Joint Health Status in Hemophilia Patients Using Hemophilia Joing Health Score and Pettersson Score

Background: Comprehensive clinical and radiologic follow-up is needed to preserve joint functions and quality of life in hemophilia using clinimetric tools such as Hemophilia joint health score (HJHS) or Pettersson score (PS). We investigated the joint health status evaluated using the tools in Korean hemophilia patients. Methods: We reviewed retrospectively medical records to collect clinical parameters, HJHS and PS, who were followed up in Severance Hospital, Seoul, Korea. The correlation between HJHS and PS, and the effect of the prophylaxis for hemophilia on the outcomes measured with the scores were evaluated. The prophylaxis proportion (PP) was calculated as the proportion of prophylaxis duration to each patient’s life time. Results: Total of 28 patients with severe hemophilia were enrolled. Twelve patients (42.8%) were less than 20 years old. Total of 23 patients had experienced prophylaxis during their lives, and median PP was 39.7%. There was significant correlation between HJHS and PS (P＜0.001). Each score was positively correlated with patient’s age (P＜0.001). PP was negatively correlated with either HJHS or PS (P＜0.001, respectively). There was significant correlation between either HJHS or PS and the PP in the group of patients ＜20 years old, but there was no correlation in the group of ＞20 years old. Conclusion: HJHS and PS were positively correlated. Each score increased as the patient’s age increased. The prophylaxis had protective effect on joint health. The prospective evaluation of HJHS and PS will be needed to prove the effect of proper management on the joint health status.ope

망막모세포종 환자를 대상으로 한 동맥 항암 및 전신 항암 병용 요법의 효과

의과대학/석사Intra-arterial chemotherapy (IAC) is one of the current standard treatment of retinoblastoma, however it cannot exclude the risk of occult micrometastases in the central nervous system in advanced stage retinoblastoma. Alternate fashion of IAC and intravenous chemotherapy (IVC) strategy was developed to increase the eye salvage rate and to reduce the metastatic risk. Between January 2012 and December 2014, 13 eyes of 12 patients with newly diagnosed retinoblastoma received alternate IAC and IVC in Yonsei Cancer Center. Eye salvage rate was assessed by the eye preservation time which was defined as the duration from the diagnosis to the time of enucleation. Total 13 eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group B (n = 1), group C (n = 2), group D (n = 5), or group E (n = 5). IAC was performed three to five times for each eye, total 54 times. Five to fifteen courses of IVC were performed. During the median follow-up period of 30.4 months, overall eye salvage rate was 63.9 ± 14.7%. All patients survived. The treatment was tolerable without significant complications. Primary alternate IAC-IVC was tolerable and effective for retinoblastoma.ope

Loss of Heterozygosity at Chromosome 16q Is a Negative Prognostic Factor in Korean Pediatric Patients with Favorable Histology Wilms Tumor: A Report of the Korean Pediatric Hematology Oncology Group (K-PHOG)

Purpose: Loss of heterozygosity (LOH) at chromosomes 1p and 16q is a poor prognostic factor in favorable histology Wilms tumor (FHWT). This study investigated the prevalence of LOH at 1p and 16q and evaluated its prognostic value in Korean children with FHWT. Materials and methods: We analyzed 101 FHWT patients who were diagnosed between 1996 and 2016 in Korean Society of Pediatric Hematology Oncology Group hospitals. Using paraffin-embedded kidney tissue samples sent from each center, we reviewed LOH at 1p and 16q in each patient and assessed the prognostic value of LOH status for clinical parameters affecting event-free survival (EFS). Results: Of the 101 patients, 12 (11.9%) experienced recurrence; the 3-year EFS was 87.6%. LOH at 1p or 16q was detected in 19 patients (18.8%), with five having LOH at both 1q and 16q. The frequency of LOH at 1p was higher among younger patients (p=0.049), but there was no difference in LOH prevalence according to tumor stage. In the multivariate analysis, LOH at 16q was a significant negative prognostic factor affecting EFS (3-year EFS, 73.7% vs. 91.1%; hazard ratio, 3.95; p=0.037), whereas LOH at 1p was not (p=0.786). Conclusion: LOH at 16q was a significant negative prognostic factor affecting outcome in Korean pediatric FHWT patients. Due to the small sample size of this study, large-scale multicenter trials are warranted to investigate the prognostic value of LOH at 1p and 16q in Korean children with FHWT.ope

Effectiveness and Safety of Clofarabine Monotherapy or Combination Treatment in Relapsed/Refractory Childhood Acute Lymphoblastic Leukemia: A Pragmatic, Non-interventional Study in Korea

Purpose: Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development. Materials and methods: In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed. Results: Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events. Conclusion: Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.ope

Osteonecrosis in Korean Paediatric and Young Adults with Acute Lymphoblastic Leukaemia or Lymphoblastic Lymphoma: A Nationwide Epidemiological Study

