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The viruses behind cold sores and shingles stay in the body for life and can flare when cancer treatment weakens the immune system. People having intensive leukaemia treatment, a stem cell transplant, or myeloma drugs such as bortezomib are usually given an antiviral tablet, aciclovir or valaciclovir, to prevent this. Most people having ordinary chemotherapy for a solid tumour do not need it.
ASCO/IDSA (2018) recommend nucleoside analogue prophylaxis such as aciclovir for HSV-seropositive patients having allogeneic stem cell transplant or leukaemia induction. AGIHO (2022, adults) recommends oral aciclovir 400 mg twice or four times daily against oral HSV disease (AIIr), valaciclovir as an alternative (BI), and intravenous aciclovir 250 mg/m2 three times daily if oral medication is not tolerated (AIIr). Against VZV, oral aciclovir from 400 mg once daily to 400 mg three times daily (AII). Indications: acute leukaemia on intensive chemotherapy, from induction through neutropenia (BIIr); ALL throughout treatment (BI); acute promyelocytic leukaemia on arsenic trioxide, during treatment and 6 months after (BIIr); any proteasome inhibitor-based myeloma regimen, bortezomib strongly (AII); idelalisib (BIII); selected lymphoma and CLL by individual risk. Not generally indicated for VZV in solid tumours (DIII), where 5-year cumulative zoster incidence is about 5%; consider it with long-term corticosteroids (CIIu), continued up to 6 months after steroids stop. Serology is optional because about 90% of adults are HSV-1 and VZV seropositive, so universal prophylaxis is equally appropriate. Recombinant (non-live) zoster vaccine is recommended, with aciclovir still added in high-risk groups until comparative data exist; live zoster vaccine is contraindicated. All three nucleoside analogues need dose adjustment in renal impairment. Brivudin is contraindicated with fluoropyrimidines.
Why: Without it, herpes simplex flares in a third to two thirds of people on intensive leukaemia treatment, mostly as painful mouth ulcers.
“Herpes simplex virus-seropositive patients undergoing allogeneic hematopoietic stem-cell transplantation or leukemia induction therapy should receive nucleoside analog-based antiviral prophylaxis, such as acyclovir.”
Why: About nine in ten adults already carry these viruses, so testing first changes the decision for few people.
“We consider a universal prophylactic strategy for all patients with indication for prophylaxis of HSV as equally appropriate, because seroprevalence of HSV-1 is about 90% for adults.”
Why: In trials aciclovir cut symptomatic herpes simplex to a tenth of the rate with placebo.
“Considering the high risk of reactivation prophylactic acyclovir or valacyclovir should be applied in patients with acute leukaemia receiving intensive chemotherapy to reduce HSV stomatitis, and to reduce other HSV reactivations (BIIr) (Table 6).”
Why: A network analysis of thirteen trials found these the most effective regimens, and twice daily worked almost as well as four times daily.
“We recommend oral acyclovir 400 mg BID or 400 mg QID as prophylaxis of oral HSV disease (AIIr).”
Why: ALL treatment is long and includes steroids and sometimes anti-CD20 antibodies, all of which raise the risk.
“antiviral prophylaxis to reduce reactivation of HSV and VZV is recommended for patients with acute lymphoblastic leukaemia while on treatment (BI) (Table 6).”
Why: Shingles affected 13% of people on bortezomib in the VISTA trial, and about 3% when they also took an antiviral.
“Therefore, we strongly recommend acyclovir prophylaxis in patients receiving bortezomib-based treatment regimens (AII) (Table 7).”
Why: All these doses have worked; no trial has compared them.
“We recommend oral acyclovir to reduce clinical VZV reactivation; dosages from 400 mg once daily to 400 mg TID have been shown to be effective (AII).”
Why: Without prophylaxis only about 5 in 100 people with solid tumours get shingles within five years.
“Pharmacological prophylaxis to prevent disease by reactivation of VZV in patients with solid tumours is not generally indicated (DIII) (Table 5).”
Why: Steroids at 10 mg prednisolone a day or more for two weeks or longer raise the risk of shingles.
“Antiviral prophylaxis might be continued for up to 6 months after corticosteroids have been terminated [76].”
Why: The vaccine is safe in cancer but works less well during treatment, and no trial has yet shown it can replace the tablet.
“Until more data are available, particularly of comparative trials for vaccination versus pharmacological prophylaxis, it is suggested to apply acyclovir additionally in high risk patient groups (for recommendations see below).”
Why: All three are cleared by the kidneys and build up when kidney function is poor.
“Of note, all three nucleoside analogues (acyclovir, valacyclovir, famciclovir) require dose adjustment in patients with renal impairment.”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
ASCO/IDSA (2018) and AGIHO (2022) agree that HSV prophylaxis with aciclovir belongs in leukaemia induction and allogeneic transplant. AGIHO is the more detailed and more recent: oral aciclovir 400 mg twice or four times daily for HSV (AIIr), 400 mg once to three times daily for VZV (AII), for intensive leukaemia treatment, ALL throughout therapy, arsenic trioxide in acute promyelocytic leukaemia, and every proteasome inhibitor regimen in myeloma, but not routinely for solid tumours (DIII). The recombinant zoster vaccine is recommended but does not yet replace aciclovir in high-risk groups. Duration is the main unsettled point: AGIHO gives 28 to 100 days in AML trials, the whole of ALL treatment, 6 months after arsenic trioxide or after steroids, and individual extension in lymphoma where reactivations occurred up to 51 months after treatment began.
AGIHO/DGHO, Annals of Hematology 2022 · ASCO and IDSA, Journal of Clinical Oncology 2018
Where it differs: Uses valaciclovir, a better absorbed prodrug, at 250 or 500 mg twice daily for HSV, or for VZV in myeloma.
Evidence: AGIHO grades valaciclovir for HSV BI, and for VZV CIIu in general and BIIu with proteasome inhibitors; the best valaciclovir dose for HSV is not defined.
Where it differs: Uses 400 mg once daily, or lower, for shingles prevention during bortezomib, carfilzomib or ixazomib.
Evidence: Mainly retrospective series; AGIHO's 2015 edition noted that the risk of aciclovir resistance with low doses has not been assessed.
AGIHO/DGHO, Annals of Hematology 2022 · AGIHO/DGHO, Annals of Hematology 2015
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Oral aciclovir 400 mg twice or four times daily against oral HSV disease | AIIr | AGIHO/DGHO, Annals of Hematology 2022 |
| Valaciclovir as an alternative against oral HSV disease “Oral valacyclovir can be used alternatively (BI), but the best regimen (250 mg BID or 500 mg BID) has not yet been defined.” | BI | AGIHO/DGHO, Annals of Hematology 2022 |
| Prophylaxis in acute leukaemia on intensive chemotherapy | BIIr | AGIHO/DGHO, Annals of Hematology 2022 |
| Prophylaxis in ALL throughout treatment | BI | AGIHO/DGHO, Annals of Hematology 2022 |
| Aciclovir with bortezomib-based regimens | AII | AGIHO/DGHO, Annals of Hematology 2022 |
| No routine VZV prophylaxis in solid tumours | DIII | AGIHO/DGHO, Annals of Hematology 2022 |
| Consider prophylaxis with long-term high-dose corticosteroids | CIIu | AGIHO/DGHO, Annals of Hematology 2022 |
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