Cytomegalovirus in Hematopoietic Stem Cell Transplant Recipients

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Diagnostic methods

The serologic determination of CMV-specific antibodies (IgG and IgM) is important for determining a patient's risk for CMV infection after transplantation but cannot be used for the diagnosis of CMV infection or disease. Growth of CMV in tissue culture takes several weeks, making this technique obsolete for diagnosis of CMV in HSCT recipients. The shell vial (rapid culture/DEAFF) technique, in which monoclonal antibodies are used to detect CMV immediate-early proteins in cultured cells, is not

Clinical manifestations

CMV infection is defined as the detection of CMV, typically by DNA PCR, pp65 antigenemia, or mRNA nucleic acid sequence-based amplification, from plasma or whole blood in a CMV-seronegative patient (primary infection) or a CMV-seropositive patient (reactivation of latent or persistent virus or superinfection with another strain of CMV).50, 51 International definitions of CMV disease, requiring the presence of symptoms and signs compatible with CMV end-organ involvement together with the

Allogeneic HSCT Recipients

In allogeneic HSCT recipients, the most important risk factors for CMV disease are the serologic status of the donor and recipient. CMV-seronegative patients receiving stem cells from a CMV-seronegative donor (D-/R-) have a very low risk of primary infection if CMV-safe blood products are used. Approximately 30% of seronegative recipients transplanted from a seropositive donor (D+/R-) develop primary CMV infection. Although the risk of CMV disease is low because of preemptive treatment of CMV

Prevention of CMV infection and disease

CMV serology should be assessed as early as possible when a patient is considered a candidate for HSCT and safe blood products should be used in CMV-seronegative candidates to reduce the risk for primary CMV infection. To reduce the risk for transmission of CMV, blood products from CMV-seronegative donors or leukocyte-reduced, filtered blood products should be used.110, 111, 112 Recipients who are CMV seronegative before allogeneic HSCT should ideally receive a graft from a CMV-negative donor.

Antiviral resistance

Risk factors for drug resistance include prolonged (months) antiviral therapy, intermittent low-level viral replication in the presence of drug caused by profound immunosuppression or suboptimal drug levels, and lack of prior immunity to CMV.143 Drug resistance should be suspected in patients who have increasing quantitative viral loads for more than 2 weeks despite antiviral therapy. After start of antiviral therapy in treatment-naive patients, an increase in the viral load occurs in

Management of CMV disease

Several studies established the current standard of care for CMV pneumonia, which is treatment with ganciclovir (or foscarnet as an alternative agent) in combination with IVIG.152, 153, 154, 155 These studies showed improved survival rates compared with historical controls. There does not seem to be a specific advantage of CMV-specific immunoglobulin (CMV-Ig) compared with pooled immunoglobulin.153 In specific clinical situations, however, such as volume overload, CMV-Ig may be preferred.

Adoptive immunotherapy

CMV-specific T cells can be generated by several different mechanisms to restore cellular immunity passively after transplantation.5 Several groups have reported a beneficial impact of adoptive immunotherapy on CMV viral loads in patients who had undergone HSCT.164 Despite these seemingly promising results, scientific questions remain unanswered (eg, the optimal cell type and dose for infusion) and technical hurdles persist (availability of clinical grade reagents) that preclude adoptive

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    Per Ljungman had support from the Karolinska Institute research funds, the European Leukemia Net, and the Swedish Children's Cancer Fund. Michael Boeckh had support from the National Institute of Health (NIH CA 18029).

    A version of this article was previously published in the Infectious Disease Clinics of North America, 24:2.

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