Osteonecrosis (ON) is a serious complication of acute lymphocytic leukaemia (ALL) or lymphoblastic lymphoma (LBL) treatment, and there is little information regarding ON in Korean paediatric and young adult patients. This retrospective cohort study assessed the cumulative incidence of and risk factors for ON using national health insurance claims data from 2008 to 2019 in 4861 ALL/LBL patients. The Kaplan-Meier method was used to estimate the cumulative incidence of ON according to age groups; the Cox proportional hazard regression model was used to identify risk factors related to ON development after diagnosing ALL/LBL. A cause-specific hazard model with time-varying covariates was used to assess the effects of risk factors. Overall, 158 (3.25%) patients were diagnosed with ON, among whom 23 underwent orthopaedic surgeries. Older age, radiotherapy (HR = 2.62, 95% confidence interval (CI) 1.87-3.66), HSCT (HR = 2.40, 95% CI 1.74-3.31), steroid use and anthracycline use (HR = 2.76, CI 1.85-4.14) were related to ON in the univariate analysis. In the multivariate analysis, age and steroid and asparaginase use (HR = 1.99, CI 1.30-3.06) were factors associated with ON. These results suggest that Korean patients with ALL/LBL who used steroids and asparaginase should be closely monitored during follow-up, even among young adult patients.ope

A Case of Successfully Treated Severe Heart Failure .due to Cyclophosphamide Induced Cardiomyopathy

Cyclophosphamide-induced cardiotoxicity is an uncommon complication especially in patients who have never undergone mediastinal irradiation or cardiotoxic chemotherapy and do not have underlying cardiac diseases. Here, we describe the case of a 19-year-old female with chronic myeloid leukemia. She was previously treated with oral tyrosine kinase inhibitors and developed cardiomyopathy after receiving infusion of 60 mg/kg intravenous cyclophosphamide for two days with a conditioning regimen for allogenic hematopoietic stem cell transplantation. Severe thickening of the left ventricle and reduced ejection fraction without triggering agents were characteristic for cyclophosphamide-induced cardiomyopathy. Her NT-pro BNP and troponin T concentrations surged to ＞70,000 pg/mL (0=130 pg/mL) and 2,031 pg/mL (0-14 pg/mL), respectively, during the course of the therapy and multiple organ failure seemed imminent evidenced by unresponsive decline in blood pressure. However, with close monitoring and persistent conservative management which consisted of intravenous hydration, continuous hemodialysis, and mechanical ventilation, her condition recovered.ope

Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years

Purpose: Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for central nervous system ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years. Materials and methods: A search of medical records from seven centers was performed between January 2005 and December 2016. Results: Forty-three patients were enrolled. With a median follow-up of 90 months, 27 patients (64.3%) showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3-year progression-free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3-year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n=21), treatment-related toxicity (n=5), or unknown cause (n=1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high-dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p < 0.01). Conclusion: Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.ope

Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group

Purpose: Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. Materials and methods: Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. Results: Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). Conclusion: This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.ope

Surgical Procedures Requiring Hospitalization and Perioperative Management for Patients with Hereditary Bleeding Disorders

Background: Hemophilia requires a lifetime care for bleeding control and complications. Although patients diagnosed with hemophilia receive factor replacement, they also experience a variety of medical problems as they age. Elective surgery can be performed through appropriate factor replacement during and after surgery. However, for patients with inhibitors, this remains a problem to be overcome. Methods: Patients treated for congenital bleeding disorders between 2008 and 2021 were enrolled in this study. The patients were classified according to the type, severity, and presence of inhibitors. The patients underwent planned coagulation factor replacement depending on the type of surgery. Results: A total of 232 patients treated for congenital bleeding disorders were enrolled. Among them hemophilia A was most prevalent, followed by hemophilia B. In total, 78 of the patients underwent surgery, including 31 major and 55 minor surgeries. Orthopedic surgery was the most common surgery, and patients with inhibitors had significantly more postoperative hospitalization days. Nine patients were incidentally diagnosed. Twelve patients with hemophilia with inhibitors underwent surgery, and 6 of them experienced post-operative complications. Conclusion: Proper surgical planning and monitoring with a multidisciplinary team will be required for appropriate perioperative management of patients with hemophilia, especially in patients with inhibitor and elderly hemophilia patients.ope

Primary Extragonadal Germ Cell Tumors in Klinefelter Syndrome: 10-Years of Experience from a Single Institute

Background: Approximately 8% of male patients presenting with primary mediastinal germ cell tumors (GCTs) have Klinefelter syndrome (KS), while patients diagnosed with retroperitoneal GCTs also exhibit a range of chromosomal abnormalities. The exact mechanism underlying the development of GCTs in Klinefelter syndrome is unknown, but KS frequently goes underdiagnosed as a result of its varied symptoms and a low general awareness of this condition. Thus, the Children’s Oncology Group recommends screening of Klinefelter syndrome in pediatric and adolescent male subjects who present with GCTs. Methods: We retrospectively reviewed the medical records of extragonadal germ cell tumor patients treated at Severance hospital, department of pediatrics or division of pediatric hematology-oncology over the last ten years. Results: A total of 95 patients with extragonadal germ cell tumors were included in this study. Karyotyping was done in eight patients out of 95 patients, three patients with KS and one patient with Down syndrome. Twelve of extragonadal GCT patients presented at mediastinum, with most common histology of mature teratoma, and three patients presented with chromosomal abnormalities, two with KS and one with Down syndrome. A total of nine patients were diagnosed with retroperitoneal GCTs and only one had KS. Conclusion: We described the characteristics of 95 cases of extragonadal GCTs. Although the mechanism of extragonadal GCTs in KS is not clear, karyotyping in pediatric and adolescent extragonadal GCT patients could be helpful in figuring out chromosomal abnormalities including KS and their roles in GCT pathophysiology, which can contribute to improve one’s health.ope