H e m a t o lo g y E d u c a t io n - European Hematology Association

port have also been used. 5 Combination therapy has
been used anecdotally but no clear assessment can be
made of its efficacy.
Organ toxicity is another potential limitation to
effective drug treatment. Ganciclovir is well known to
cause neutropenia in approximately one-third of HCT
recipients. Strategies that have been proposed include
holding the drug (only recommended when viral load is
completely suppressed), switching to foscarnet, or continuation
of ganciclovir with concomitant use of
hematopoietic growth factors. Hematopoietic growth
factors generally lead to a faster recovery of neutrophil
counts when used earlier during the course of neutropenia.
We start growth factors when the absolute
neutrophil count drops below 1000/mm 3 and start foscarnet
concurrently if the patient is still viremic. 5,37 If a
switch to foscarnet is not possible, for example, due to
renal insufficiency, we would consider initiating
growth factors even earlier while the patient is still
receiving ganciclovir. It should be noted that none of
these strategies have been tested in randomized trials.
Herpes simplex virus and varicella zoster virus
Treatment of HSV and VZV disease has become less
common with effective prophylaxis available.
Treatment of wild-type disease caused by HSV and
VZV is with acyclovir or valacyclovir. 2 Disseminated
VZV disease is a potentially life-threatening condition
that should be treated aggressively with high-dose
intravenous acyclovir. Abdominal VZV disease is a
medical emergency. It can present without skin manifestations,
is characterized by severe abdominal pain
and rapidly rising transaminases, and may be associated
with inappropriate antidiuretic hormone secretion. 38
Acyclovir prophylaxis at the appropriate dose and
when given for prolonged time, effectively prevents
both wild-type VZV and HSV disease; drug-resistant
HSV disease was also reduced with this regimen. 39,40
Acyclovir resistant disease typically respond to foscarnet.
41 Cidofovir has been used in selected cases but no
larger series have been reported.
EBV, Human herpes viruses 6, 7, and 8
EBV can cause viremia and lymphoproliferative disease
(PTLD) in HCT recipients, mainly in patients with
severe T cell immunosuppression. Screening for
viremia and early treatment with rituximab appears to
be beneficial in high-risk settings. 4,9 There is no evidence
that antiviral treatment is effective in this setting.
PTLD may also be treated with rituximab, but
chemotherapy may also be required 9 (Table 1). EBV
specific T cell therapy showed promising initial results
and is presently being investigated at selected transplant
centers. 9 HHV-6 disease can cause encephalitis,
which occurs early after HCT in most cases. 42 Recently,
HHV-6 has also been independently associated with
delirium and neurocognitive decline after HCT. 43 Both
ganciclovir and foscarnet have been used in clinical
practice but no randomized trial exists (Table 1).
Cidofovir also has activity in vitro against HHV-6 but
larger series on its use in patients have not been reported.
We treat HHV-6 disease with prolonged courses of
induction dosing (i.e., 3 weeks) followed by maintenance
dosing for at total of 4–6 week or until resolution
London, United Kingdom, June 9-12, 2011
of symptoms and suppression of viral load is achieved.
Complications due to HHV-7 and 8 appear to be very
rare in HCT recipients.
Polyomaviruses
BK virus
BK virus shedding is highly prevalent early after
HCT. Some patients develop BK-associated hemorrhagic
cystitis, which is usually associated with high viral
load in both urine and blood. 44 BK virus nephritis has
also been described. No proven treatment exists.
Cidofovir has been used in both low-dose (0.5-0.10
mg/kg/week) and regular dose regimens (5
mg/kg/week) but no conclusive evidence exists that
this treatment is superior to supportive care 45 (Table 1).
Leflunomide has also been shown to reduce viral load
in some studies but not in others, 46-48 however, no systematic
controlled evaluation of its therapeutic effect
(alone or in combination) has been published.
Reduction of immunosuppression is generally recommended
in kidney transplant recipients. 44 Whether this
approach is effective in HCT recipients has not been
systematically examined; however, it seems reasonable
to attempt reduction if feasible.
JC virus
JC virus is the cause of progressive multi-focal
leukoencephalopathy in immunosuppressed patients.
No proven treatment exists. Cidofovir has activity in
vitro, but a study in HIV infected individuals failed to
show therapeutic benefit. No data exists in HCT recipients.
49 Drugs that have been in individual patients with
variable success include IL-2, cytarabine, chlorpromazine,
or the antipsychotic drugs ziprasidone, risperidone,
and olanzapine. 50-52 CMX-001 also shows activity
in vitro.
Hepatitis viruses
Treatment guidelines for hepatitis viruses are complex.
Therefore, treatment should be coordinated with
specialists in infectious diseases or hepatology who are
familiar with the treatment of chronic viral liver disease.
4 The following summary includes selected aspects
of viral hepatitis management from a well-referenced
recent summary by an international expert panel that
has been endorsed by several professional societies,
including the American Society for Blood and Marrow
Transplantation, the European Blood and Marrow
Transplant group, the Infectious Disease Society of
America, the US Center for Disease Control and Pre -
vention among others 4 (Table 1).
Hepatitis B
Management of hepatitis B involves assessment of
both the donor and recipient serostatus, often accompanied
by viral load determinations, if the donor is
HBV. 4 Recipients of HBV DNA positive transplant products
should receive post transplant antiviral prophylaxis
though 6 months after discontinuation of immunosuppression;
if, at the time of harvest, both the donor and
Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 333 |