Can we Predict the Clinical Course of Immune Thrombocytopenia in Children by The Mean Platelet Volume? A Preliminary Study.

BACKGROUND: Mean platelet volume (MPV) is considered a marker of platelet function and is known to increase in immune thrombocytopenia (ITP). We aimed to investigate the predictive value of MPV for predicting the clinical course of ITP in children. METHODS: We retrospectively analyzed children aged < 18 years with ITP (n = 36) and healthy controls (n = 36) from June 2010 to November 2018. The subjects were stratified into: (i) Healthy controls [group I, n = 36]; (ii) Newly diagnosed ITP (nITP) and persistent ITP (pITP) [group II, n = 24]; and (iii) Chronic ITP (cITP) [group III, n = 12]. Hematological indices including MPV were measured and compared between the three groups. RESULTS: The median MPV values at diagnosis in group I, II, and III were 7.20, 8.15, and 8.65 fL, respectively (p = 0.0004). Cutoff value of MPV at diagnosis differentiating group I from group II + III was 7.6 fL, and group II from group III was 8.7 fL. MPV change (ΔMPV after three months minus MPV at diagnosis) in children with nITP and pITP (n = 22) was greater than in those with cITP (n = 6) (-2.18 fL vs. 0.66 fL, p = 0.0059). CONCLUSIONS: This study revealed that group III had a higher MPV than group II at diagnosis. Therefore, an initial MPV value more than 8.7 fL may be used as a predictive factor for chronicity in children with ITP. The change in MPV over time as well as MPV at diagnosis, may be regarded as a prognostic marker to predict the course of ITP in children.

Usefulness of Routine Coagulation Tests in Healthy Children Undergoing Elective Minor Surgery: a 12-Year Retrospective Study.

BACKGROUND: Although routine coagulation tests, such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) are performed before surgery to identify the risk of perioperative bleeding, bleeding complications are rare in minor surgeries, and false-positive results are often observed. Therefore, this study aimed to analyze the common causes of abnormal results of preoperative coagulation tests in previously healthy children undergoing elective minor surgery and determine the usefulness of performing these tests. Additionally, it aimed to identify the distribution of factor XII activity in children with prolonged aPTT. METHODS: The medical records of 363 pediatric patients aged 0 - 18 years, who were referred to the pediatric hematology-oncology department due to abnormal preoperative coagulation tests prior to undergoing minor surgery at the Kyung Hee University Medical Center between March 2008 and October 2020, were retrospectively review-ed. RESULTS: The majority of patients (n = 348, 96%) had prolonged aPTT, few (n = 29, 8%) had a prolonged PT international normalized ratio, and a small number (n = 14, 4%) had both prolonged PT and aPTT. On repeating the coagulation tests, 194 children showed persistent abnormal results. Of these, 184 patients underwent mixing tests, and 176 showed correction for factor deficiency (n = 26) and lupus anticoagulant positive (n = 14). Factor deficiencies included factor XII (n = 16), possibility of von Willebrand disease (vWD; n = 4), factor XI (n = 2), factor VIII (n = 1), factors IX and XII (n = 1), factor VII (n = 1), and factor V (n = 1). The severity of factor deficiency was mild (25 - 38%). One patient with factor VII deficiency received preoperative clotting factors but had postoperative bleeding requiring clotting factor replacement. Another patient with possible vWD received fresh frozen plasma after surgery and had mild symptoms. Linear regression showed no significant correlation between factor XII activity and aPTT in patients with prolonged aPTT (R2 = 0.0002, p = 0.84) or factor XII activity according to aPTT results in those with factor XII deficiency (R2 = 0.04749, p = 0.40). CONCLUSIONS: These results suggest that coagulation tests may be selectively performed in previously healthy children undergoing minor surgery with positive bleeding and/or family history. The distribution of factor XII should be investigated further.

Rapid weight gain in early life is associated with severity of respiratory syncytial virus (RSV) bronchiolitis in children.

