Viral infections in pediatric bone marrow transplant patients

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252

Summary:We conducted a retrospective review of the clinical features and outcome of adenovirus infection in 572 consecutive patients transplanted in a single centre over a 10 year period. One hundred patients (17%) had a total of 105 episodes of adenovirus infection diagnosed at a median of 18 days post transplant (range 2-150 days). The incidence was higher in children than adults (21% vs 9%, P Ͻ 0.001) and in unrelated donor vs matched sibling donor transplants (26% vs 9%, P Ͻ 0.001). Diarrhoea and fever were the most common presenting features. Reflecting these symptoms, the most common site of isolation was the stool. Serotypes 1, 2 and 7 were the most frequently seen (total of 41/68 or 60% of evaluable cases). In six patients (6%) adenovirus infection was the direct cause of death occurring at a median of 72 days post transplant (range 18-365 days). Five of these six patients had pulmonary involvement and four had associated graft-versus-host disease (GVHD). Three further patients were considered to have severe adenoviral disease (total incidence 9%). Isolation of virus from multiple sites correlated with a poor outcome (P Ͻ 0.001). Comorbid viral infection was common in this group with 50% of all patients having other viruses isolated (predominantly polyoma virus and cytomegalovirus). We conclude that adenovirus is commonly isolated after bone marrow transplant and is a cause of significant morbidity but was a rare cause of mortality (6/572 = 1%) in our patient group as a whole. The relative infrequency of severe infection will make it difficult for the transplant physician to decide which patients should receive experimental antiviral drugs such as ribavirin and cidofovir or immunomodulatory therapy with donor white cell infusions. Bone Marrow Transplantation (2000) 26, 1333-1338. Keywords: adenovirus; bone marrow transplantation; diarrhoea; pneumonitis Viral infections are a common cause of morbidity and mortality after bone marrow transplantation. Severe, life-threat-

Section: Discussionmentioning

confidence: 99%

“…2 The serotypes are classified into six groups (A-F) on the basis of antigenic properties and DNA homology. Adenovirus is isolated in 5-21% of BMT patients [5][6][7] but its significance is often uncertain. It may be more common in children than adults.…”

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confidence: 99%

Outcome and clinical course of 100 patients with adenovirus infection following bone marrow transplantation

Baldwin¹,

Kingman²,

Darville

et al. 2000

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252

“…[1][2][3] Human herpes virus 6 (HHV6), which reactivates early after HSCT, was found to be associated with aGVHD and increased NRM in children and, recently, in adults. [4][5][6][7] Predictors for the development of HHV6 reactivation are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Human herpes virus 6 reactivation: important predictor for poor outcome after myeloablative, but not non-myeloablative allo-SCT

Pagter

Schuurman

Keukens

et al. 2013

Hematopoietic SCT (HSCT) is often complicated by viral reactivations. In this retrospective cohort study (January 2004-August 2008, predictors for human herpes virus 6 (HHV6)-reactivation and associations between HHV6-reactivation and clinical outcomes after allogeneic HSCT were studied. HHV6 DNA load in plasma was monitored weekly by quantitative real-time PCR. Associations between the main end point HHV6-reactivation and other end points, that is, acute GVHD (aGVHD) and NRM were analyzed using Cox proportional hazard models. In total, 108 patients receiving either a myeloablative (MA; n ¼ 60) or non-myeloablative (NMA; n ¼ 48) conditioning regimen were included. Median age was 40 years (range 17-65); median follow-up was 20 months (range 3-36). In 16/60 (27%) patients with MA conditioning regimen, a HHV6 reactivation was observed (mean viral load 50 323 cp/mL) compared with 2/48 (4%) patients with a NMA conditioning regimen with low viral load (mean 1100 cp/mL). In multivariate analysis, MA conditioning was the only predictor for HHV6 reactivation (P ¼ 0.02). In addition, HHV6 reactivation was associated with grades 2-4 aGVHD (Po0.001) and NRM (P ¼ 0.03). Regular monitoring of HHV6 reactivation after HSCT might be important in MA HSCT patients to enable early initiation of antiviral treatment or to anticipate aGVHD, all of which may improve clinical outcome. Herpes virus reactivations, like human CMV (HCMV) and EBV, have been described to be associated with aGVHD, allograft rejections and increased NRM. 1-3 Human herpes virus 6 (HHV6), which reactivates early after HSCT, was found to be associated with aGVHD and increased NRM in children and, recently, in adults. [4][5][6][7] Predictors for the development of HHV6 reactivation are largely unknown. To date, only broad-spectrum and relatively toxic antiherpes virus drugs (for example, (val)ganciclovir and foscarnet-sodium) are used in the treatment of HHV6 disease or -reactivation. 8,9 With the progress in molecular diagnostics, better monitoring allows for further elucidation of the role of HHV6 reactivation and therapeutic protocols after HSCT. Therefore, we studied the predictors for HHV6 reactivation and the association of HHV6 reactivation with clinical outcome in adult allogeneic-HSCT recipients.

“…In addition to the manifestations already described, adenovirus can cause hepatitis with or without hepatic necrosis, pancreatitis, nephritis and disseminated disease in immunodeficient hosts. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Consequently, mortality rates are high, ranging from 18 to 60%, with outcome dependent on patient age, type of immunosuppression, and adenovirus serotype. 3 Adenovirus infection in patients undergoing bone marrow transplantation, first described in 1985, can be severe with virus recoverable from many sites and often accompanied by significant morbidity and mortality.…”

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confidence: 99%

Adenovirus infection after pediatric bone marrow transplantation

Hale

Heslop

Krance

et al. 1999

241

209

Summary:Retrospective analysis of 206 patients undergoing 215 consecutive bone marrow transplants (BMT) at St Jude Children's Research Hospital between November 1990 and December 1994 identified 6% (seven male, six female) with adenovirus infection. The affected patients had a median age of 7.9 years (range 3-24 years) at time of transplantation. Although transplants were performed for hematologic malignancies, solid tumors or nonmalignant conditions, only patients with hematologic malignancies had adenoviral infections. Adenovirus was first detected at a median of 54 days (range ؊4 to ؉333) after BMT. Adenovirus developed in eight of 69 (11.6%) patients receiving grafts from matched unrelated or mismatched related donors, in four of 52 (7.7%) receiving grafts from HLA-matched siblings, and in one of 93 (1.1%) receiving autografts. The most common manifestation of adenovirus infection was hemorrhagic cystitis, followed by gastroenteritis, pneumonitis and liver failure. The incidence of adenovirus infection in pediatric BMT patients at our institution is similar to that reported in adult patients. Using univariate analysis, use of total body irradiation and type of bone marrow graft were significant risk factors for adenovirus infection. Only use of total body irradiation remained as a factor on multiple logistic regression analysis.