Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

Abstract

The main risk factors for cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants (SCT) are recipient CMV seropositivity and acute graft-versus-host disease. Currently, two antiviral strategies, prophylactic or preemptive antiviral treatment, are used for prevention of CMV disease. Preemptive treatment is most favorable when short-term (14-day) treatment is applied. Several methods are available for monitoring of CMV reactivation. PCR-based CMV DNA detection assays are the most sensitive methods; however, the clinical benefit of this high sensitivity is unclear. Even more, there is lack of clarity whether PCR tests can better be performed with plasma, whole blood, or peripheral blood leukocyte samples. Recovery of a CMV-specific CD8+ cytotoxic-T-lymphocyte (CTL) response is necessary for preventing CMV reactivation and disease. Reconstitution of absolute CMV-specific CTL counts to values above 10 × 106 to 20 × 106 CTLs/liter is associated with protection from CMV disease. In the near future, preemptive therapy might be withheld in patients with CMV reactivation who are shown to have adequate CMV-specific cytotoxic T-cell levels. Antiviral therapy with (val)acyclovir has been studied only as prophylactic treatment for prevention of CMV infection. High-dose oral valacyclovir is more effective than acyclovir when used in addition to preemptive treatment of CMV reactivation with ganciclovir or foscarnet. Three antiviral drugs have been tested for preemptive therapy of CMV reactivation and/or treatment of CMV disease. Although intravenous ganciclovir is considered the drug of choice, foscarnet has similar efficacy and less toxicity, especially hematologic toxicity. Cidofovir has not been tested extensively, but so far the results are disappointing. Oral valganciclovir for preemptive treatment of SCT recipients is currently being studied. In addition to antiviral therapy, adoptive immunotherapy with CMV-specific cytotoxic T cells as prophylactic or preemptive therapy is a very elegant strategy; however, generation of these cells is expensive and time-consuming, and therefore the therapy is not available at every transplantation center. Magnetic selection of CMV-specific CD8+ T cells from peripheral blood by using HLA class I-peptide tetramers may be very promising, making this strategy more accessible

Acute renal failure after allogeneic myeloablative stem cell transplantation: retrospective analysis of incidence, risk factors and survival

“…In the first months after SCT, the major complications seen are sepsis (possibly leading to organ failure and admission to the intensive care unit (ICU)), 1 sinusoidal occlusion syndrome (SOS) (also known as veno-occlusive disease), 2 thrombotic thrombocytopenic purpura (TTP), 3 acute graft-versus-host disease (GVHD) 4 and cytomegalovirus (CMV) reactivation. 5 Several of these complications can be accompanied by acute renal failure (ARF), 2,3,[6][7][8][9] and are therefore risk factors for ARF. However, ARF can also occur in the absence of these complications, mainly as a result of nephrotoxic medications, such as amphotericin B 8 and cyclosporine.…”

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“…T-cell response recovery could be attributed not only to a reduction in the immuno suppressive therapy, but also, to the preemptive approach that is thought to allow an earlier reconstitution of cytomegalovirus responses compared with long-term prophylactic ganciclovir. 12 Instead, the responses to Aspergillus antigens were limited and only noticed late after the transplant, as reported in patients treated for hematologic malignancies. 4 In our report, the diagnosis of pulmonary aspergillosis was based on clinical and radiologic parameters along with the positivity of the respiratory cultures and plasma galactomannan.…”

Cytomegalovirus infection in non-immunosuppressed critically ill patients

“…Most of the studies involving these treatments have been performed in immunocompromised patients and transplant recipients [37,38,39]. There is a need to perform multicentre experimental studies using these antivirals in a large number of critically ill immunocompetent patients to come to a conclusion regarding their beneficial role in such cases.…”