although adenovirus ( adv ) infection usually causes self - limiting respiratory disorders in immune competent children ; severe and systemic adv infection in children undergoing chemotherapy for leukemia has been continuously reported . nevertheless , there has been no consensus on risk factors and treatment strategies for severe adv infection in children undergoing chemotherapy . we report a case of a 15-year - old boy with a fatal systemic adv infection . he had received reinduction chemotherapy for relapsed acute lymphoblastic leukemia under continuing antifungal therapy for previously diagnosed fungal pneumonia . he complained of fever and right shoulder pain 4 days after completing the reinduction chemotherapy . in spite of appropriate antibiotic and antifungal therapy , a multiplex polymerase chain reaction test for respiratory viruses was positive for adv in a blood sample , and a urine culture was positive for adv . he received oral ribavirin , intravenous immunoglobulin , and intravenous cidofovir therapy ; however , he eventually died . relapsed leukemia , concurrent fungal pneumonia , and delayed cidofovir administration were considered the cause of the grave outcome in this patient . adv may cause severe infections not only in allogeneic hematopoietic cell transplant recipients , but also in patients undergoing chemotherapy for acute leukemia . the risk factors for severe adv infection in patients undergoing chemotherapy should be determined in the future studies , and early antiviral therapy should be administered to immune compromised patients with systemic adv infection . adenovirus ( adv ) infection usually causes self - limiting respiratory disorders in immune competent children . however , the severity of adv infection varies according to adv serotype , and higher severity and poorer prognosis have been observed in immune compromised children compared with immune competent children . among children receiving allogeneic hematopoietic cell transplantation ( hct ) , adv viremia occurred in 6% to 28% of cases , and 13% to 50% of patients with adv infection died . meanwhile , the incidence of adv infection is relatively low in children receiving anticancer chemotherapy for acute leukemia . adv reportedly causes less than 5% of respiratory viral infections in these patients , and few die from adv infections . we saw a case of fatal systemic adv infection in a child with acute lymphoblastic leukemia ( all ) . the patient received reinduction chemotherapy for relapsed all under antifungal therapy for previously diagnosed fungal pneumonia , and was infected by adv during neutropenia following the reinduction chemotherapy . although the patient did not receive allogeneic hct , relapsed all and concurrent fungal pneumonia in the patient might have led to the grave outcome of his adv infection . a 15-year - old boy complained of fever and right shoulder pain after reinduction chemotherapy for relapsed all . he was diagnosed with all at another hospital 3 years and 9 months prior , and was transferred to our hospital 2 months prior . at that time , he received reinduction chemotherapy for his second relapse of all ; however , there was no response , and he received another course of reinduction chemotherapy during this hospitalization . the patient had been diagnosed with possible invasive pulmonary aspergillosis ( ipa ) during a previous hospitalization and had received oral voriconazole ( 4  mg / kg twice a day ) therapy for 3 weeks following liposomal amphotericin b ( 5  mg / kg / day ) therapy for 2 weeks . on the fever day ( fd ) 1 , blood tests revealed a white blood cell count of 50/mm ( neutrophils 0% , lymphocytes 0% ) , hemoglobin concentration of 8.3  g / dl , platelet count of 53000/mm , erythrocyte sedimentation rate of 34 mm / h , c - reactive protein level of 8.70  mg / dl , and serum galactomannan level of 0.21 . chest x - ray images showed a round consolidation on the right upper lung fields , similar to the finding observed on admission ( fig . the dose of voriconazole was increased to 7  mg / kg twice daily because his serum voriconazole level was < 0.5  g / ml . empirical antibiotics were changed to meropenem and teicoplanin due to persisting fever on fd 3 . although his serum voriconazole level was 8.6  g / ml and serum galactomannan level was 0.14 on fd 6 , the fever persisted . chest computed tomography ( ct ) imaging performed on fd 6 showed an aggravation of the pneumonic consolidation on the right upper lobe compared with the chest ct images used for the diagnosis of fungal pneumonia during the previous hospitalization ( fig . the antifungal agent was changed to liposomal amphotericin b ( 5  mg / kg / day ) because we considered that the previously diagnosed possible ipa might