OBJECTIVES: This study aimed to investigate whether rapid weight gain in early life was associated with the severity of respiratory syncytial virus (RSV) bronchiolitis in children. METHODS: We retrospectively reviewed 190 patients (1-24 months) hospitalized for RSV bronchiolitis. Parameters of bronchiolitis severity were compared between rapid (change in weight z-score from birth >0.67, n = 65) and normal weight gain groups (n = 125). We assessed for correlations between bronchiolitis severity and weight gain. Linear regression was performed to predict for bronchiolitis severity based on weight gain, controlling for covariates. SPSS was used for statistical analyses. RESULTS: The rapid weight gain group had longer mean durations of tachypnea (2.3±2.0 vs. 1.7±1.8 days, P = 0.027), wheezing (3.2±2.5 vs. 1.6±1.8 days, P < 0.001), and chest retractions (1.5±2.2 vs. 0.6±1.3 days, P = 0.007). Correlations of weight gain with tachypnea (r = 0.146), wheezing (r = 0.279), and chest retractions (r = 0.179) were statistically significant. Weight gain predicted for tachypnea (B = 0.485, P = 0.013) and wheezing (B = 0.846, P = 0.001) durations after adjusting for covariates of severity (age, sex, current weight, RSV type, coinfection, recurrent bronchiolitis, hospital stay, fever, oxygen supplementation, maximal respiratory and heart rates, and laboratory indices). CONCLUSIONS: Our findings suggest an association between weight gain and severity of RSV bronchiolitis in young children. Weight gain was significantly associated with the durations of tachypnea and wheezing. The trajectory of weight gain in early life may play a significant role in the clinical course of RSV bronchiolitis.

Serum cytokine profiles in infants with infantile hemangiomas on oral propranolol treatment: VEGF and bFGF, potential biomarkers predicting clinical outcomes.

BACKGROUND: Oral propranolol has become first-line treatment for infantile hemangiomas (IHs). This study focused on identifying cytokines related to the biology of IH and early regression indicators of IH after propranolol treatment. METHODS: For inclusion, the patients had to be aged less than 1 year and have an IH with a largest diameter ≥2 cm. Patients were scheduled to receive 1 year of propranolol treatment. Serum cytokines involved in angiogenesis, vasculogenesis, and/or chronic inflammation were analyzed at 0, 1, and/or 12 months after treatment using Multiplex Luminex assays. RESULTS: Among the 49 evaluable patients, 33 completed the 1-year treatment: 16 showed excellent response and 12 had good response to propranolol. Significant decreases in serum MMP-2, bFGF, VEGF-α, and MCP-1 levels were observed after 1 year of treatment compared to pretreatment values. The maximal diameters of the lesions significantly correlated with pretreatment serum VEGF-α, bFGF, and MMP-9. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. CONCLUSION: MMP-2, VEGF-α, bFGF, and MCP-1 may involve in the biology of IH and their downregulation may be associated with involution processes of IH. Pretreatment bFGF and VEGF could be novel biomarkers for predicting response to propranolol. IMPACT: We found that decreases in the concentrations of MMP-2, bFGF, VEGF, and MCP-1 were associated with regression of the hemangioma, which indicates that one of the mechanisms of propranolol in the treatment of proliferative hemangiomas may involve downregulation of those cytokines. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. Importantly, serum bFGF higher than 37.07 pg/mL may predict an excellent response to propranolol. Therefore, along with the patient's age and the size and visual characteristics of the lesion, bFGF levels could help determine the viability of propranolol use in the treatment of IHs. Our study represented extensive serum profiling in IH, reporting the indicators and molecules clearly related to IH regression with propranolol treatment. The authors believe that monitoring serum cytokines, including MMP-2, bFGF, VEGF, and MCP-1, in IH patients could be important, in addition to clinical follow-up, for determining when to start and end propranolol treatment.

