High Incidence of Human Herpesvirus 6 Reactivation in Adult Recipients of Double Cord Blood Transplants

Vicky Kyriazi1, Eirini Grispou, Aikaterini Manaka, Constantine- George Balotis, Zoe Poulopoulou, Eirini Bika, Ioannis Baltadakis, Dimitri Karakasis, Mary Anagnostopoulou, Ioannis Apostolidis, Nicholas Harhalakis, Olga Paniara, Emmanuel NIikiforak

Author address: 

1BMT Unit Evaggelismos Hospital, Athens Greece; 2Microbiology Laboratory, Evaggelismos Hospital, Athens Greece


Introduction: Human herpesvirus 6 (HHV-6) reactivation may have significant consequences in cord blood transplant recipients (CBR). This study evaluates the incidence of HHV-6 reactivation, its manifestations and treatment in CBR at our center. Materials and Methods: From 8/2005 to 12/2007, 15 patients (pts), 25-61 years old, with high risk acute leukemias, underwent double cord blood transplantation. HHV-6 reactivation was noticed in 7 (47%) at a median time of 40 days (range 25-127) post-transplant. Myeloablative conditioning regimen was used in 5/7. Prophylactic antiviral therapy consisted of acyclovir (n=5/7) or foscarnet (n=2/7). Among them 2 pts had already CMV-infection and 6 (85.7%) suffered fromaGVHD and received methylprednisolone at the time of HHV-6 reactivation. Levels of HHV-6 DNA in PBMCs and plasma by RT-PCR were monitored every week. The viral load in PBMCs ranged from 0.02 to 5.1 x 104 copies/ml (median 0.41 x 104). Results: Clinical manifestations included fever, skin rash, thrombotic microangiopathy, seizures, bone and joint pain, hemophagocytosis, persistent thrombocytopenia, and several concurrent infections [bacterial (n=2): Pseudomonas putida, Staphylococcus epidermidis, Rhizobium radiobacter/fungal (n=2): Aspergillus, Acremonium/viral (n=4): CMV, EBV, BKV, RSV, Rhinovirus, Boca virus/parasitic (n=1): toxoplasma gondii. Despite the fact that the above manifestations could not always be attributed to HHV- 6, it seemed that their emergence and/or aggravation correlated with its reactivation. Engraftment with ANC>microliter and PLTs>50,000/microliter occurred at median time of 19 (range 6- 34) and 36 (range 41-95) days respectively. Two pts died before engraftment. Five pts received foscarnet and all but one responded at a median time of 10 days (range 9-19). The non-responder received cidofovir without response. In 3 pts, despite the reduction of viral load, viral DNA had been detected for several weeks. With a median follow up of 5 months (range 3-30), 3 pts died (systemic toxoplasmosis at d+52, leucoencephalopathy and sepsis at d+93, disease relapse at d+180). Conclusions: A high incidence of HHV-6 reactivation with a variety of manifestations was noticed, that may increase immunosuppression and predispose to infections, but no clear conclusion could be made about its impact on engraftment. Further investigation is needed to identify risk factors for HHV-6 reactivation, and optimal prophylactic therapy.

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Full conference title: 

15th International Symposium on Infections in the Immunocompromised Host
    • ISIIH 15th