actually be mucormycosis . however , his fever persisted , and gross hematuria developed on fd 12 . we suspected adv infection based on the concurrent hematuria and aggravation of the respiratory disease identified on the chest x - ray images ( fig . a multiplex polymerase chain reaction ( pcr ) test for respiratory viruses was positive for adv in a blood sample . the pcr test was qualitative with no report on viral dna titer , but the cycle threshold was 26.64 for positive pcr results . urinary bk virus , cytomegalovirus , and other bacteria were not identified ; however , a urine culture was later reported to be positive for adv . on fd 15 , oral ribavirin ( 10  mg / kg 3 times daily ) rather than cidofovir was initiated , as the patient had not received allogeneic hct and his general condition was relatively stable except for his prolonged fever . however , the fever and gross hematuria did not resolve , and chest x - ray images showed an aggravation of the pneumonia without respiratory symptoms . chest ct performed on fd 21 showed further aggravation of the pneumonic consolidation on the right upper lobe and a new consolidation on the right lower lobe accompanying pleural effusion ( fig . 2c ) . we considered superimposing adv pneumonia and proposed cidofovir therapy ; however , his parents did not accept this treatment due to its high costs . intravenous immunoglobulin ( ivig ) of 1  g / kg was administered for 3 days instead of cidofovir ; however , repeated multiplex pcr of blood was positive for adv , with a cycle threshold of 14.92 on fd 28 , and his fever persisted . although additional ivigs ( 150  mg / kg / day ) were administered for 5 days , the fever persisted , his serum creatinine level increased to 2.36  mg / dl and oliguria developed . on fd 33 , all antibiotic and antifungal agents were stopped due to acute kidney injury , and bilateral percutaneous nephrostomy was performed . his serum creatinine level began to decrease ; however , the fever did not resolve and chest x - ray images showed further aggravation of the pneumonia ( fig . although the first dose of cidofovir ( 5  mg / kg ) was administered on fd 36 , the patient complained of dyspnea and tachypnea , and required oxygen therapy on fd 38 . on fd 40 , multiplex pcr of a blood sample was again positive for adv , with a cycle threshold of 13.41 , and liposomal amphotericin b , which was stopped due to acute kidney injury , was readministered . mechanical ventilation was applied on fd 45 , and he died on fd 48 . a bronchial wash fluid culture from a sample collected on fd 46 was reported as positive for rhizopus spp . and adv after his death . chest x - ray images showing round consolidations on the right upper lung fields upon admission ( a ) , insignificant change in the consolidation on fever day 1 ( b ) , and aggravation of the pneumonic consolidation on fever days 12 ( c ) and 35 ( d ) , respectively . chest computed tomography showing pneumonic consolidation with surrounding ground glass opacity on the right upper lobe during the previous hospitalization ( a ) , and aggravation of the pneumonic consolidation on fever days 6 ( b ) and 21 ( c ) , respectively . weekly monitoring with quantitative pcr for adv in blood is recommended in allogeneic hct recipients at risk for adv infection , and preemptive antiviral therapy with cidofovir is recommended for patients positive for adv viremia . however , routine monitoring for adv infection in autologous hct recipients and leukemia patients receiving chemotherapy is not necessary due to its lower incidence and severity compared with allogeneic hct recipients . respiratory viral infections occur in 43% to 59% of children undergoing chemotherapy or those with febrile neutropenia ; however , severe complications due to respiratory viral infections are rare and mortality due to respiratory viral infections is only 0% to 2% . adv comprises only 2% to 5% of respiratory viral infections in immune compromised children , less frequent than rhinovirus and respiratory syncytial virus infections : thus , the clinical impact of adv infection has been underestimated . however , severe and systemic adv infection in children undergoing chemotherapy for leukemia has been continuously reported . children with severe adv infections tend to have low absolute lymphocyte counts ; however , severe adv infection may occur during any period of the scheduled chemotherapy , including induction , consolidation , and maintenance chemotherapy . nevertheless , there has been no report on risk factors for severe adv infection in children undergoing chemotherapy . future studies are required to elucidate the risk factors for severe adv infection in children undergoing chemotherapy , and appropriate strategies for early