212: Adenovirus (ADV) infections following allogeneic stem cell transplant (alloSCT) in children and adolescent recepients

Abstract

ADV is a serious cause of morbidity and mortality in patients undergoing alloSCT. ADV infection rates are 4-6% in adults and as high as 47% in children following alloSCT (Hoffman et al BBMT 2001). The reported mortality rate for disseminated ADV ranges from 8-54 % with higher rates reported in patients with ADV pneumonia (73%) and disseminated disease (61%) (Ljungman, Eur J Clin Microbiol & Infect Dis, 2004). We sought to determine the incidence, demographics, site of disease, treatment course, and outcome of ADV infection in children and adolescents following alloSCT from 1/1/2000-12/31/04. Eighty three children and adolescents underwent 91 alloSCT. Median age 6.5 (0.5 – 21.75) years, sex: M/F (52/39). AlloSCT donors included: Matched Family Donor (MFD), Bone Marrow (BM)/Peripheral Blood (PB) – 34 (37.4%), Unrelated Cord Blood(UCB) – 51 (56%), Related Cord Blood(RCB) - 3 (3.3%), Matched Unrelated Donor(MUD) – 3 (3.3%). Conditioning: 36 (40%) ablative conditioning, 55 (60%) reduced intensity conditioning. The majority (>90%) received Mycophenolate Mofetil/Tacrolimus GVHD prophylaxis (Osunkwo/Cairo et al, BBMT 2004). Recipients at risk for CMV received Foscarnet/Ganciclovir prophylaxis (Shereck/Cairo et al PBC 2006). ADV swabs and tissue biopsies samples cultured in remel microtest viral media. Ten (11%) systemic and/or invasive ADV infections were identified. Underlying diagnosis: 5 malignant (1ALL, 1 AML, 1 NHL, 2 NBL), 5 non-malignant (1WAS, 4 SAA). Donor source: 4 UCB, 1 MUD, 2 MFDPB, 1 MFDBM, 2 MFDBM + PB. Sites of ADV + culture: Gastroenteritis (GE) – 4, GE/Pneumonitis – 3, GE/Nasopharyngeal – 2, Cystits – 1. Treatment (Tx): cidofovir (CDV) (1mg/kg TIW) [n=8], observation [n=1], ADV found on post-mortem culture [n=1]. Outcome: 8 expired (6 non-ADV infection, 1 GVHD, 1 CNS hemorrhage); 2 survivors (1 post tx with no evidence of ADV, 1 ADV + no tx.) There were no ADV related deaths for 0% mortality. Adenovirus infection is an important contributor to post alloSCT morbidity and mortality. In patients transplanted at our center from 1/2000 –12/31/04 there was an 11 % incidence of adenovirus infection. Tx with CDV improves the outcome of patients with ADV infection in the post-transplant period. More rapid diagnosis with PCR-based technology will allow earlier diagnosis of systemic disease in alloSCT recipients resulting in prompt therapeutic intervention which may lead to improved outcomes. ADV is a serious cause of morbidity and mortality in patients undergoing alloSCT. ADV infection rates are 4-6% in adults and as high as 47% in children following alloSCT (Hoffman et al BBMT 2001). The reported mortality rate for disseminated ADV ranges from 8-54 % with higher rates reported in patients with ADV pneumonia (73%) and disseminated disease (61%) (Ljungman, Eur J Clin Microbiol & Infect Dis, 2004). We sought to determine the incidence, demographics, site of disease, treatment course, and outcome of ADV infection in children and adolescents following alloSCT from 1/1/2000-12/31/04. Eighty three children and adolescents underwent 91 alloSCT. Median age 6.5 (0.5 – 21.75) years, sex: M/F (52/39). AlloSCT donors included: Matched Family Donor (MFD), Bone Marrow (BM)/Peripheral Blood (PB) – 34 (37.4%), Unrelated Cord Blood(UCB) – 51 (56%), Related Cord Blood(RCB) - 3 (3.3%), Matched Unrelated Donor(MUD) – 3 (3.3%). Conditioning: 36 (40%) ablative conditioning, 55 (60%) reduced intensity conditioning. The majority (>90%) received Mycophenolate Mofetil/Tacrolimus GVHD prophylaxis (Osunkwo/Cairo et al, BBMT 2004). Recipients at risk for CMV received Foscarnet/Ganciclovir prophylaxis (Shereck/Cairo et al PBC 2006). ADV swabs and tissue biopsies samples cultured in remel microtest viral media. Ten (11%) systemic and/or invasive ADV infections were identified. Underlying diagnosis: 5 malignant (1ALL, 1 AML, 1 NHL, 2 NBL), 5 non-malignant (1WAS, 4 SAA). Donor source: 4 UCB, 1 MUD, 2 MFDPB, 1 MFDBM, 2 MFDBM + PB. Sites of ADV + culture: Gastroenteritis (GE) – 4, GE/Pneumonitis – 3, GE/Nasopharyngeal – 2, Cystits – 1. Treatment (Tx): cidofovir (CDV) (1mg/kg TIW) [n=8], observation [n=1], ADV found on post-mortem culture [n=1]. Outcome: 8 expired (6 non-ADV infection, 1 GVHD, 1 CNS hemorrhage); 2 survivors (1 post tx with no evidence of ADV, 1 ADV + no tx.) There were no ADV related deaths for 0% mortality. Adenovirus infection is an important contributor to post alloSCT morbidity and mortality. In patients transplanted at our center from 1/2000 –12/31/04 there was an 11 % incidence of adenovirus infection. Tx with CDV improves the outcome of patients with ADV infection in the post-transplant period. More rapid diagnosis with PCR-based technology will allow earlier diagnosis of systemic disease in alloSCT recipients resulting in prompt therapeutic intervention which may lead to improved outcomes.