Epidemiology of Congenital Bleeding Disorders: a Nationwide Population-based Korean Study.

BACKGROUND: Except for data in the Korea Hemophilia Foundation Registry, little is known of the epidemiology of congenital bleeding disorders in Korea. METHODS: Data were obtained from the Korean Health Insurance Review and Assessment Service (HIRA) database. RESULTS: From 2010 to 2015, there were 2,029 patients with congenital bleeding disorders in the Korean HIRA database: 38% (n = 775) of these patients had hemophilia A (HA), 25% (n = 517) had von Willebrand disease (vWD), 7% (n = 132) had hemophilia B (HB), and 25% (n = 513) had less common factor deficiencies. The estimated age-standardized incidence rate (ASR) of HA and HB was 1.78-3.15/100,000 and 0.31-0.51/100,000, respectively. That of vWD was 1.38-1.95/100,000. The estimated ASR of HA showed increase over time though the number of new patients did not increase. Most patients with congenital bleeding disorders were younger than 19 years old (47.8%), and most were registered in Gyeonggi (22.1%) and Seoul (19.2%). CONCLUSION: This is the first nationwide population-based study of congenital bleeding disorders in Korea. This study provides data that will enable more accurate estimations of patients with vWD. This information will help advance the comprehensive care of congenital bleeding disorders. We need to continue to obtain more detailed information on patients to improve the management of these diseases.

Langerhans Cell Histiocytosis of the Gastrointestinal Tract: Evidence for Risk Organ Status.

OBJECTIVE: To investigate the "risk status" of Langerhans cell histiocytosis (LCH) of the gastrointestinal tract. STUDY DESIGN: Outcomes from 43 published cases of patients with LCH and gastrointestinal tract involvement were matched to 43 patients with LCH without gastrointestinal tract involvement cared for at our institution. Comparisons were made of the 5-year overall survival rates determined from Kaplan-Meier survival curves for the entire cohort of patients, as well as subgroups defined by lack of risk organ involvement and later era of treatment (to control for temporal changes in LCH treatment regimens). In addition, an association between LCH-gastrointestinal tract and risk organ involvement was investigated. RESULTS: The 5-year overall survival for children with LCH-gastrointestinal tract (45.3%) was significantly worse than for those without gastrointestinal tract involvement (94.6%; P = .001). This difference remained significant after we excluded risk organ involvement (53.6%% vs 100%; P = .001), and analyzing subjects diagnosed after 2000 (75% vs 100%; P = .012). A 4-fold increase in risk organ involvement with LCH-gastrointestinal tract was observed (OR 4.359; 95% CI 1.75-10.82, P = .001). CONCLUSIONS: This limited retrospective study suggests that patients with LCH-gastrointestinal tract involvement may have decreased survival, independent of risk organ involvement, and provides evidence to support a prospective study to evaluate risk organ status of LCH-gastrointestinal tract. LCH-gastrointestinal tract may be associated with a 4-fold risk for risk organ involvement. Attention to gastrointestinal symptoms and LCH-gastrointestinal tract in young children diagnosed with LCH is warranted.

Prospective case control study of iron deficiency and the risk of febrile seizures in children in South Korea.

BACKGROUND: Febrile seizures are the most common type of seizure in the first 5 years of life, and many factors that increase seizure risk have been identified. This study was performed to examine the association between iron status and febrile seizures in children in South Korea. METHODS: A prospective unmatched case control study was performed in 63 cases of febrile seizures and 65 controls with febrile illness but no seizures. RESULTS: Serum iron, plasma ferritin, and transferrin saturation were significantly lower in children with febrile seizures compared to the controls. Iron deficiency, defined as ferritin < 30 ng/mL, was more prevalent in the febrile seizure group (49.2%) than in the control group (16.9%). Serum iron < 22 ng/dL (odds ratio 3.42, 95% confidence interval [CI] 1.31-8.9, P = 0.012) and ferritin < 30 ng/mL (odds ratio 6.18, 95% CI 2.32-16.42, P < 0.001) were associated with increased risk of developing febrile seizures in multivariate logistic regression analysis. CONCLUSION: These observations suggest that iron deficiency prior to development of anemia may increase risk of febrile seizures.