diagnosis and antiviral treatment for children most at risk should be established . although no specific antiviral therapy has been established for adv infection , cidofovir is recommended as the first - line agent for adv infection in allogeneic hct recipients . ribavirin is a broad - spectrum antiviral agent ; however , its antiviral mechanisms have not been exactly defined . because a significant efficacy of ribavirin was not observed in allogeneic hct recipients with systemic adv infections , it is not recommended as a therapeutic agent for adv infections in allogeneic hct recipients . however , its clinical effectiveness in allogeneic hct recipient with hemorrhagic cystitis due to adv has been reported . systemic adv infections , which occurred in a patient with myelodysplastic syndrome , who had not received hct , and in solid organ transplant recipients , responded to ribavirin therapy . our patient , who had not received allogeneic hct , was relatively clinically stable upon diagnosis of adv viremia , although he complained of fever and gross hematuria . at that time , we administered ribavirin rather than cidofovir because there are currently no guidelines for treatment of adv infection in children undergoing chemotherapy rather than hct . in addition , cidofovir may cause adverse effects , such as kidney injury and bone marrow suppression , and increase hospital cost . although cases showing the ivig effect on systemic adv infections in solid organ transplant recipients were reported , its effect on adv infections of immune compromised patients has not been evaluated in controlled studies . moreover therefore , ivig is not recommended as a therapeutic agent for adv infections as well as ribavirin . although our patient 's clinical status and viremia worsened after ribavirin therapy , cidofovir therapy was delayed for 3 weeks after the diagnosis of adv viremia due to parental hesitation in deciding to administer cidofovir . despite administration of cidofovir , 43% to 50% of allogeneic hct recipients with adv viremia die : early administration of cidofovir reportedly improves the prognosis of adv infections . although our patient had not received allogeneic hct and t - cell - specific immune suppressants , uncontrolled underlying all , concurrent fungal pneumonia , and delayed cidofovir administration could have led to the grave outcome . fatal adv infections in allogeneic hct recipients with concurrent bacterial and fungal coinfections have been reported , although the adv dna titers from blood samples were low . in conclusion , adv may cause severe infections not only in allogeneic hct recipients , but also in patients undergoing chemotherapy for acute leukemia . adv infection should be considered in immune compromised patients with severe respiratory tract infections or hemorrhagic cystitis . the risk factors for severe adv infection in patients undergoing chemotherapy should be determined , and early antiviral therapy should be administered to immune compromised patients with systemic adv infection .
abstractbackground : although adenovirus ( adv ) infection usually causes self - limiting respiratory disorders in immune competent children ; severe and systemic adv infection in children undergoing chemotherapy for leukemia has been continuously reported . 
 nevertheless , there has been no consensus on risk factors and treatment strategies for severe adv infection in children undergoing chemotherapy.case summary : we report a case of a 15-year - old boy with a fatal systemic adv infection . 
 he had received reinduction chemotherapy for relapsed acute lymphoblastic leukemia under continuing antifungal therapy for previously diagnosed fungal pneumonia . 
 he complained of fever and right shoulder pain 4 days after completing the reinduction chemotherapy . in spite of appropriate antibiotic and antifungal therapy , 
 pneumonia was aggravated and gross hematuria was accompanied . 
 a multiplex polymerase chain reaction test for respiratory viruses was positive for adv in a blood sample , and a urine culture was positive for adv . 
 he received oral ribavirin , intravenous immunoglobulin , and intravenous cidofovir therapy ; however , he eventually died 
 . relapsed leukemia , concurrent fungal pneumonia , and delayed cidofovir administration were considered the cause of the grave outcome in this patient.conclusion:adv may cause severe infections not only in allogeneic hematopoietic cell transplant recipients , but also in patients undergoing chemotherapy for acute leukemia . 
 the risk factors for severe adv infection in patients undergoing chemotherapy should be determined in the future studies , and early antiviral therapy should be administered to immune compromised patients with systemic adv infection .