive or who have a CMV-seropositive donor should have weekly CMV PCRs through day + 100.
c.
Any patient with CMV infection prior to or after day + 100 should have prolonged surveillance.
i.
If no GVHD is present, continue surveillance weekly for 3 months following infection, then every other week for 3 months.
ii.
If GVHD is present, continue surveillance weekly for 1 year following CMV infection.
7.
Preemptive therapy is typically initiated after the detection of CMV DNA (or antigenemia); it should be recognized, however, that there are no standardized or validated thresholds. Prophylactic acyclovir should be discontinued if preemptive therapy for CMV infection is initiated.
8.
While there is a growing literature to support the safety and efficacy of oral valganciclovir as an approach to preemptive therapy in HSCT recipients, IV ganciclovir or foscarnet remain the guideline recommendation at this writing.
9.
Chest X-ray should be performed at the time of documentation of CMV reactivation, with finer imaging reserved for symptomatic presentation.
10.
At our center , we incorporate oral valganciclovir as preemptive therapy for any patient without signs/symptoms suggestive of CMV end-organ disease and meeting all of the following criteria:
a.
No signs/symptoms or suspicion of CMV end-organ disease
b.
Normal chest X-ray
c.
Absence of GI complaints (nausea, vomiting, diarrhea)
d.
Afebrile
e.
CMV viral load < 5000 copies/mL
f.
No history of medication noncompliance
g.
Able to tolerate adequate oral intake/medications
h.
No evidence of active gut GVHD
i.
Get Clinical Tree app for offline access
Preemptive valganciclovir consists of induction dosing until quantitative PCR assays are negative for two consecutive weeks, then maintenance dosing for 2 weeks (renal dose adjustment as indicated, outlined in Table 10.3).
Table 10.3
Dosing recommendations for valganciclovir in renal impairment
Normal renal function | Renal impairmenta | ||||
|---|---|---|---|---|---|
CrCl | ≥ 60 mL/min | 40–59 mL/min | 25–39 mL/min | 10–24 mL/min | < 10 mL/min (hemodialysis) |
Induction | 900 mg po BID | 450 mg po BID | 450 mg po daily | 450 mg po QOD | Do not use |
Maintenance | 900 mg po daily | 450 mg po daily | 450 mg po QOD | 450 mg po twice weekly | Do not use–no dosing guidlines available |
aPatients with renal insufficiency should receive valganciclovir 900mg po BID x 2 doses. The dose should then be adjusted for their renal function as outlined in Table 10.4 BID twice daily. QOD every other day.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree