Safety and effectiveness of Rixubis in patients with hemophilia B:a real-world, prospective, postmarketing surveillance study in South Korea

Background@#Rixubis (recombinant factor IX, nonacog gamma) is indicated for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis in hemophilia B patients. This real-world, postmarketing surveillance study aimed to evaluate the safety and effectiveness of Rixubis in adult and pediatric hemophilia B patients in South Korea. @*Methods@#This prospective, observational, multicenter study (clinicaltrials.gov identifier: NCT029 22231) was conducted in hemophilia B patients between April 2015 and April 2019, who were observed for up to 6 months after the initiation of Rixubis treatment. Safety was evaluated based on the number and severity of adverse events (AEs) and serious AEs (SAEs). Hemostatic effectiveness was assessed by physicians and patients by using a four-point scale and rated as excellent, good, fair, or no response based on treatment type. @*Results@#In all, 58 patients were enrolled from four centers by seven physicians during the study period. The safety and effectiveness analysis sets included 57 and 54 patients, respectively. Overall, 11 AEs were reported in eight patients (14.0%), of which three were SAEs and occurred in three patients (5.3%). All 11 AEs were reported as unexpected and mild in severity, with no anaphylactic reaction, and 10 AEs (90.9%) resolved. The majority of AEs (10) were unrelated to Rixubis. Of the 142 hemostatic effectiveness assessments, 123 (86.6%) were reported as good or excellent. @*Conclusion@#Rixubis demonstrated an acceptable safety and effectiveness profile in the treatment of bleeding, perioperative management, and prophylaxis in hemophilia B patients in a real-world setting in South Korea.

Safety and effectiveness of Rixubis in patients with hemophilia B:a real-world, prospective, postmarketing surveillance study in South Korea

Background@#Rixubis (recombinant factor IX, nonacog gamma) is indicated for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis in hemophilia B patients. This real-world, postmarketing surveillance study aimed to evaluate the safety and effectiveness of Rixubis in adult and pediatric hemophilia B patients in South Korea. @*Methods@#This prospective, observational, multicenter study (clinicaltrials.gov identifier: NCT029 22231) was conducted in hemophilia B patients between April 2015 and April 2019, who were observed for up to 6 months after the initiation of Rixubis treatment. Safety was evaluated based on the number and severity of adverse events (AEs) and serious AEs (SAEs). Hemostatic effectiveness was assessed by physicians and patients by using a four-point scale and rated as excellent, good, fair, or no response based on treatment type. @*Results@#In all, 58 patients were enrolled from four centers by seven physicians during the study period. The safety and effectiveness analysis sets included 57 and 54 patients, respectively. Overall, 11 AEs were reported in eight patients (14.0%), of which three were SAEs and occurred in three patients (5.3%). All 11 AEs were reported as unexpected and mild in severity, with no anaphylactic reaction, and 10 AEs (90.9%) resolved. The majority of AEs (10) were unrelated to Rixubis. Of the 142 hemostatic effectiveness assessments, 123 (86.6%) were reported as good or excellent. @*Conclusion@#Rixubis demonstrated an acceptable safety and effectiveness profile in the treatment of bleeding, perioperative management, and prophylaxis in hemophilia B patients in a real-world setting in South Korea.

Safety and Efficacy of B-domain Deleted Third Generation Recombinant Factor VIII (GreenGene F™) in Korean Patients with Hemophilia A: Data from a Post-marketing Surveillance Study

BACKGROUND: New B-domain deleted third generation recombinant factor VIII (FVIII; GreenGene F™, beroctocog alfa) was launched in 2010. We determined safety and efficacy of GreenGene F™ during routine clinical practice in patients with hemophilia A over a period of 12 months. METHODS: From July 2010 to July 2014, a total of 136 hemophilia A patients were enrolled in a post-marketing surveillance (PMS) study. Among them, 134 patients were assessed for drug safety and 114 patients were analyzed for drug efficacy. Patients with differing hemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on-demand therapy. RESULTS: Among 134 patients evaluated, 85 (63.4%) had severe hemophilia. Ninety-two received a total of 1,266,077 units for prophylaxis, and 42 received 516,491 units for bleeding episodes. Three patients developed inhibitors. In 112 previously treated patients, one patient (0.9%) developed inhibitor after intensive FVIII treatment for surgery. Among 22 previously untreated patients, inhibitors were observed in 2 infants (9.1%). Overall, there were a total of 47 adverse events (other than inhibitors) of all types in 30 patients (22.4%), 11 in 10 patients (7.5%) of which were considered showing serious adverse events (SAEs); most of which were hemorrhages at different sites. None of the SAEs were judged as product related. An excellent/good efficacy rate of 91.3% for hemostasis and 89.4% for hemorrhage prevention was recorded. CONCLUSION: The results of this PMS study support the use of GreenGene F™ as safe and efficacious in hemorrhage prevention and treatment of hemophilia A. These results are consistent with the findings from previously published GreenGene F™ studies.

Long-term course of anti-factor VIII antibody in patients with hemophilia A at a single center

BACKGROUND: Immune tolerance induction (ITI) can reduce inhibitors against factor VIII concentrates by 70-80%. In this study, we elucidated the characteristics of inhibitors and attempted to determine the proper indications and timing for ITI. METHODS: Subjects included hemophilia A patients registered at the Korea Hemophilia Foundation from 1991 through 2014. Inhibitors were classified as persistent and transient. Patients were classified into groups according to peak inhibitor titer: low (<2 BU/mL), moderate (2 to <5 BU/mL), high (5 to <10 BU/mL), and very high titer (≥10 BU/mL). RESULTS: Overall, 350 (21.4%) of 1,634 hemophilia A patients developed inhibitors at least once. Of these, 100 (6.1%) and 250 (15.3%) patients developed persistent and transient inhibitors, respectively. For transient inhibitors, the median peak titer was 1.0 BU/mL, persistent for median of 11.0 months (10.0, 8.0, 13.0, and 19.0 months in the low, moderate, high, and very high titer transient inhibitor groups, respectively). Overall, 95.8% (215), 72.2% (17), 52.4% (21), and 21.7% (97) of patients in the low, moderate, high, and very high titer groups became inhibitor-negative spontaneously, without ITI. CONCLUSION: Given the spontaneous disappearance of inhibitors and high cost of ITI, it is worthwhile to postpone ITI for 11 months unless the peak inhibitor titer is greater than 10 BU/mL.

Immune tolerance induction in patients with severe hemophilia A with inhibitors

BACKGROUND: Inhibitory antibodies to factor VIII (FVIII) are an important complication when managing patients with hemophilia A. Immune tolerance induction (ITI) has been regarded as a useful method for eradicating inhibitors. We report the results of a retrospective study in Korean patients with hemophilia A who underwent ITI. METHODS: We reviewed the records of patients with hemophilia A with inhibitors who underwent ITI from March 2004 to December 2014. ITI was started with FVIII concentrates at 100 IU/kg, 3 times per week. The dose of FVIII was reduced according to the inhibitor titer and recovery of FVIII. Inhibitor elimination was defined as the time taken to achieve a negative inhibitor assay with no anamnestic response and normal FVIII recovery and/or normal half-life. RESULTS: In total, 17 patients with severe hemophilia A were evaluated. Complete tolerance was achieved in 14 of 17 patients (83%). The mean peak inhibitor titer before ITI was 38.4 BU/mL. The mean treatment duration was 26.2 months. The mean duration between inhibitor detection and ITI was 5.1 years in the complete tolerance group and 10.8 years in the partial tolerance and failed group. CONCLUSION: This study shows that ITI can be an effective and well-tolerated method for eradicating inhibitors. Possible influencing factors for ITI success were age at the start of ITI treatment and duration after inhibitor detection. More research to provide further insight about other factors and conditions is needed.

The Efficacy of Prophylaxis for Children with Severe Hemophilia in Korea - An Experience of Single Institute / 임상소아혈액종양

BACKGROUND: While primary prophylaxis is a well-established and recommended treatment for children with severe hemophilia, there has not been Korean own data. The aim of this study is to lay the foundation for the optimal and available management of hemophilia in Korea.METHODS: We reviewed the medical records of the patients treated with regular factor VIII concentrates infusion as long term continuous treatment at Seoul Clinic of Korea Hemophilia Foundation since August, 2004, retrospectively. We analyzed the efficacy of prophylaxis with the frequency of joint bleed and clinically meaningful bleeding episodes. We also assessed the cost of primary prophylaxis, secondary prophylaxis and on-demand therapy by the factor concentrates consumption.RESULTS: The data from 65 patients were available to evaluate. Of 65 patients, 22 were treated with primary prophylaxis, and 43 with secondary prophylaxis. In the primary and secondary prophylaxis groups, there were 1.9 joint bleeds and 3.3 other bleeding episodes, 7.2 and 9.0, respectively. The mean consumption of factor concentrates per person for primary prophylaxis, secondary prophylaxis and on-demand therapy groups were 2,658.8 IU/kg/year, 2,665.1 IU/kg/year, and 1,271.9 IU/kg/year respectively.CONCLUSION: Now prophylaxis is the recommended treatment for severe hemophilia patients, we should manage our hemophilia patients with standard treatment. And the optimizing treatment regimen for each individual will be needed to establish by studies of individual pharmacokinetics and bleeding tendency.

Measurement of FVIII:C Level by Clot Waveform Analysis / 임상소아혈액종양

BACKGROUND: By using ACL 9000 coagulation analyzer (Instrumentation Laboratory Co., Lexington, Massachusetts, USA), we tried to investigate the possibility that activated partial thromboplastin time (aPTT) clot waveform analysis (CWA) may provide additional information on patients with hemophilia A.METHODS: Plasma samples were obtained from 35 patients with hemophilia A. The factor VIII levels of those patients were measured by a conventional one-stage factor VIII:C clotting assay and a factor VIII antigen assay. The data were applied to a Microsoft excel program calculating the index of the second derivative, and the time at point b (Min2), the point in time that clotting is initiated was also calculated.RESULTS: The corresponding aPTT clotting times were prolonged in all 9 patients with severe hemophilia A. The CWA could further discriminate between different levels of FVIII:C in the patients (n=20), with a FVIII:C level <4 IU/dL by conventional assay. The correlation between FVIII:C and the recalculated aPTT using Min2 was very high in patients with FVIII:C < or =4 IU/dL (r=0.952). Among the 9 patients who showed a lot of discrepancy from the FVIII:C level, there was 8 patients with mild hemophilia and 1 patient with moderate hemophilia (FVIII:C level 4.5%).CONCLUSION: Our study suggested that CWA and Min2 values might have greater discriminatory power in assessing low clotting factor activity. Further study is needed, including more patients with hemophilia A using CWA, correlation according to the severity group, a lower limit of detection for VIII:C, and a multiple one-stage assay.

The Efficacy of Prophylaxis for Children with Severe Hemophilia in Korea - An Experience of Single Institute / 임상소아혈액종양

BACKGROUND: While primary prophylaxis is a well-established and recommended treatment for children with severe hemophilia, there has not been Korean own data. The aim of this study is to lay the foundation for the optimal and available management of hemophilia in Korea. METHODS: We reviewed the medical records of the patients treated with regular factor VIII concentrates infusion as long term continuous treatment at Seoul Clinic of Korea Hemophilia Foundation since August, 2004, retrospectively. We analyzed the efficacy of prophylaxis with the frequency of joint bleed and clinically meaningful bleeding episodes. We also assessed the cost of primary prophylaxis, secondary prophylaxis and on-demand therapy by the factor concentrates consumption. RESULTS: The data from 65 patients were available to evaluate. Of 65 patients, 22 were treated with primary prophylaxis, and 43 with secondary prophylaxis. In the primary and secondary prophylaxis groups, there were 1.9 joint bleeds and 3.3 other bleeding episodes, 7.2 and 9.0, respectively. The mean consumption of factor concentrates per person for primary prophylaxis, secondary prophylaxis and on-demand therapy groups were 2,658.8 IU/kg/year, 2,665.1 IU/kg/year, and 1,271.9 IU/kg/year respectively. CONCLUSION: Now prophylaxis is the recommended treatment for severe hemophilia patients, we should manage our hemophilia patients with standard treatment. And the optimizing treatment regimen for each individual will be needed to establish by studies of individual pharmacokinetics and bleeding tendency.

Measurement of FVIII:C Level by Clot Waveform Analysis / 임상소아혈액종양

BACKGROUND: By using ACL 9000 coagulation analyzer (Instrumentation Laboratory Co., Lexington, Massachusetts, USA), we tried to investigate the possibility that activated partial thromboplastin time (aPTT) clot waveform analysis (CWA) may provide additional information on patients with hemophilia A. METHODS: Plasma samples were obtained from 35 patients with hemophilia A. The factor VIII levels of those patients were measured by a conventional one-stage factor VIII:C clotting assay and a factor VIII antigen assay. The data were applied to a Microsoft excel program calculating the index of the second derivative, and the time at point b (Min2), the point in time that clotting is initiated was also calculated. RESULTS: The corresponding aPTT clotting times were prolonged in all 9 patients with severe hemophilia A. The CWA could further discriminate between different levels of FVIII:C in the patients (n=20), with a FVIII:C level <4 IU/dL by conventional assay. The correlation between FVIII:C and the recalculated aPTT using Min2 was very high in patients with FVIII:C < or =4 IU/dL (r=0.952). Among the 9 patients who showed a lot of discrepancy from the FVIII:C level, there was 8 patients with mild hemophilia and 1 patient with moderate hemophilia (FVIII:C level 4.5%). CONCLUSION: Our study suggested that CWA and Min2 values might have greater discriminatory power in assessing low clotting factor activity. Further study is needed, including more patients with hemophilia A using CWA, correlation according to the severity group, a lower limit of detection for VIII:C, and a multiple one-stage assay.

Efficacy of Tandem High-Dose Chemotherapy and Autologous Stem Cell Rescue in Patients Over 1 Year of Age with Stage 4 Neuroblastoma: The Korean Society of Pediatric Hematology-Oncology Experience Over 6 Years (2000-2005)

The efficacy of tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) was investigated in patients with high-risk neuroblastoma. Patients over 1 yr of age who were newly diagnosed with stage 4 neuroblastoma from January 2000 to December 2005 were enrolled in The Korean Society of Pediatric Hematology-Oncology registry. All patients who were assigned to receive HDCT/ASCR at diagnosis were retrospectively analyzed to investigate the efficacy of single or tandem HDCT/ASCR. Seventy and 71 patients were assigned to receive single or tandem HDCT/ASCR at diagnosis. Fifty-seven and 59 patients in the single or tandem HDCT group underwent single or tandem HDCT/ASCR as scheduled. Twenty-four and 38 patients in the single or tandem HDCT group remained event free with a median follow-up of 56 (24-88) months. When the survival rate was analyzed according to intent-to-treat at diagnosis, the probability of the 5-yr event-free survival+/-95% confidence intervals was higher in the tandem HDCT group than in the single HDCT group (51.2+/-12.4% vs. 31.3+/-11.5%, P=0.030). The results of the present study demonstrate that the tandem HDCT/ASCR strategy is significantly better than the single HDCT/ASCR strategy for improved survival in the treatment of high-risk neuroblastoma patients.

Maintenance Therapy with Activated Prothrombin Complex Concentrate (aPCC) for Hemophilia Patients with High Levels of Responding Inhibitors / 대한혈액학회지

BACKGROUND: Eleven percent of severe hemophilia A patients and 5% of severe hemophilia B patients may develop inhibitors. We have conducted aPCC-based maintenance therapy for hemophilia patients with high levels of responding inhibitors and we analyzed the efficacy, safety, the factor consumption and the expense of this treatment, as compared to on-demand therapy. METHODS: Eleven hemophilia patients with high levels of responding inhibitors were eligible for the study. We tried to evaluate the longitudinal bleeding episodes, the inhibitor titers, the X-ray findings, the adverse events and the factor consumption between on-demand therapy and maintenance therapy. The bypassing agent in this study was aPCC having a longer half-life. The dosage was 30~50 U/kg, 3 times a week. RESULTS: The mean follow-up period was 6.8 months for on-demand therapy and 10.6 months for maintenance therapy. The mean dosage of aPCC was 45.2 U/kg. The episodes of hemarthrosis decreased by 61.4% (P=0.003) and other significant bleedings decreased by 45.2% (P=0.109). The inhibitor titers decreased in 7 patients and these increased in 4 patients, but anamnesis took place in only 1 patient. Radiologically, 2 patients improved, 1 patient got worse and 7 patients were stable. Neither adverse signs nor symptoms were noticed. The mean factor consumption changed from 55.8x10(3) U for aPCC and 48.6 mg for rFVIIa on-demand therapy to 216x10(3) U for aPCC and 4.8 mg rFVIIa for maintenance therapy. Maintenance therapy cost 67% more than on-demand therapy monthly (P=0.041). CONCLUSION: aPCC-based maintenance therapy for hemophilia patients with high responding inhibitors cost 67% more than on-demand therapy, but it reduced by 61.4% the episodes of hemarthrosis and 45.2% of the other significant bleedings. aPCC-based maintenance therapy can very effectively reduce the bleeding episodes of hemophilia patients with high levels of responding inhibitors.

General Principles of Pediatric Oncologic Management / 소아과

No abstract available.

Epidemiology and Clinical Outcomes in Children with Aplastic Anemia in Korea: Retrospective Study / 대한소아혈액종양학회지

PURPOSE: The annual incidence of aplastic anemia (AA) in Asian countries is higher than in Western countries. The pathogenesis in AA has been investigated in hematopoiesis and immunology. Recently, the survival rate and the quality of life of the patients with AA have been steadily improved by the development of a variety of treatments such as the immunosuppressive therapy (IST), and hematopoietic stem cell transplantation (HSCT). The Korean Society of Pediatric Hematology-oncology retrospectively investigated the incidence, treatment strategies, survival rate, and time to become independent from transfusion in patients with AA, who were diagnosed from January 1st, 1991 to December 31st, 2000 in Korea. METHODS: All the questionnaires were sent to a group of training hospitals, and we collected about 600 questionnaire forms from 27 hospitals. However, 493 reports were available for data analysis. RESULTS: The male and female ratio in AA is 1.1 (259 males vs. 234 female). The median age at diagnosis is 9 years old (range; 0.8~16 years old). The annual incidence of children with AA in Korea is 4.5 per million on the basis of Korean pediatric population. In etiology, there are 20 cases (4.1%) in congenital and others in acquired AA. In acquired AA, the cause of illness was not identifiable for most of the patients, but 1 patient had hepatitis-associated AA, and 3 patients developed the illness after medication. According to the initial laboratory data at diagnosis, the peripheral blood findings showed that hemoglobin is 7.1+/-2.4 g/dL, white blood cell 3, 200/microL (200~16, 550), absolute neutrophil counts 670/microL (0~12, 487), platelets 19, 000/microL (1, 000~500, 000), and corrected reticulocytes 0.18% (0.0~4.7). The bone marrow examination revealed that cellularity was below 25% in 348 patients, and over 25% in 105 patients. In the available data, 269 patients (54.6%) were diagnosed of severe aplastic anemia (SAA) and 224 patients of non-SAA (NSAA). HSCT were done for 96 patients (19.5%) and others received another treatments such as the IST. The anti-thymocyte globulin (ATG) or anti-lymphocyte globulin (ALG) treatment was done for 263 cases, corticosteroids for 259, cyclosporine A (CSA) for 215, and anabolic steroids for 138. The combination IST including ATG or ALG plus corticosteroid plus CSA were applied to 154 children with AA, and transfusion only in 37, as conservative care. In case of those patients with HSCT, the time from diagnosis to transplantation was 12 months (1~144 months) and the sources of stem cells were bone marrow in 82 cases, growth factor mobilized peripheral blood in five, and cord blood in six. There were 57 patients transfused below 40 units of blood products before HSC transplantation. Graft rejection was identified from 16 patients, and booster transplantations were done for 12 patients among them. In complications of HSCT, the graft versus host disease was developed in 20 patients and viral diseases in 12 cases including the CMV, herpetic infection, and hepatitis. Also, one patient suffered from veno-occlusive disease. The overall survival rate in children with AA is 64.3%. The survival rate in HSCT is better than that IST (76.9% vs. 62.6%, P< 0.05). In IST, overall survival rate in very SAA showed lower than SAA and NSAA, and in SAA lower than NSAA in case of absolute neutrophil count below 200/microL (P< 0.05). There was no significant difference in terms of the sex, age at beginning of treatment. In HSCT, transfusion was not related to the survival rate. However, overall survival rate is better in short interval between diagnosis and HSCT than in long interval (P< 0.05). There was no significant difference in the probability of transfusion independence according to treatment strategies, even though it was 71.0% in HSCT and 12.8% in immunosuppressive therapy at the end point of survey (P=0.47). The response pattern was as follows. There were 155 cases of complete response, 110 of partial response and 120 of no response in spite of various treatments. The relapse after treatment was found in 11 patients after IST, of which 6 patients experienced more than 2nd relapse. The median time between the end of treatment and relapse was 16 months (6~84 months). Only three cases developed into other diseases (1 case into acute myeloid leukemia and 2 cases into myelodysplastic syndrome). The median time from diagnosis to the end of treatment was 62 months (0.5~174 months). In fatal cases, the median time between diagnosis and death was 29 months (0~144 months) despite several therapeutic strategies. CONCLUSION: In Korea, the annual incidence of children with AA is 4.5 per million. This result is similar to the ones reported in other Asian countries, but higher than those in Western countries. Although a lot of children with AA received various therapies including IST or HSCT, new treatment strategies have to be developed to improve the survival rate and the quality of life of children with AA

Epidemiology and Clinical Outcomes in Children with Malignant Lymphoma in Korea: Retrospective Study / 대한소아혈액종양학회지

PURPOSE: Malignant lymphoma is the primary malignant tumor derived from lymphoid organs. It is composed of Hodgkin's disease and non-Hodgkin lymphoma. Recently, survival rate is on the rise due to improved combination chemotherapy, radiotherapy and high dose chemotherapy followed by hematopoietic stem cell transplantation. In South Korea, no epidemiologic studies concerning malignant lymphoma in the pediatric age group has been performed. Therefore, the Korean Society of Pediatric Hematology-Oncology retrospectively analyzed the incidence, pathologic subtypes, treatment strategies, and survival rates of pediatric malignant lymphomas in South Korea. METHOD: Questionnaires were made and sent to a group of training hospitals, with a return of 580 questionnaires from 24 hospitals. Among them, 517 reports were suitable for analysis. RESULTS: Among the 517 cases, Hodgkin's disease accounted for 58 cases and non-Hodgkin's lymphoma for 459 cases. Male to female ratio for malignant lymphoma was 2.7. Mean age at diagnosis was 8.3 years. Among the pathologic subtypes, mixed cellularity was the most frequent subtype for Hodgkin's disease. Most (70.7%) cases of non-Hodgkins lymphoma belonged to high grade NHL. Burkitt lymphoma accounted for 102 cases, and lymphoblastic lymphoma was found in 58 cases. Peripheral lymphadenopathy was the most common presenting sign upon diagnosis. B symptoms were significantly more frequent in Hodgkin's disease patients than in non-Hodgkin lymphoma patients. The Complete response rate was 62.1% for non-Hodgkin's lymphoma, and 82.8% for Hodgkin's disease. Overall 5 year survival rate was 60.0% in non-hodgkin's lymphoma, and 84.8% in Hodgkin's disease. CONCLUSION: The annual incidence of malignant lymphoma in Korea is 4.7 per million. In cases of chemotherapy-sensitive, refractory or relapsed malinant lymphoma, high dose chemotherapy followed by hematopoietic stem cell transplantation is vital for improved survival. For more systematic analysis of epidemiology on malignant lymphomas, better surveillance mechanisms on the occurrence of malignant lymphomas are crucial, and establishment of standardized treatment protocol for malignant lymphoma is required.

