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

M. Boeckh
Vaccine and Infectious Disease
Division and Clinical Research
Division, Fred Hutchinson Cancer
Research Center, and Department
of Medicine, University
of Washington, Seattle, OR, USA
Funding: This work was partially
supported by NIH grants CA18029,
CA15704, and HL93294.
M.B. received research funding from
Viropharma Inc., Chimerix Inc., Vical
Inc., Roche Pharmaceuticals, Glaxo-
Smith-Kline, and Adamas
Pharmaceuticals, served as a consultant
for Novartis, Astellas, Gilead,
Chimerix Inc., Vical Inc., Boehringer
Ingelheim, and Roche/Genentech.
He served on DSMBs for Pfizer and
for an influenza vaccine study funded
byUS Government funds from the
Office for Preparedness and
Response, Biomedical Advanced
Research and Development
Authority, under contract to DynPort
Vaccine Company.
Hematology Education:
the education program for the
annual congress of the European
Hematology Association
2011;5:330-336
Supportive care of transplants
Treatment of viral infections after hematopoietic
cell transplantation
Introduction
Viral infections are a major complication
after hematopoietic cell transplantation
(HCT). Patients are at risk for complications
of viruses that reactivate from latency (e.g.,
herpes viruses), as well as those that are
acquired exogenously (e.g., respiratory
viruses). Major progress has been made in
the management of cytomegalovirus, historically
the most deadly of all viruses, but
challenges remain with effective management
of a large spectrum of viral disease.
This review will summarize recent developments
in the treatment of viral diseases.
Prophylactic strategies are not reviewed
here. The reader is also referred to published
guidelines that have recently been endorsed
by a wide range of international professional
societies, 1-4 as well as recently published
comprehensive reviews of management
options for the most relevant viruses,
including cytomegalo virus (CMV), Epstein–
Barr Virus (EBV), influenza virus, adenovirus,
and respiratory syncytial virus. 5-9
Due to a paucity of randomized trials, many
treatment recommendations are based on
expert opinion.
Adenoviruses
Adenovirus disease is an emerging problem
in HCT recipients. Disease occurs mainly
in patients with profoundly reduced T
cell function (i.e., following in vivo or ex vivo
T cell depletion) but sporadic cases in non-T
cell depleted patients can occur. 10 The outcome
is often fatal, especially in the presence
of low lymphocyte counts. 10 Treatment
options are very limited and consist presently
of cidofovir and ribavirin. No randomized
trial has been performed and neither drug is
approved for this indication. Presently, cidofovir
is considered the treatment of choice. 8
A B S T R A C T
Viral infections are important complications after hematopoietic cell transplantation. Progress has
been made in the management of cytomegalovirus and other herpes viruses, as well as influenza.
However, for many viral diseases, there are either no or only moderately active treatment options
available. This review will provide an overview of currently available treatment options and define
areas of need for future development of therapeutics.
(Table 1). Two dose regimens are available,
that is, 5 mg/kg once a week or 1 mg/kg
three times per week. 11,12 The latter may be
less toxic but does not cover CMV. Ribavirin
treatment has shown variable results, possibly
due to strain-specific susceptibilities. We
occasionally use a trial of ribavirin in addition
to cidofovir or by itself in salvage situations
with close viral load monitoring.
Reduction of immunosuppression should be
attempted given the strong correlation of
lymphocyte recovery with outcome; 8 however,
this is often not feasible. A newer compound
(i.e., CMX-001, Chimerix Inc.) with
potentially higher activity, and an improved
toxicity profile is presently under investigation.
13,14 Treatment with donor-derived adenovirus-specific
T cells is being studied at
several centers. 8
Respiratory viruses
Respiratory syncytial virus RSV
RSV pneumonia carries a high mortality
in highly immunosuppressed HCT recipients.
However, recovery from RSV lower
respiratory tract disease without specific
treatment has also been reported. 15 Un -
fortunately, treatment recommendations are
based almost entirely on non-randomized
clinical trials. Only one small randomized
trial has been conducted. 16 Thus, most of the
recommendations here are based on our
experience and some larger published retrospective
series. Early treatment of RSV
upper respiratory tract infection has been
advocated by several experts, 1 especially in
the presence of lymphopenia (which is a significant
risk factor for progression) or in
other high risk situations. 17 This strategy
was moderately effective in one large retrospective
review. 18
The data suggest that treatment of early
pneumonia (i.e., prior to mechanical ventilation)
is associated with improved outcome.
| 330 | Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1)