Cidofovir for Adenovirus Infection after Allogenic Hematopoietic Stem Cell Transplantation: A Single-Center Experience of 16 Childrens.

Adenovirus is an important cause of morbidity and mortality in pediatric hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis of 16 patients treated with cidofovir as first-line therapy for adenovirus, from one center. Transplants were performed for primary immunodeficiencies (n=9), other inherited diseases (n=5), acute leukemia (n=1) and Langerhans cell histiocytosis (n=1). Six patients received HSCT from matched sibling donor, 6 from unrelated donor and 4 from a family haploidentical donor. Bone marrow was T-cell depleted in 5 transplants. Nine patients received ATG or Campath as GVHD prophylaxis. Eight patients had a acute GVHD of grade II to IV and 4 received Campath as GVH treatment. Four patients had chronic GVHD. Adenovirus subgenus were A for 10 patients, C for 5 patients and one patient had a coinfection with A and C adenovirus. Symptoms were fever (n=11), diarrhae (n=14), pneumonitis (n=4), hepatitis (n=6) and hematuria (n=1).Eight patient had a viral co-infection. Real-time quantitative PCR was used for detection and monitoring of adenovirus. The median time of first detection was day+7 after HSCT. Four patients had a first detection before HSCT and for 3 of them cidofovir was started before HSCT. All the patients had adenovirus detected from blood with a median time of day+19 afterHSCT. The median number of positive sites before HSCT was 3. Cidofovir was started at a median of 28 days after HSCT. Dosage per infusion was 5mg/kg for 8 patients and 3mg/kg for 4 patients. Four patients received 3 or 5mg/kg.A median number of four infusion was given during a median of 32 days. Median follow-up was 13 months.

Of the 16 children, 14 were successfully treated with cidofovir and two failed therapy and died from disseminated adenovirus disease. One patient died from GVHD. In total, 6 patients had no toxicity, 5 developed a reversible tubulopathy. Of note, 3 children improved under treatment suggestinfg a possible nephritis induced by adenovirus. The discontinuation of the drug was not required in any patient. We conclude that cidofovir may be efficient for adenovirus infection after HSCT in pediatric patients but prospective controlled trials are warranted.