Higher Gemcitabine Dose Was Associated With Better Outcome of Osteosarcoma Patients Receiving Gemcitabine-Docetaxel Chemotherapy.

BACKGROUND: Efficacy of gemcitabine and docetaxel (GEM + DOC) chemotherapy in patients with recurrent or refractory osteosarcoma was evaluated. METHODS: Data of 53 patients from 9 institutions, who received GEM (675 or 900 mg/m(2) on days 1 and 8) and DOC (100 mg/m(2) on day 8), were retrospectively reviewed. RESULTS: GEM + DOC was administered as adjuvant (n = 25) or palliative chemotherapy (n = 28). Patients received a median 3 courses (range, 1-10 courses). Objective response rate (CR + PR, where CR is complete response and PR is partial response) and disease control rate (CR+ PR + SD, where SD is stable disease) were 14.3% and 28.6%, respectively. Disease control rate was higher in patients receiving 900 mg/m(2) GEM than in patients receiving 675 mg/m(2) (50.0% vs. 12.5%, P = 0.03). Higher GEM dose was associated with better survival, both in adjuvant (1-year overall survival, 90.9 ± 8.7% vs. 38.5 ± 13.5%, P = 0.002) and palliative settings (50.0 ± 14.4% vs. 31.3 ± 11.6%, P = 0.04). CONCLUSIONS: Further studies are necessary to investigate the efficacy of more aggressive and higher doses of GEM + DOC chemotherapy in osteosarcoma.

Should healthy children who will undergo minor surgery be screened for coagulation disorder?

The objective of this study is to analyze the major causes of abnormal findings seen in the preoperative coagulation tests of asymptomatic pediatric patients and to discuss the usefulness of coagulation tests prior to minor surgery. Among patients who received minor surgery in Kyung Hee University Medical Center from March 2008 to April 2015, a total of 7114 pediatric patients (ages 1-18) were included in our study. Of these, 226 (3.1%) were referred to the pediatrics hematology-oncology department because of abnormal preoperative coagulation tests. A review of the coagulation tests indicate the majority (n = 216, 95.5%) have prolonged activated partial thromboplastin time (aPTT), whereas a smaller number (n = 10, 4.5%) have prolonged prothrombin time international normalized ratio (PT INR). When the coagulation tests were repeated, 136 displayed abnormal findings again. Of these 136 patients, 128 patients underwent mixing tests, and 127 showed results of correction and were composed as follows: normal (n = 83), subnormal (n = 26), factor deficiency (n = 15), and lupus anticoagulant positive (n = 3). Breakdown by factor deficiencies was as follows: (i) factor XII (n = 9), (ii) factor IX (n = 2), (iii) factors XII and IX (n = 1), (iv) factor VIII (n = 1), (v) factor XI (n = 1), (vi) von Willebrand factor (vWF; n = 1), and (vii) factor V (n = 1). Each factor activity range was mild (21%-39%), so no patients received preoperative medications or clotting factors/blood products. Even in the presence of factor deficiencies, bleeding symptoms were mild and postoperative complications did not occur. These results suggest that coagulation tests may not be needed in healthy children and should be reserved for patients with positive bleeding and/or family history.

Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party.

BACKGROUND: We analyzed a nationwide registry of pediatric patients with hemophagocytic lymphohistiocytosis (HLH) in Korea to assess the clinical and genetic features and treatment outcomes in pediatric HLH. METHODS: The Korea Histiocytosis Working Party retrospectively analyzed data on 251 pediatric patients diagnosed with HLH between 1996 and 2011. RESULTS: In the study cohort, 25 cases were categorized with familial HLH, 64 with presumed secondary HLH, and 162 with unspecified HLH. Of 217 evaluable patients, 91 (42%) had concomitant Epstein-Barr virus infection. Of 238 evaluable patients, central nervous system (CNS) involvement, which was more frequent in the familial group, was evident in 81 cases (34%). Genetic tests revealed a predominant UNC13D mutation with a high incidence of two recurrent splicing mutations (c.118-308C>T and c.754-1G>C). The 5-yr overall survival rate was 68% (38% in the familial group and 81% in the presumed secondary group). The 5-yr overall survival rate among 32 patients who underwent allogeneic hematopoietic stem cell transplantation was 64%. In multivariate analysis, a younger age at diagnosis, severe transaminasemia, and a coagulation abnormality were independent prognostic factors for survival. Responses during initial treatments were also significant indicators of outcome. CONCLUSION: Our study showed the unique predominance of a UNC13D mutation and vulnerability to Epstein-Barr virus infection in Korean children with HLH and emphasizes the prognostic significance of age, liver dysfunction, and treatment responses in this disease. A multicenter prospective trial that builds on the present results is warranted to identify subgroups of patients with a poor prognosis and identify optimal treatments.

Hepatic angiosarcoma mimicking congenital cytomegalovirus infection in an infant with thrombocytopenia.

Hepatic angiosarcomas are uncommon, highly aggressive tumors, rarely seen in children. A 3-month-old female infant was admitted to hospital for evaluation of multiple petechiae on her body. She had hepatosplenomegaly and scattered petechiae over her entire body. Laboratory tests indicated thrombocytopenia and positive cytomegalovirus (CMV) polymerase chain reaction. Ganciclovir was started, and the platelet count increased. After 4 months the patient was readmitted to hospital for drowsy mental status and eventually died from severe bleeding. Needle biopsy of the liver was performed after receiving written consent from the parents. Pathological findings of the liver lesion included features consistent with hepatic angiosarcoma. There have been no previous reports of hepatic angiosarcoma in Korean infants. Here, we report an infant with hepatosplenomegaly and thrombocytopenia who was diagnosed with hepatic angiosarcoma mimicking congenital CMV infection.

Recent change in congenital syphilis in Korea: Retrospective 10 year study.

BACKGROUND: This study was conducted to evaluate recent clinical and anthropologic features of neonates with reactive serology for syphilis and their mothers from three institutions in Korea over an 11-year-period. METHOD: The medical records of 20 neonates with reactive serology for syphilis and their mothers at three centers (Kyung Hee University Hospital, Kyung Hee University Hospital at Gangdong, and Korea Electric Power Corporation Hospital) seen between January 2000 and December 2010 were reviewed retrospectively. RESULTS: Among 20 mothers, 16 (80%) were native Korean and four (20%) were foreign-born immigrants. Two mothers (10%) were unmarried. The annual distribution of cases was three (15%) in 2000, one each (5%) in 2005 and 2006, respectively, two each (10%) in 2007 and 2008, respectively, six (30%) in 2009, and five (25%) in 2010. Just over half (55%) occurred across 2009 and 2010. All neonates, by definition, were diagnosed with presumptive congenital syphilis (CS). Among the neonates, four had positive cerebrospinal fluid venereal disease research laboratory test, and three exhibited symptoms and signs. CONCLUSIONS: In three centers in Seoul, Korea, the observed number of CS cases was higher in 2009 and 2010 than in previous years. This finding is consistent with a trend toward increasing prevalence of international marriage and suggests that more meticulous screening of CS is needed.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

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.

Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data.

PURPOSE: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. MATERIALS AND METHODS: From January 2001 to December 2015, data of pediatric patients (0-18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. RESULTS: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). CONCLUSION: The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

A comparison of logistic regression analysis and an artificial neural network using the BI-RADS lexicon for ultrasonography in conjunction with introbserver variability.

