PURPOSE:Dexrazoxane has been used as an effective cardioprotector against anthracycline cardiotoxicity. This study intended to analyze cardioprotective efficacy and secondary malignancy development, and elucidate risk factors for secondary malignancies in dexrazoxane-treated pediatric patients.MATERIALS AND METHODS:Data was collected from 15 hospitals in Korea. Patients who received any anthracyclines, and completed treatment without stem cell transplantation were included. For efficacy evaluation, the incidence of cardiac events and cardiac event-free survival rates were compared. Data about risk factors of secondary malignancies were collected.RESULTS:Data of total 1,453 cases were analyzed; dexrazoxane with every anthracyclines group (D group, 1,035 patients) and no dexrazoxane group (non-D group, 418 patients). Incidence of the reported cardiac events was not statistically different between two groups; however, the cardiac event-free survival rate of patients with more than 400 mg/m2 of anthracyclines was significantly higher in D group (91.2% vs. 80.1%, p=0.04). The 6-year cumulative incidence of secondary malignancy was not different between both groups after considering follow-up duration difference (non-D, 0.52%±0.37%; D, 0.60%±0.28%; p=0.55). The most influential risk factor for secondary malignancy was the duration of anthracycline administration according to multivariate analysis.CONCLUSION:Dexrazoxane had an efficacy in lowering cardiac event-free survival rates in patients with higher cumulative anthracyclines. As a result of multivariate analysis for assessing risk factors of secondary malignancy, the occurrence of secondary malignancy was not related to dexrazoxane administration.

BACKGROUND:Autoimmune cytopenia (AIC) is a rare complication of allogeneic hematopoietic cell transplantation (HCT). In this study, we reviewed the diagnosis, treatment and response to therapy for pediatric patients with post-HCT AIC at our institution.METHODS:Of the 292 allogeneic HCTs performed from January, 2011 to December, 2015 at the Department of Pediatrics, The Catholic University of Korea, seven were complicated by post-HCT AIC, resulting in an incidence of 2.4%.RESULTS:All seven patients with post-HCT AIC had received unrelated donor transplant. Six of seven patients had a major donor-recipient blood type mismatch. The subtypes of AIC were as follows: immune thrombocytopenia (ITP) 2, autoimmune hemolytic anemia (AIHA) 2, Evans syndrome 3. Median time from HCT to AIC diagnosis was 3.6 months. All but one patient responded to first line therapy of steroid±intravenous immunoglobulin (IVIG), but none achieved complete response (CR) with this treatment. After a median duration of treatment of 15.3 months, two patients with ITP achieved CR and five had partial response (PR) of AIC. Five patients were treated with rituximab, resulting in the following response: 2 CR, 2 PR, 1 no response (NR). Median time to response to rituximab was 26 days from first infusion. All patients are alive without event.CONCLUSION:Post-HCT AIC is a rare complication that may not resolve despite prolonged therapy. Rapid initiation of second line agents including but not limited to B cell depleting treatment should be considered for those that fail to achieve CR with first line therapy.

BACKGROUND:Although intravenous acyclovir therapy is recommended for varicella zoster virus (VZV) infection in immunocompromised children, the clinical characteristics and outcomes of VZV infection in the acyclovir era have rarely been reported.METHODS:The medical records of children diagnosed with varicella or herpes zoster virus, who had underlying hematologic malignancies, were retrospectively reviewed, and the clinical characteristics and outcomes of VZV infection were evaluated.RESULTS:Seventy-six episodes of VZV infection (herpes zoster in 57 and varicella in 19) were identified in 73 children. The median age of children with VZV infection was 11 years (range, 1-17), and 35 (46.1%) episodes occurred in boys. Acute lymphoblastic leukemia was the most common underlying malignancy (57.9%), and 90.8% of the episodes occurred during complete remission of the underlying malignancy. Acyclovir was administered for a median of 10 days (range, 4-97). Severe VZV infection occurred in 16 (21.1%) episodes. Although the finding was not statistically significant, a previous history of hematopoietic cell transplantation (HCT) appeared to be associated with the development of more severe episodes of herpes zoster (P=0.075).CONCLUSION:Clinical characteristics of VZV infection in immunocompromised children were not significantly different from those without it, and clinical outcomes improved after the introduction of acyclovir therapy. However, risk factors for severe VZV infection require further investigation in a larger population and a prospective setting.