Epidemiology and Clinical Outcomes of Childhood Wilms Tumor in Korea / 대한소아혈액종양학회지

PURPOSE: Wilms tumor is the most common malignant renal tumor in children. We investigated the epidemiology, clinical features and treatment outcome of the children with Wilms tumor in Korea during the recent 10 years. METHODS: Two hundred forty six patients were enrolled between January 1991 and December 2000 from 26 major hospitals in Korea. The data regarding the clinical features including sex, age, pathologic type, prognostic factor and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed, The differences between groups were analyzed by log-rank test. RESULTS: There were 130 males and 116 females. The incidence between the age of 1~4 years was the highest with 66.2%. The annual incidence rate per 1, 000, 000 population varied from 1.9 to 2.1. The 10 years overall survival rate according to sex, clinical stage, pathologic type and relapse were as follows: 88.6% in male, 90.9% in female, 100% in stage I, 94.7% in stage II, 92.1% in stage III, 63.4% in stage IV, 85.7% in stage V, 95.3% in favorable histology, 64.1% in unfavorable histology, 94.8% in non-relapse, and 40.9% in relapse. The relapse rate was 12%. The 10 years overall survival rate of 246 patients were 89.1%. CONCLUSION: Our results could provide the most recent and important clinical information on Wilms tumor of children in Korea.

A Case of Hemolytic Disease in a Newborn Due to Anti-Jk(b)

The isoimmune hemolytic disease of newborn due to the incompatibility of minor blood groups is characterized by progressive neonatal hyperbilirubinemia and anemia caused by the IgG antibody transmitted from the mother to the fetus. Recently we had a case of hemolytic disease in a newborn due to anti-Jk(b). There were no ABO and Rh(D) incompatibilities between mother and baby. The infant's direct and indirect antiglobulin tests were strongly positive. From the mother and baby, an irregular antibody was found and identified as anti-Jkb. Generally, hemolytic disease of the newborn resulting from anti-Jkb incompatibility has a benign clinical course and a good prognosis. This patient completely recovered without exchange transfusion. We report this case with a brief review of relevant literature.

A Case of Neonatal Tetanus Cured with Neuromuscular Blocking Agent and Ventilatory Support

A neonate born at 38 gestational weeks was admitted due to generalized tonic-clonic seizure and cyanosis. The neonate was born six days previously at home through normal delivery and the umbilical cord was cut using scissors sterilized in boiling water. The neonate weighed 3,180 g at admission. Physical examination revealed cyanosis, opisthotonus, trismus and reactive muscle spasms. Laboratory exam, brain sonogram and EEG showed no significant abnormal findings. Based on her history and physical examination, the neonate was diagnosed with tetanus and put in an incubator isolated in a quiet, dark room. Treatment with tetanus human immunoglobulin along with antibiotics (penicillin G) were started immediately, and mechanical ventilation, administration of neuromuscular blocking agent and muscle relaxant were also started off. The frequency of seizure episode decreased gradually, and on the 32nd hospital day, mechanical ventilatory support was stopped along with extubation two days later. Thereafter, the neonate was in continuous generalized hypertonic state and showed feeding difficulty, but there was gradual improvement. She was dismissed on the 49th hospital day and is currently under OPD follow-up, doing well with no special problems. Respiratory management is critical to neonatal tetanus. We report here a case of tetanus treated with inhibition of self-respiration, neuromuscular blocker and application of ventilator, and present this method as a useful direction for future treatment of neonatal tetanus.