To determine which Breast Imaging Reporting and Data System (BI-RADS) descriptors for ultrasound are predictors for breast cancer using logistic regression (LR) analysis in conjunction with interobserver variability between breast radiologists, and to compare the performance of artificial neural network (ANN) and LR models in differentiation of benign and malignant breast masses. Five breast radiologists retrospectively reviewed 140 breast masses and described each lesion using BI-RADS lexicon and categorized final assessments. Interobserver agreements between the observers were measured by kappa statistics. The radiologists' responses for BI-RADS were pooled. The data were divided randomly into train (n = 70) and test sets (n = 70). Using train set, optimal independent variables were determined by using LR analysis with forward stepwise selection. The LR and ANN models were constructed with the optimal independent variables and the biopsy results as dependent variable. Performances of the models and radiologists were evaluated on the test set using receiver-operating characteristic (ROC) analysis. Among BI-RADS descriptors, margin and boundary were determined as the predictors according to stepwise LR showing moderate interobserver agreement. Area under the ROC curves (AUC) for both of LR and ANN were 0.87 (95% CI, 0.77-0.94). AUCs for the five radiologists ranged 0.79-0.91. There was no significant difference in AUC values among the LR, ANN, and radiologists (p > 0.05). Margin and boundary were found as statistically significant predictors with good interobserver agreement. Use of the LR and ANN showed similar performance to that of the radiologists for differentiation of benign and malignant breast masses.

UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis is a fatal disease characterized by immune dysregulation from defective function of cytotoxic lymphocytes. Three causative genes have been identified for this autosomal recessive disorder (PRF1, UNC13D, and STX11). We investigated the molecular genetics of familial hemophagocytic lymphohistiocytosis in Korea. DESIGN AND METHODS: Pediatric patients who fulfilled the HLH-2004 criteria were recruited from the Korean Registry for Histiocytosis. Molecular genetic studies were performed on the patients' DNA samples by direct sequencing of all coding exons and flanking sequences of PRF1, UNC13D, and STX11. RESULTS: Forty patients were studied and familial hemophagocytic lymphohistiocytosis mutations were identified in nine; eight patients had UNC13D mutations (89%) and one had a mutation in PRF1. No patient had a STX11 mutation. Notably, four patients had only one UNC13D mutant allele, suggesting that the other mutation was missed by conventional direct sequencing. All UNC13D mutations were deleterious in nature. One known splicing mutation, c.754-1G>C, was recurrent, accounting for 58% of all the mutant alleles (7/12). Five UNC13D mutations were novel (p.Gln98X, p.Glu565SerfsX7, c.1993-2A>G, c.2367+1G>A, and c.2954+5G>A). The one patient with PRF1 mutation was homozygous for a frameshift mutation (p.Leu364GlufsX93), which was previously reported to be the most frequent PRF1 mutation in Japan. CONCLUSIONS: This is the first investigation on the molecular genetics of familial hemophagocytic lymphohistiocytosis in Korea. The data showed that UNC13D is the predominant causative gene in the Korean population. The identification of mutations missed by conventional sequencing would better delineate the mutation spectrum and help to establish the optimal molecular diagnostic strategy for familial hemophagocytic lymphohistiocytosis in Korea, which might need an RNA-based screening strategy.

The outcome of hematopoietic stem cell transplantation in Korean children with hemophagocytic lymphohistiocytosis.

