Best Practice & Research Clinical Haematology
Vol. 20, No. 2, pp. 209e217, 2007
doi:10.1016/j.beha.2006.09.0035
Risk assessment in haematopoietic stem cell
transplantation: Viral status
Per Ljungman* MD, PhD
Professor, Head
Hematology Center, Karolinska University Hospital, Karolinska Institute, SE-14186 Stockholm, Sweden
Viral infections have been important complications in the transplant procedure from the early
days of stem-cell transplantation, causing significant morbidity and mortality. It is important
for the management of patients to assess the risk for viral infections that might develop after
the stem-cell transplantation. This can be exemplified by cytomegalovirus (CMV) and other
herpesviruses, but risk assessment is also important for other viral infections. The aim of this
review is to describe current knowledge regarding recipient and donor serological status for
viral infections.
Key words: viral infections; serology; CMV; stem-cell transplantation; donors.
Viral infections have been important complications in the transplant procedure from
the early days of stem-cell transplantation, causing significant morbidity and mortality.
Over the years, major improvements in the post-transplant management of viral
infections have been achieved. One of these achievements is the recognition that it
is of major importance to assess the patient’s risk for developing post-transplant viral
infections. For several viruses this risk assessment is made through pre-transplant
detection of the viral status of the patient and for several viruses also of the donor.
The aim of this review is to assess available evidence about when to perform pre-
transplant detection of viral markers, and the recommendations are made as
minimum-level recommendations.
DIAGNOSTIC TECHNIQUES
For many viruses, the use of serology to detect antibodies is the diagnostic technique
of choice. The presence of IgG antibodies against a virus indicates a previous infection
and, for some latent or persistent viruses, the possibility of post-transplant reactiva-
tion. IgM antibodies might indicate a recent infection, although false-positive reactions
* Tel.: þ46 8 58582507; Fax: þ46 8 7748725.
E-mail address: per.ljungman@ki.se
available online at http://www.sciencedirect.com1521-6926/$ - see front matter ª 2006 Elsevier Ltd. All rights reserved.

210 P. Ljungmanand cross-reactions do occur. However, serology is usually not useful for diagnosis of
active virus infections after SCT since many patients are unable to mount antibody
responses. For some viruses, techniques able to detect parts of the virus, such as
nucleic acids or viral antigens, are indicated. This applies for example for hepatitis B
virus and HIV, but might also be applicable in a situation where a recent primary
infection e for example with cytomegalovirus (CMV) e is suspected.
DONOR ISSUES
As a principle it can be stated that ongoing viral diseasee i.e. symptomatic infection for
examplewith respiratory syncytial virus (RSV), herpes simplex virus (HSV), or varicellae
zoster virus (VZV)e in the donor should be seen as a contraindication for donation. The
aims are both to eliminate the possible risks to the donor by performing the harvest
procedure during active infection and to reduce the risk of transfer of the virus to the
patient. The situation with asymptomatic viral infections in the donor is more difficult
and will be dealt with below under the respective viral pathogens.
CYTOMEGALOVIRUS
CMV-seronegative patients
The ideal situation is to have a CMV-seronegative patient and a CMV-seronegative
stem-cell donor since the risk for CMV disease in this combination is very low.1,2 In
seronegative patients with seropositive stem-cell donors (Dþ/R), primary CMV
infection develops in about 30%. Although the risk for CMV disease is low with
current preventive strategies, Nichols et al showed recently that there was an
increased mortality in bacterial and fungal infections in seronegative patients receiving
grafts from seropositive donors; this shows the importance of CMV as an immunosup-
pressive agent after allogeneic stem-cell transplantation, increasing the risk for both
bacterial and fungal infections after transplantation.3 Attempts should therefore
be made to find a CMV-seronegative donor for a CMV-seronegative patient. False-
negative results of serological testing do occur, and either the patient or the donor
can be in the incubation phase before antibodies can be detected. One question to
be considered is the case where only a seropositive sibling donor is available but there
might be a possibility of finding a CMV-seronegative unrelated donor. There is no avail-
able information regarding the relative risks comparing these two transplant options.
However, Nichols et al showed no impact on mortality by using a CMV-seropositive
donor for a CMV-seronegative patient receiving an HLA-identical sibling donor trans-
plant, whereas there was a significant impact in unrelated donor transplants.3 This
would suggest that a sibling donor is still the preferred alternative, even if the donor
is CMV-seropositive, compared to a CMV-negative unrelated donor for a CMV-
seronegative recipient. The situation might be different in a setting comparing a family
HLA-mismatched, CMV-mismatched donor with an unrelated CMV-matched donor,
but the data are lacking to make a recommendation.
CMV-seropositive patients
Reactivation of CMV occurs in approximately 80% of patients who are seropositive
before transplantation. Seropositivity of the patients still remains a risk factor for