Background: Recent studies indicate 70-80% event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL). In this study, we report the outcome of 295 children and adolescents treated at our institution, with stratification into four risk groups, and omission of cranial irradiation in all patients.Procedure: Patients were diagnosed from January 2005 to December 2011 and classified and treated as low, standard, high, and very high risk groups. A delayed intensification phase was given twice for high and very high risk groups. None of the patients received cranial irradiation for central nervous system (CNS) prophylaxis.Results: The 10-year EFS and overall survival (OS) were 78.5 +/- 2.5% and 81.9 +/- 2.7%, respectively. EFS according to risk group was as follows: low risk 91.2 +/- 3.7%, standard risk 98.1 +/-+/- 1.9%, high risk 81.5 +/- 4.3%, very high risk 59.4 +/- 5.3%. In a multivariate analysis, high hyperdiploidy and infant ALL were significant predictors of EFS. Cumulative incidence of any relapse, isolated CNS relapse, and any CNS relapse were 17.1 +/- 2.3%, 1.5 +/- 0.7%, and 2.3 +/- 0.9%, respectively. Other events included infection-related deaths during remission induction chemotherapy (3), primary refractory disease (2), and treatment-related deaths in first complete remission (8).Conclusions: In this single-institution study of Korean pediatric ALL patients, risk group based intensification with omission of cranial irradiation resulted in EFS comparable to previous studies, excellent survival of low-and standard-risk patients, and a low rate of CNS relapse.

Purpose Severe aplastic anemia (SAA), a fatal disease, requires multiple transfusion, immunosuppressive therapy, and finally, hematopoietic stem cell transplantation (HSCT) as the definitive treatment. We hypothesized that iron overloading associated with multiple transfusions and HSCTrelated complications may adversely affect cardiac function. Left ventricular (LV) function was assessed in children after HSCT for SAA. Methods Forty-six consecutive patients with a median age of 9.8 years (range, 1.5-18 years), who received HSCT for SAA and who underwent comprehensive echocardiography before and after HSCT, were included in this study. The data of LV functional parameters obtained using conventional echocardiography, tissue Doppler imaging (TDI), and speckle-tracking echocardiography (STE) were collected from pre- and post-HSCT echocardiography. These data were compared to those of 40 age-matched normal controls. Results In patients, the LV ejection fraction, shortening fraction, end-diastolic dimension, mitral early diastolic E velocity, TDI mitral septal E' velocity, and STE LV longitudinal systolic strain rate (SSR) decreased significantly after HSCT. Compared to normal controls, patients had significantly lower post-HSCT early diastolic E velocity and E/A ratio. On STE, patients had significantly decreased LV deformational parameters including LV longitudinal systolic strain (SS), SSR, and diastolic SR (DSR), and circumferential SS and DSR. Serum ferritin levels showed weak but significant correlations (P<0.05) with LV longitudinal SS and SSR and circumferential SS and DSR. Conclusion Subclinical LV dysfunction is evident in patients after HSCT for SAA, and was associated with increased iron load. Serial monitoring of cardiac function is mandatory in this population.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for severe aplastic anemia (SAA); however, the optimal conditioning regimen for HSCT with an unrelated donor has not yet been defined. A previous study using a fludarabine (FLU), cyclophosphamide (Cy), and antithymocyte globulin (ATG) conditioning regimen (study A: 50 mg/kg Cy once daily i.v. on days -9, -8, -7, and -6; 30 mg/m(2) FLU once daily i.v. on days -5, -4, -3, and -2; and 2.5 mg/kg of ATG once daily i.v. on days -3, -2, and -1) demonstrated successful engraftment (100%) but had a high treatment-related mortality rate (32.1%). Therefore, given that Cy is more toxic than FLU, we performed a new phase II prospective study with a reduced-toxicity regimen (study B: 60 mg/kg Cy once daily i.v. on days -8 and -7; 40 mg/m(2) FLU once daily i.v. on days -6, -5, -4, -3, and -2; and 2.5 mg/kg ATG once daily i.v. on 3 days). Fifty-seven patients were enrolled in studies A (n = 28) and B (n = 29), and donor type hematologic recovery was achieved in all patients in both studies. The overall survival (OS) and event-free survival (EFS) rates of patients in study B was markedly improved compared with those in study A (OS: 96.7% versus 67.9%, respectively, P = .004; EFS: 93.3% versus 64.3%, respectively, P = .008). These data show that a reduced-toxicity conditioning regimen with FLU, Cy, and ATG may be an optimal regimen for SAA patients receiving unrelated donor HSCT.