Chemoimmunotherapy-based treatments have improved the survival of patients with HLH, but outcomes of the patients are still unsatisfactory. We report here the outcome of Korean children with HLH who underwent HSCT, which was analyzed from the data of a nation-wide HLH registry. Retrospective nation-wide data recruitment for the pediatric HLH patients diagnosed between 1996 and 2008 was carried out by the Histiocytosis Working Party of the Korean Society of Hematology. Nineteen patients who received HSCT among the total of 148 enrolled children with HLH were analyzed for the transplant-related variables and events. The probability of five-yr survival after HSCT was 73.3% with a median follow-up of 57. Two months compared to 54.3% for the patients who were treated with chemoimmunotherapy only (p = 0.05). The reasons for HSCT were active disease after eight wk of initial treatment (n = 9), relapsed disease (n = 5), and FHL (n = 5). Fourteen patients are currently alive without disease after HSCT, four patients died of treatment-related events (infection in two and graft failure in two) at early post-transplant period, and one patient died of relapse at one yr post transplantation. The survival of patients who were transplanted because of active disease after eight wk of initial treatment was worse compared to those patients who had inactive state at that time (60.6% vs. 100%, respectively, p = 0.06). Of the four patients who received transplants using cord blood, three died of graft failure (n = 2) and relapse (n = 1). The five-yr probability of survival after HSCT according to the donor type was 85.7% for the MRDs (n = 6), 87.5% for the MUDs (n = 8), and 40% for the MMUDs (n = 5) (p = 0.03). Other variables such as age, CNS involvement at the time of diagnosis, the etiology of HLH (familial or secondary), and the conditioning regimens had no influence on the five-yr OS of the HLH patients who underwent HSCT. HSCT improved the survival of the patients who had familial, relapsed, or severe and persistent SHLH in the Korean nation-wide HLH registry. Although numbers were small, these results are similar to other reports in the literature. The disease state after initial treatment, the stem cell source of the transplant, and the donor type were the important prognostic factors that affected the OS of the HLH patients who underwent HSCT.

Cytomegalovirus infection in children who underwent hematopoietic stem cell transplantation at a single center: a retrospective study of the risk factors.

CMV infection is one of the major causes of morbidity and mortality after HSCT. The aim of this single center retrospective study was to analyze risk factors for CMV infection in pediatric patients who underwent HSCT. We retrospectively reviewed the medical records of 117 pediatric patients who underwent allogeneic HSCT at Asan Medical Center between December 2000 and January 2007. After HSCT, CMV antigenemia was detected by identifying CMV pp65 early antigen in white blood cells. The incidence of CMV antigenemia was 24% (28/117) at a median of 38 days (range: 19-123 days) after HSCT. In multivariate analysis, CMV antigenemia occurred significantly more often in CMV seropositive recipients, patients who received grafts from alternative donors, T-cell depleted grafts, patients on ATG-containing conditioning regimens, or patients who received steroid for acute GVHD (p < 0.05). CMV antigenemia tend to develop earlier in patients who received ATG-containing conditioning regimens (p = 0.09). A second episode of CMV antigenemia was observed in three out of 28 patients (11%). The incidence of CMV disease was 5.9% (7/117) at a median of 97 days (range: 34-120 days). Manifestation of CMV disease included retinitis in two, pneumonitis in two, hepatitis in one, hepatitis with colitis in one, and gastritis in one. Six of the 12 patients (50%) with HG antigenemia (CMV pp65 antigen positivity > or =40 cells) developed clinical CMV disease, a rate that was significantly higher than seen in patients with LG antigenemia (6.25%; p < 0.01). We recommend that patients with these risk factors should carefully undergo regular evaluations for CMV infection. We also suggest that earlier and more aggressive preemptive treatment and serial follow-up of CMV disease is necessary in patients with HG-antigenemia.

Successful treatment of retroperitoneal infantile hemangioendothelioma with Kasabach-Merritt syndrome using steroid, alpha-interferon, and vincristine.

Infantile hemangioendothelioma (IHE) is a rare benign vascular tumor with potentially life-threatening complications. Various therapeutic options have been recommended according to the site, extent, and behavior of the IHE. Because of the slow and unpredictable response to treatment with using a single drug in critically ill patients, there is a tendency to administer drugs in combination to treat this disease. Here, we report on a 1-month-old female infant who had a retroperitoneal IHE with Kasabach-Merritt syndrome and she was successfully treated with a combination of steroid, interferon-alpha, and vincristine.