Portada Simposios - Supplements - Haematologica

XLII Reunión Nacional de la AEHH y XVI Congreso de la SETH. Simposios
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by Riddell and co-workers in Seattle have shown that
specific CTLs can be cloned in vitro, safely be given
to the patient, and their activity be detectable during
follow-up 13-15 . Preliminary data indicate that these
cells decrease the risk for development of CMV disease.
Recently new techniques such as the tetramer
technology have been developed that might allow
easier selection of CMV specific T-cells and several
laboratories are presently testing this strategy.
Human herpes virus type 6 (HHV-6)
HHV-6 exists in two subtypes that differ from each
other in 4-8 % of the DNA. Subtype B is the cause of
exanthema subitum in childhood and is the most
common cause for admission to hospital in infants
below one year of age. HHV-6 has been associated
with interstitial pneumonia, encephalitis, hepatitis,
and bone marrow suppression after stem cell transplantation.
Carrigan et al described two cases of interstitial
pneumonia in which HHV-6 could be isolated
from respiratory specimens and in one case
also from lung tissue 16 . HHV-6 has been implicated
as a cause of meningo-encephalitis in healthy children
and seems to have a propensity for the central
nervous system. Recently, Wang et al found HHV-6
as the cause of a large proportion of stem cell transplant
patients with encephalitis of “unknown origin”
17 . Carrigan et al showed a correlation between
post bone marrow transplant late marrow suppression
and presence of HHV-6 in the bone marrow
and a correlation between HHV-6 and rejection of a
marrow graft 18 . These observations have resulted in
that many transplant centers are actively investigating
the role of HHV-6 as a pathogen in allogeneic
stem cell transplant recipients. Ljungman et al has
recently shown that increased levels of HHV-6 DNA
is associated with delayed platelet engraftment and
an increased risk for HHV-6 associated disease such
as encephalitis (Ljungman et al, ICAAC 1999). There
has been no controlled studies of antiviral prophylaxis
against HHV-6 or therapy of HHV-6 associated
disease. Anecdotal reports have supported efficacy
of ganciclovir, foscarnet, and cidofovir in HHV-6 associated
disease.
Respiratory viruses
Respiratory viruses such as respiratory syncytial
virus (RSV), parainfluenza viruses, and influenza A
and B are widespread in the community with major
seasonal variations. Despite that these viruses are
so common it is only during recent years that their
role as pathogens in immunocompromised patients
has started to be appreciated. An important aspect
to consider regarding infections with respiratory viruses
is that these infections easily can be spread nosocomially
through immunocompetent staff and patient
relatives. The infections can be spread through
the air by droplets but more commonly is spread through
the hands of staff. Thus, infection control measures
are of major importance in the control of respiratory
infections.
Respiratory syncytial virus
RSV is a common infection and can be documented
during periods of high prevalence in the society
in up to 15 % of the patients 19,20 . The risk for development
of pneumonia in patients with upper respiratory
infection has varied but most studies show a
risk of approximately 30 %. RSV pneumonia is associated
with a high mortality. Harrington et al described
an outbreak at the Fred Hutchinson Cancer Research
Center in which 31 cases of RSV infections
were documented and the overall mortality was
45 % 19 . Eighteen patients developed pneumonia and
the mortality in patients with pneumonia was 78 %.
Whimbey et al presented 33 patients with an overall
mortality of 37 % 20 .
The treatment options are inhaled or intravenous
ribavirin with or without the addition of high dose
intravenous immune globulin. Since the mortality in
established pneumonia is high, one possible strategy
is preemptive therapy similar to what is common
practice in CMV infection to prevent the development
of pneumonia. This strategy can only be assessed
by a randomized study and such a study has
been ongoing for some time in the US but no data
is currently available.
The results of therapy in established pneumonia
have been poor. In the series by Harrington et al
13 patients with pneumonia were treated with aerosolized
ribavirin and four patients survived 19 . Whimbey
et al combined aerosolized ribavirin with high
titer anti-RSV immune globulin and showed that patients,
who were treated with the combination before
respiratory failure developed, had a mortality of
31 % 21 while patients who had therapy instituted
when ventilatory support was necessary had a mortality
of 100 %. Finally Sparrelid et al used in a small
number of patients the combination of aerosolized
and intravenous ribavirin with some early promising
results 22 . In a recent EBMT survey, the combination
of intravenous and inhaled ribavirin had the best
outcome (Ljungman et al unpublished results).
Parainfluenza viruses
The most common manifestation of parainfluenza
viruses is upper respiratory infection. It seems that
there are differences in virulence between different
subtypes, and parainfluenza virus type 3 seems to be
more virulent in that pneumonia is more common.
Ljungman et al described 11 cases with no mortality.
In this series two cases had parainfluenza 3, both developed
pneumonia but survived while nine patients
had parainfluenza 1 and all had mild and self-limiting
infections 23 . Wendt et al described 27 cases of
parainfluenza virus infections with a 22 % mortality
24 . Nineteen of 27 patients had parainfluenza
type 3. The frequency of pneumonia was 70 % and of