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.
Anthracyclines ; Cardiotoxicity ; Dexrazoxane ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Korea ; Multivariate Analysis ; Neoplasms, Second Primary ; Risk Factors* ; Stem Cell Transplantation

BACKGROUND: Although some strategies are used for prophylaxis of contrast induced nephropathy, their efficacy is not fully established. Sarpogrelate can relieve vasospasm and have anti-inflammatory action. This study examined whether sarpogrelate reduces the incidence of contrast induced nephropathy (CIN) or subsequent renal impairment during four weeks after coronary angiography compared with a control group. METHODS: Seventy-four participants with chronic renal failure were randomly assigned to the sarpogrelate or control group. Patients assigned to the sarpogrelate group received oral saporogelate from 24 hours before contrast exposure up to one month after contrast exposure. The primary outcome of this study was the incidence of CIN within 48 hours after exposure to the contrast agent. RESULTS: Thirty-one subjects in the control group and 35 subjects in the sarpogrelate group were used for the analysis. Cumulative CIN occurred numerically more at 48 hours in the sarpogrelate group and less at one month without statistical significance (11.4% vs. 6.5% at 48 hours and 11.4% vs. 16.1% at one month, respectively). Baseline renal function was similar in both groups, but the estimated glomerular filtration rate (eGFR) was lower in the sarpogrelate group at 12 and 48 hours compared with the control group (45.6 vs. 54.7 mL/min/1.73m²; P = 0.023 and 39.9 vs. 50.6 mL/min/1.73m²; P = 0.020, respectively). At one month, the eGFR became comparable between the two groups because the eGFR was aggravated in the control group and maintained in the sarpogrelate group. CONCLUSION: This study failed to demonstrate that sarpogrelate has a renoprotective effect against contrast induced acute kidney injury. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01165567
Acute Kidney Injury ; Coronary Angiography ; Glomerular Filtration Rate ; Humans ; Incidence ; Kidney Failure, Chronic ; Prospective Studies ; Renal Insufficiency ; Serotonin

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.
Anemia, Hemolytic, Autoimmune ; Cell Transplantation* ; Child* ; Diagnosis ; Humans ; Immunoglobulins ; Incidence ; Korea ; Pediatrics ; Purpura, Thrombocytopenic, Idiopathic ; Rituximab ; Transplants* ; Unrelated Donors

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.
Cell Transplantation ; Chromosome Aberrations ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Fluorescence ; Humans ; In Situ Hybridization ; Incidence ; Korea* ; Multivariate Analysis ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Prognosis ; Recurrence ; Remission Induction ; Transplants

Stent migration and loss are rare but can be devastating complications during percutaneous coronary intervention (PCI) for coronary artery disease. We report a unique case of wandering stent from the right coronary artery to the femoral artery via the axillary artery. Initially, the stent was stripped from the delivery catheter and embolized to axillary artery during emergent PCI. An intra-aortic balloon pump might have forced retrograde movement of the stent to axillary artery which have subsequently remobilized to the femoral artery. After stabilization, the stent was successfully removed by a percutaneous approach using a snare. Immediate retrieval of wandering stent is recommended for the prevention of secondary embolization.
Axillary Artery* ; Catheters ; Coronary Artery Disease ; Coronary Vessels ; Drug-Eluting Stents ; Embolism ; Femoral Artery* ; Percutaneous Coronary Intervention ; SNARE Proteins ; Stents*

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.
Acyclovir* ; Cell Transplantation ; Chickenpox* ; Child* ; Hematologic Neoplasms* ; Herpes Zoster ; Herpesvirus 3, Human* ; Humans ; Leukemia ; Lymphoma ; Medical Records ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Transplants

BACKGROUND: The incidence of bacteremia caused by Gram-negative bacteria has increased recently in febrile neutropenic patients with the increase of antibiotic-resistant Gram-negative bacterial infections. This study aimed to identify the distribution of causative bacteria and the proportion of antibiotic-resistant bacteria in bacteremia diagnosed in febrile neutropenic children. MATERIALS AND METHODS: The medical records of febrile neutropenic children diagnosed with bacteremia between 2010 and 2014 were retrospectively reviewed. The causative bacteria and proportion of antibiotic-resistant bacteria were investigated and compared yearly during the study period. The clinical impact of antibiotic-resistant bacterial infections was also determined. RESULTS: A total of 336 bacteremia episodes were identified. During the entire study period, 181 (53.9%) and 155 (46.1%) episodes were caused by Gram-negative and Gram-positive bacteria, respectively. Viridans streptococci (25.9%), Klebsiella spp. (16.7%), and Escherichia coli (16.4%) were the most frequent causative bacteria. The overall distribution of causative bacteria was not significantly different annually. Antibiotic-resistant bacteria were identified in 85 (25.3%) episodes, and the proportion of antibiotic-resistant bacteria was not significantly different annually. Extended-spectrum β-lactamase-producing E. coli and Klebsiella spp. were most common among antibiotic-resistant Gram-negative bacteria, and they accounted for 30.6% (n = 34) of the identified E. coli and K. pneumoniae. Methicillin-resistant coagulase-negative staphylococci were most common among antibiotic-resistant Gram-positive bacteria, and it accounted for 88.5% (n = 23) of the identified coagulase-negative staphylococci. Antibiotic-resistant bacterial infections, especially antibiotic-resistant Gram-negative bacterial infections, caused significantly higher mortality due to bacteremia compared with non-antibiotic-resistant bacterial infections (P <0.001). CONCLUSION: Recently, Gram-negative bacteria caused more bacteremia cases than Gram-positive bacteria in febrile neutropenic children, and antibiotic-resistant Gram-negative bacterial infections increased. Antibiotic-resistant bacterial infections caused poorer prognosis compared with non-antibiotic-resistant bacterial infections, and therefore, continuous surveillance for changing epidemiology of antibiotic-resistant bacterial infections and their clinical impact is necessary.
Bacteremia ; Bacteria ; Bacterial Infections ; Child* ; Drug Resistance, Microbial ; Epidemiology ; Escherichia coli ; Fever ; Gram-Negative Bacteria ; Gram-Negative Bacterial Infections* ; Gram-Positive Bacteria ; Humans ; Incidence ; Klebsiella ; Medical Records ; Methicillin Resistance ; Mortality ; Neutropenia ; Pneumonia ; Prognosis ; Retrospective Studies ; Viridans Streptococci

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.
Antifungal Agents/*therapeutic use ; Child ; Child Health/statistics & numerical data ; Comorbidity ; Female ; Hematologic Diseases/*mortality ; Humans ; Incidence ; Invasive Pulmonary Aspergillosis/*diagnosis/drug therapy/*mortality ; Male ; Neoplasms/*mortality ; Prognosis ; Republic of Korea/epidemiology ; Risk Factors ; Survival Rate ; Tomography, X-Ray Computed/statistics & numerical data ; Treatment Outcome

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.
Abdominal Pain ; Acyclovir ; Chickenpox* ; Child* ; Disease Progression ; Disseminated Intravascular Coagulation ; Drug Therapy ; Hepatitis ; Herpesvirus 3, Human ; Humans ; Immunocompromised Host ; Immunoglobulins* ; Mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Respiratory Distress Syndrome, Adult ; Viremia

PURPOSE: The use of cyclosporine and mini-dose methotrexate (MTX) is a common strategy for graft-versus-host disease (GVHD) prophylaxis in allogeneic transplants. We investigated whether patients who receive fewer than the planned MTX doses are at increased risk for GVHD. METHODS: The study cohort included 103 patients who received allogeneic transplants at the Department of Pediatrics of The Catholic University of Korea College of Medicine, from January 2010 to December 2011. MTX was administered on days 1, 3, 6, and 11 after transplant at a dose of 5 mg/m2 each. Within the cohort, 76 patients (74%) received all 4 doses of MTX [MTX(4) group], while 27 patients (26%) received 0-3 doses [MTX(0-3) group]. RESULTS: Although there was no difference in neutrophil engraftment between the 2 groups, platelet engraftment was significantly faster in the MTX(4) group (median, 15 days), compared to the MTX(0-3) group (median, 25 days; P=0.034). The incidence of grades II-IV acute GVHD was not different between the MTX(4) and MTX(0-3) groups (P=0.417). In the multivariate study, human leukocyte antigen mismatch was the most significant factor causing grades II-IV acute GVHD (P=0.002), followed by female donor to male recipient transplant (P=0.034). No difference was found between the MTX(4) and MTX (0-3) groups regarding grades III-IV acute GVHD, chronic GVHD, and disease-free survival. CONCLUSION: Our results indicate that deviations from the full dose schedule of MTX for GVHD prophylaxis do not lead to increased incidence of either acute or chronic GVHD.
Appointments and Schedules ; Blood Platelets ; Child* ; Cohort Studies ; Cyclosporine ; Female ; Graft vs Host Disease* ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Incidence ; Korea ; Leukocytes ; Male ; Methotrexate* ; Neutrophils ; Pediatrics ; Tissue Donors