Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children

Abstract

Summary:Adenovirus infection remains an important cause of mortality after bone marrow transplantation (BMT). Currently no efficient antiviral treatment is known. Thus, testing new modalities of early diagnosis and treatment is a crucial objective. Adenovirus infection is defined by the combination of symptoms and the isolation of virus from the source of clinical symptoms. The involvement of two or more organs and the presence of virus in blood cultures define disseminated disease. Seven children with a median age of 7 years received bone marrow transplantation for leukemia. All received an unrelated graft without T cell depletion. Adenovirus was sought in blood, urine and biopsy specimens using PCR and culture. Analysis of biopsy specimens included systematic immunohistochemistry. Cidofovir treatment was initiated as soon as biopsy revealed the histopathological signs of adenovirus. Cidofovir was given at 5 mg/kg once weekly for 3 weeks then every 2 weeks. Six patients had diarrhoea and one patient had cystitis. Adenovirus infection and disseminated disease were diagnosed in four cases and three cases, respectively. In six cases, serotype A31 was isolated from gastrointestinal biopsy and in two cases serotypes B2 and C6 were detected in blood and urine. Cidofovir treatment was associated with clinical improvement of diarrhoea, cystitis and fever in five patients, in whom the virus became undetectable in cultures and PCR analyses despite the persistence of immunodeficiency. The median follow-up was 360 days after BMT (240-570). One child died of invasive aspergillosis and another of disseminated adenovirus after interruption of cidofovir therapy. Further studies in immunocompromised patients will be needed to extend these promising results concerning the role of cidofovir in adenovirus infection. Bone Marrow Transplantation (2001) 27, 621-626.

Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin

“…We have already reported elsewhere in the treatment of PTLD these high-dose patients with donor lymphocyte infusions and anti-CD20 monoclonal antibodies, and the treatment of adenovirus infection with cidofovir. 11,14 Of the seven patients with adenovirus in the high-dose group, six received cidofovir, and five of them recovered from adenovirus infection. All three patients with PTLD in the high-dose group received anti-CD20 antibodies and/or donor lymphocyte infusions, and recovered from their PTLD.…”

Changes of serum growth factors (IGF-I,-II and IGFBP-2,-3) prior to and after stem cell transplantation in children with acute leukemia

“…Moreover, it is known that catabolic metabolism, liver dysfunction, acidosis, burning and systemic infections are associated with low IGF-I and IGFBP-3 serum concentration. [31][32][33][34][35] These possible influence factors should be considered in all interpretations. However, our measured IGF and IGFBP changes are much higher than the described changes in these conditions.…”

Adenovirus infection in children after allogeneic stem cell transplantation: diagnosis, treatment and immunity

“…[9][10][11] Failures and successes are reported for both drugs. A general conclusion from these studies was that rapid initiation of treatment after diagnosis of the infection is important.…”