PURPOSE:ETV6/RUNX1 (+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables.MATERIALS AND METHODS:Sixty-three patients were diagnosed with ETV6/RUNX1 (+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETV6/RUNX1 (+) fusion, and the presence of additional cytogenetic abnormalities.RESULTS:The 5-year event-free survival was 84.1±4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9±4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative-polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5±6.9%.CONCLUSION:ETV6/RUNX1 (+) ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end ofremission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.

Abdominal pain may precede the characteristic varicella skin lesions in immunocompromised patients with visceral varicella. The absence of skin lesions may delay timely diagnosis and treatment of varicella for those patients. Furthermore, abdominal imaging findings to provide information to diagnose visceral varicella have rarely been reported. Varicella was diagnosed in a 5-year-old boy with acute lymphoblastic leukemia complaining of fever and abdominal pain followed by papulovesicular skin lesions. Later, the patient was found to have rapidly progressive acute hepatitis, and abdominal computed tomography showed multiple hypodense hepatic nodules. The patient was treated with intravenous acyclovir, intravenous immunoglobulin, and empirical antibiotic and antifungal therapy. However, his fever and abdominal pain persisted, and a laparoscopic liver biopsy was performed to differentiate other causes of the persisting symptoms. Eventually, the patient was diagnosed with visceral varicella based on histopathologic findings. In conclusion, visceral varicella should be considered in immunocompromised patients with abdominal pain and multiple hypodense hepatic nodules on abdominal imaging studies. However, bacteria, fungi, and tuberculosis can produce similar imaging findings; therefore, a biopsy may be necessary in patients not responding to antiviral therapy.

Although cytomegalovirus (CMV) retinitis is usually diagnosed in allogeneic hematopoietic cell transplantation recipients among patients with hematologic and oncologic disease, it can also occur in acute leukemia patients who have not received hematopoietic cell transplantation. However, CMV retinitis diagnosed after completion of chemotherapy for acute leukemia has not previously been reported. A 17-year-old boy was diagnosed with CMV retinitis 3 months after completion of chemotherapy for acute lymphoblastic leukemia, and his retinitis was assumed to be caused by a delayed immune reconstitution after chemotherapy. The patient was treated with intravenous and intravitreous ganciclovir therapy, and subsequently underwent surgery for retinal detachment.

Invasive pulmonary aspergillosis (IPA) is the most frequent form of invasive fungal diseases in immunocompromised patients. However, there are only a few studies on IPA in immunocompromised children in Korea. This study was designed to characterize IPA in Korean children with hematologic/oncologic diseases. Medical records of children with hematologic/oncologic diseases receiving antifungal therapy were reviewed. The enrolled children were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups. During the study period, 265 courses of antifungal therapy were administered to 166 children. Among them, two (0.8%) episodes of proven IPA, 35 (13.2%) of probable IPA, and 52 (19.6%) of possible IPA were diagnosed. More children in the IPA group suffered from neutropenia lasting for more than two weeks (51.4% vs. 21.9%, P < 0.001) and showed halo signs on the chest computed tomography (78.4% vs. 40.7%, P < 0.001) than in the non-IPA group. No other clinical factors showed significant differences between the two groups. Amphotericin B deoxycholate was administered as a first line antifungal agent in 33 (89.2%) IPA group episodes, and eventually voriconazole was administered in 27 (73.0%) episodes. Ten (27.0%) children in the IPA group died within 12 weeks of antifungal therapy. In conclusion, early use of chest computed tomography to identify halo signs in immunocompromised children who are expected to have prolonged neutropenia can be helpful for early diagnosis of IPA and improving prognosis of children with IPA.

Background Invasive pulmonary aspergillosis (IPA) is the most common invasive fungal disease in immunocompromised patients, and it has a 30 % mortality rate despite appropriate antifungal therapy. This retrospective study was performed to determine risk factors for mortality in immunocompromised children with IPA. Methods Medical records of 45 probable/proven IPA cases diagnosed in children with hematologic/oncologic diseases were reviewed. Selected cases were divided into the survival ( n = 30) and fatality ( n = 15) groups based on survival at 12 weeks after antifungal therapy. Clinical characteristics and serum galactomannan indices (GMIs) were compared between the two groups. Results Significantly more children in the fatality group were male ( p = 0.044), not in complete remission of the underlying malignancies ( p = 0.016), and had received re-induction/salvage or palliative chemotherapy ( p = 0.035) than those in the survival group. However, none of these factors was significantly associated with mortality in a multivariate analysis. Serum GMIs were higher in the fatality group than in the survival group during the entire period of antifungal therapy, and serum GMI at 1 week after antifungal therapy was most significantly associated with mortality. A serum GMI > 1.50 at 1 week after antifungal therapy exhibited a sensitivity and specificity of 61.5 % and 89.3 %, respectively, in predicting mortality within 12 weeks after antifungal therapy. Conclusions Higher serum GMI in the early phase of antifungal therapy was associated with mortality in immunocompromised children with IPA. These children should receive more intensive care for IPA than others.

Invasive Pulmonary Aspergillosis after Recent Influenza in a Child with Acute Myeloid Leukemia Beom-Joon Kim, M.D., Seong koo Kim, M.D., Seung Beom Han, M.D., Jae Wook Lee, M.D., Ph.D., Jong-Seo Yoon, M.D., Ph.D., Nack-Gyun Chung, M.D., Ph.D., Bin Cho, M.D., Ph.D., Jin Han Kang, M.D., Ph.D. and Hack-Ki Kim, M.D., Ph.D. Department of Pediatrics, The Catholic Blood and Marrow Transplantation Center, The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea

To gain insight into the natural history of cytomegalovirus (CMV) infection following unrelated cord blood transplantation (UCBT) in seropositive patients, we analyzed the data of 349 seropositive patients who received UCBT in Korea between 2000 and 2011. CMV reactivation occurred in 49 % (171/349) of the CMV-seropositive transplant recipients at a median of 31 days post UCBT. One hundred sixty-four out of 171 patients (96 %) received preemptive therapy. The median duration of CMV reactivation was 29 days. In multivariate analysis, weight >22 kg, use of total body irradiation, use of pre-transplant antithymocyte globulin, graft-versus-host disease (GVHD) prophylaxis with mycophenolate mofetil, and presence of grade II–IV acute GVHD were independent predictors of CMV reactivation. CMV reactivation did not impact transplantation-related mortality (TRM), leukemia relapse, or survival. CMV disease was diagnosed in 62 patients (17.8 %) at a median 55 days after UCBT. Longer duration of CMV reactivation was the only risk factor for progression to CMV disease (p = 0.01). CMV disease resulted in higher TRM (56.0 vs. 31.4 %, p < 0.01) and lower survival (36.1 vs. 55.1 %, p = 0.02).

Background and Objectives: Cardiovascular complications are the leading cause of morbidity and mortality in childhood cancer survivors. Hematopoietic stem cell transplantation (HSCT) is a curable therapy for pediatric cancer. However, changes in cardiac function in children after HSCT are not well known. We assessed left ventricular (LV) function in children after HSCT using speckle tracking echocardiography (STE).Subjects and Methods: Forty consecutive patients with median age of 11.9 years (range, 1.5-16 years) who received HSCT for acute leukemia and had comprehensive echocardiography before and after (median 9.2 month) HSCT were included in this study. The LV function parameters including conventional tissue Doppler imaging (TDI) and STE data were collected from pre-and post-HSCT echocardiography. These data were compared to those of 39 age-matched normal controls.Results: Compared to normal controls, post HSCT patients had similar (p=0.06) LV ejection fraction. However, the following three LV function parameters were significantly decreased in post HSCT patients: rate-corrected velocity of circumferential fiber shortening (p=0.04), mitral inflow E velocity (p<0.001), and mitral septal annular E' velocity (p=0.03). The following four STE parameters were also significantly decreased in post HSCT patients: LV global circumferential systolic strain (p<0.01), strain rate (SR, p=0.01), circumferential diastolic SR (p<0.01), and longitudinal diastolic SR (p<0.001). There was no significant change in TDI or STE parameters after HSCT compared to preHSCT. Patients with anthracycline cumulative dose >400 mg/m(2) showed significantly (p<0.05) lower circumferential systolic strain and circumferential diastolic SR.Conclusion: Subclinical cardiac dysfunction is evident in children after HSCT. It might be associated with pre-HSCT anthracycline exposure with little effect of conditioning regimens. Serial monitoring of cardiac function is mandatory for all children following HSCT.

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO−), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO+). The 5-year overall survival (OS) rates in the SS, MS-RO−, and MS-RO+ groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ⩽2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO+ patients and reduce reactivation in younger patients with MS involvement.

Duration of acyclovir prophylaxis, mean±SD, weeks 8.9±2.2 10.5±4.4 0.003 Relapse of underlying malignancy after HCT 10 (30.3) 55 (29.9) 0.962 Epstein-Barr virus reactivation 28 (84.8) 141 (76.6) 0.295 Cytomegalovirus reactivation 20 (60.6) 96 (52.2) 0.371 Acute graft-versus-host disease (≥ Grade II) 12 (36.4) 68 (37.0) 0.948 Chronic graft-versus-host disease 9 (27.3) 63 (34.2) 0.434 Overall death* 5 (17.2) 46 (26.0) 0.312

Background: Neutropenia is not uncommon in children. We performed this study to in- vestigate the etiology, clinical course and laboratory characteristics for prediction of re- covery in children with severe neutropenia. Methods: In this study, we studied the clinical course and hematological features of 107 patients with severe neutropenia who were diagnosed and treated at the Department of Pediatrics, The Catholic University of Korea from April 2009 to July 2014. Patients with hematologic disorders and malignant disease were excluded. Chronic severe neu- tropenia (CSN) was defined as an absolute neutrophil count of 0.5×10 9 /L or less for at least 3 months. Acute severe neutropenia (ASN) were defined who recovered within 3 months from diagnosis. Results: Among 107 patients, 72 patients showed ASN and 35 patients were CSN. Median age of ASN (15.2 months) was higher than that of CSN (10.7 months). The median dura- tion of recovery from neutropenia was 7 days (range: 2-35) in ASN. ASN was commonly related to infectious diseases and 24 cases (33.3%) had documented etiologic agents. Median duration of recovery from neutropenia was 18 months in CSN. Three of 35 pa- tients in CSN had ELANE gene mutation. The number of white blood cells, platelets, monocytes, and eosinophils were significantly higher in group of CSN compared with ASN (P<0.05). Conclusion: We confirmed the great etiological heterogeneity of severe neutropenia in this study. The kinetics of recovery from neutropenia was different between the ASN and CSN group and the complete blood counts may be useful indices for discriminating ASN from CSN.

The present study was conducted to investigate Epstein-Barr virus (EBV) reactivation after hematopoietic cell transplantation (HCT) in Korean children living in an area of a high seroprevalence against EBV and to determine the impact of recipient age on EBV reactivation. Medical records of 248 children and adolescents who had received allogeneic HCT were retrospectively reviewed. The trends of EBV reactivation and post-transplant lymphoproliferative disorders (PTLDs) were evaluated and compared between younger (≤10 years old) and older (11–20 years old) groups. EBV reactivation occurred in 177 cases (71.4 %) and high-level EBV reactivation, defined as a virus DNA titer of 300,000 copies/mL or higher, occurred in 21 cases (8.5 %). PTLD was diagnosed in five cases (2.0 %), and one of these patients died. The EBV reactivation rate was not significantly different between the two age groups; however, high-level reactivation and PTLD were more significantly frequent in the older than in the younger group (P = 0.030 and P = 0.026, respectively). In conclusion, older children and adolescents are more likely to experience high-level EBV reactivation and PTLDs, and higher EBV DNA titers than those previously reported may be a predictor of PTLD in areas with a high seroprevalence against EBV.

Varicella-zoster virus infection can lead to severe illness in immunocompromised patients. Further the mortality rate of disseminated varicella infection is extremely high particularly in immunocompromised children. We report a case of disseminated varicella infection in a child with acute lymphoblastic leukemia who was receiving chemotherapy, but was initially admitted with only for acute abdominal pain. The patient rapidly developed severe complications, including acute respiratory distress syndrome, acute hepatitis, disseminated intravascular coagulation, and encephalopathy. Acyclovir is a highly potent inhibitor of varicella-zoster virus infection. However, owing to rapid disease progression, it might not be sufficient to control a disseminated varicella infection, especially in immunocompromised patients. Immunoglobulin neutralize virus invasion and suppress viremia, acting synergistically with acyclovir. In this case, early administration of acyclovir and a high-dose of immunoglobulin, combined with mechanical respiratory support, proved adequate for treatment of this severe illness.

This retrospective study was conducted to evaluate clinical outcomes of bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and their antibiotic susceptibilities in febrile neutropenic children. Clinical characteristics, prognosis, and antibiotic susceptibilities were reviewed and compared between febrile neutropenic children with bacteremia caused by ESBL-producing and non-ESBL-producing E. coli and K. pneumoniae. A total of 61 episodes of E. coli and K. pneumoniae bacteremia, including 21 episodes (34.4%) due to ESBL-producing strains, were diagnosed. There was no significant factor associated with bacteremia by ESBL-producing strains. Empirical antibiotics were appropriate in 85.7% of the ESBL group and 95.0% of the non-ESBL group. In the entire study population, seven deaths (11.5%), including three deaths (4.9%) due to E. coli and K. pneumoniae bacteremia, occurred. The complication and mortality rates were not significantly different between the two groups. Antibiotic susceptibility rates were significantly lower in the ESBL group than in the non-ESBL group in most antibiotics. Although 52.4% and 66.7% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam and cefepime, respectively, 96.7% of all the isolates and 90.5% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam or cefepime in combination with aminoglycoside. In conclusion, the ESBL group did not show a significantly unfavorable outcome, and empirical therapy with piperacillin/tazobactam or cefepime in combination with aminoglycoside might be more useful for febrile neutropenic children, instead of β-lactam monotherapy in institutions with high prevalence of ESBL-producing E. coli and K. pneumoniae.