How I treat adenovirus in hematopoietic stem cell transplant recipients

Abstract

Adenovirus (AdV) infections are very common in the general pediatric population. The delayed clearance in young persons imposes a threat to immunocompromised patients after hematopoietic stem cell transplantation (HSCT), who can reactivate the virus, resulting in life-threatening disseminated disease. Although a definitive cure requires adequate immune reconstitution, 2 approaches appear to be feasible and effective to improve the outcomes of AdV infections. Strict monitoring with AdV quantitative polymerase chain reaction followed by preemptive treatment with low-dose (1 mg/kg) cidofovir 3 times a week, is effective in most cases to bridge the severely immunocompromised period shortly after HSCT, with acceptable toxicity rates. For centers who have the access, AdV-specific cytotoxic T cells can be the other important cornerstone of anti-AdV therapy with promising results so far. Methods to positively influence the reconstitution of the immune system after HSCT and optimizing new and currently available cellular immunotherapies will make HSCT safer against the threat of AdV infection/reactivation and associated disease.

Figure 1

Adenoviral load in relation to T-cell numbers. A 2-year-old girl was treated with unrelated cord blood HSCT for Hurler syndrome (nonmalignant, MPS1). She developed an AdV primo infection or reactivation, which was detectable by AdV qPCR (100 cp/mL) at day 19. Within a period of 4 days the viral load increases by 2 log, and cidofovir is started. There are no signs of disease. Only as CD3 numbers (gray line) are increasing, adenoviral load (black line) goes down. The downward pointing arrow indicates the timing of intensification of therapy with immunosuppressants when the period after HSCT is complicated by steroid refractory autoimmune cytopenia; she receives mycophenolate mofetil 45 mg/kg/d, prednisone 2 mg/kg/d, anti-CD20 therapy, and fludarabine infusions from day 314. When symptoms stabilize, immunosuppressants are tapered over time and can be stopped at day 455 after HSCT. Tapering of immunosuppressants is associated with CD3⁺ T-cell recovery and clearance of advenoviremia.

Figure 2

How I treat AdV in HSCT recipients: treatment guideline. Refer to the text for a detailed explanation. Lympho. Prolif. Inh. Indicates lymphocyte proliferation inhibitor (eg, cyclosporin A, CsA); *alternative cidofovir 5 mg/kg intravenously weekly. **For centers that have the AdV CTLs readily available, CTLs are immediately initiated for all high-risk patients and for all patients with AdV symptoms before awaiting cidofovir effect.