Comparison of Clinical Courses According to the Existence of Patent Ductus Arteriosus in Respiratory Distress Syndrome

PURPOSE: To compare perinatal characteristics, clinical courses, and overall morbidity between respiratory distress syndrome(RDS) with patent ductus arteriosus(PDA) and RDS without PDA in neonates. METHODS: Eighty-three neonates who were diagnosed and treated for RDS in the neonatal intensive care unit(NICU) from Jan. 2000 to Dec. 2002 were included in this study. RDS was complicated with PDA(group A) in 17 patients and not complicated in 66(group B). PDA was diagnosed by echocardiogram in neonates with congestive heart failure symptom, cardiac murmur or chest X-ray findings of cardiomegaly or pulmonary edema. A retrospective study was undertaken of the perinatal charac teristics and overall morbidity in group A and group B. RESULTS: The birth weight and gestational periods of group A were less compared with group B. There was more perinatal asphyxia in group A. Incidence of overall morbidity such as bronchopul monary dysplasia, intraventricular hemorrhage and death was higher in group A. Intravenous indomethacin was administered in 17 PDA infants. CONCLUSION: The perinatal characteristics in the two groups showed a significant difference. Incidence of overall morbidity in the two groups showed significant differences, however, there is no simple conclusion to draw because we didn't do multifactorial analyses to rule out other many risk factors affecting morbidity, such as gestational weeks or birth weight.

Postnatal Outcome of Neonatal Thyroid Function Born to Mother with Thyroid Dysfunction / 대한주산의학회잡지

OBJECTIVE: The health of the mother during pregnancy has a great effect on the fetus and the neonate. This research was conducted to determine what effect thyroid disease control and administration of medication during pregnancy had on the thyroid function of the newborn. METHODS: Clinical observation was conducted by examining the history, medical records, and neonatal thyroid function tests and records of 79 infants born to 79 mothers with thyroid dysfunction in the OBGY department at the Kyung Hee Medical Center between January of 1995 to December of 2000. RESULTS: Of the 79 research subjects, 55 infants were born to mother with hyperthyroidism(Group A)(70%), and 24 infants were born to mother with hypothyroidism(Group B)(30%). Infants born to mothers maintained normal thyroid function during pregnancy(Group I) are 52 cases(66%), undetermined state(Group II) are 16 cases(20%), and thyroid dysfunction(Group III) are 11 cases(14%). The accompanying diseases were demonstrated. There were no difference in clinical characteristics of the infants between Group A and Group B. 5 infants in Group 1(9%), 7 infants in Group 2(Group 43%), 9 infants in Group 3(82%) demonstrated thyroid dysfunction. 76% of the neonates with thyroid dysfunction were born from mothers with a history of intake of medication(Table 4). Of the total of 79 infants born to mothers with thyroid dysfunction, only 1 neonate developed hyperthyroidism and others returned to normal thyroid function. CONCLUSION: Through this research, we were able to learn that in mothers with thyroid dysfunction during pregnancy the level of control of thyroid function and the intake of medication has significantly effect on the neonate.

A Case of Idiopathic Neonatal Chylothorax

Chylothorax is the most common cause of pleural effusion in the neonatal period and is defined as an effusion of lymph in the pleural cavity. We report a case of chylothorax in 8-day-old male who was admitted due to respiratory difficulty. Chest AP roentgenogram showed pleural effusion of the left lung, and milky yellow fluid was aspirated via thoracentesis. Diagnosis was confirmed by chemistry studies of pleural lipid and lipoprotein electrophoresis. Chyle obtained from pleural space was diagnosed by their high triglyceride levels and the finding of chylomicrons on lipid electrophoresis. He was treated by thoracentesis, chest tube insertion, feeding with formulas containing medium-chain triglyceride and total parenteral nutrition without oral feeding. He was discharged on the 45th hospital day in good health.