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

16 th Congress of the European Hematology Association
For RSV lower respiratory tract disease, the best outcomes
have been reported with aerosolized ribavirin
while systemic ribavirin alone does not seem to be
effective; 19,20 better response rates with systemic ribavirin
have been described for treatment of RSV URI;
however, small samples sizes limit the strength of the
data. 17,21 Whether concomitant intravenous
immunoglobulin or RSV-specific immunoglobulin or
palivizumab, an RSV-specific monoclonal antibody, is
beneficial has not been studied in a randomized fashion.
There are some suggestions from uncontrolled data
that high-titer antibody preparations or palivizumab is
associated with better outcomes than pooled
immunoglobulin preparations; 22-24 however, the
strength of the evidence is low. Overall, outcome
results from different sites are highly variable due to a
long list of factors that are likely to affect outcome,
including the timing of initiation of therapy, the presence
of lymphopenia at the time of diagnosis, presence
of co-pathogens (e.g., invasive moulds, CMV), and the
use of immunosuppressive agents.
Influenzaviruses
Influenza can cause series disease after HCT. Both
seasonal and the recent pandemic H1N1 strain can lead
to lower respiratory tract disease and death. 25
Fortunately, antiviral drugs are widely available and
largely effective, although drug resistance is a potential
problem and may differ between circulating strains. 26
Generally, all influenza cases, both upper and lower
respiratory tract disease, should be immediately treated.
There is evidence that early treatment is more effective
but even treatment that is started after 2 days
appears to be effective. 25,27 Treatment aspects have
recently been reviewed by Casper et al. 6 Perhaps the
most interesting question is whether combination therapy
(e.g., a combination of neuraminidase inhibitors
with M2 inhibitors and ribavirin, or other combinations)
is beneficial in the immunocompromised
patients. Also, the role of adjunctive use of corticosteroids
has been raised by studies that suggested a
potential beneficial effect in lower respiratory tract disease.
25,27 These studies were done retrospectively and
examined steroids that were given for the treatment of
graft versus host disease, however, the results are
provocative and should trigger further investigations.
Given the high virulence of the pandemic H1N1 strain,
more aggressive approaches are urgently needed. Thus,
randomized trials of combination therapy, higher dose
regimens, and adjunctive use of corticosteroids are
needed.
Parainfluenzaviruses PIV
Approximately 10% of patients acquire PIV after
HCT. 28 PIV can cause fatal pneumonia and late airflow
obstruction, especially following lower respiratory tract
disease. 29 One study reported an association of highdose
systemic steroids with progression to lower respiratory
tract disease. 30 Aerosolized ribavirin for lower
respiratory tract disease was unsuccessful in one retrospective
analysis. 30 Oral ribavirin has been used in small
series for both upper and lower respiratory tract disease
(Table 1). 31 Overall, the data are difficult to interpret
due to the retrospective nature of the studies and the
small sample sizes. However, we attempt to reduce
imnunosuppression and provide oral ribavirin for lower
respiratory tract disease.
Human metapneumovirus HMPV
HMPV occurs in up to 5% of HCT recipients and can
cause serious lower respiratory tract disease. 32 There is
no proven treatment for HMPV disease. Intravenous
immunoglobulin effectively neutralizes HMPV in vitro,
however, its effect in vivo is unknown. 33 Ribavirin is
active in vitro; 33 however, whether this translates into
therapeutic benefit in patients is unknown.
Human rhinoviruses HRhV
HRhV is the most common respiratory virus infection
after HCT. Most infections are restricted to the
upper respiratory tract but serious lower respiratory
tract disease can occur occasionally. 34 No specific antiviral
treatment exists.
Other respiratory viruses
Several new viruses have been discovered recently,
including several coronaviruses, human bocavirus, and
the polyomaviruses WU and KI. No clear evidence of
disease association has been reported to date; 35 however,
studies are ongoing to further examine possible disease
associations of these viruses in the HCT setting.
No specific antiviral treatment exists for these viruses.
Herpesviruses
Cytomegalovirus
CMV continues to be a challenge, although preemptive
treatment strategies have been optimized over the
past decade. A recent large multicenter randomized
trial showed CMV disease rates of less than 3% with
pp65 antigenemia and PCR-guided preemptive therapy
during the first 100 days after HCT. 36 In the same trial,
a novel drug, maribavir, failed to be effective in preventing
CMV antigenemia or DNAemia at a dose of
100 mg twice daily. Treatment problems arise when
the patient develops endorgan CMV disease, and
include primary refractory disease (mainly with CMV
pneumonia), drug resistance, and the inability to use
available drugs due to renal insufficiency or neutropenia.
A detailed description of current management
options has recently been published. 5
Drug resistance continues to be infrequent but may
be a formidable management problem if it occurs.
Resistance to ganciclovir is more commonly observed
than that to other drugs due to the prominent role this
drug plays in CMV management; however, resistance
to foscarnet and cidofovir can occur as well. Typically,
drug resistance occurs in a setting of prolonged and/or
repeated antiviral drug exposure and incomplete suppression
of viral load. 5 This scenario is most common in
situations of severe immunosuppression and/or low
antiviral dose regimens. Management includes molecular
testing when resistance is suspected, switching to an
alternative antiviral drug, and reduction of immunosuppression
if possible. In case of ganciclovir resistance,
dose increases with hematopoietic growth factor sup-
| 332 | Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1)