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.

BACKGROUND: This study aimed to survey the clinical spectrum of diffuse large B-cell lymphoma (DLBCL) in terms of epidemiology, pathologic subtypes, stage, and prognostic index as well as treatment outcomes. METHODS: In 2007-2008, 13 university hospitals evenly distributed in the Korean peninsula contributed to the online registry of DLBCL at www.lymphoma.or.kr and filed a total of 1,665 cases of DLBCL recorded since 1990. RESULTS: Our analysis showed a higher prevalence of DLBCL in male than in female individuals (M:F=958:707), and extranodal disease was more common than primary nodular disease (53% vs. 47%). Among the 1,544 patients who had been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or rituximab-CHOP (R-CHOP) therapy with or without radiation, 993 (63.9%) were alive, with 80% free of disease, 417 were dead (26.8%), with 13% free of disease, and 144 (9.3%) were lost to follow-up, with 23% free of disease. Age below 60 years, stage at diagnosis, international prognostic index (IPI) score regardless of age, and addition of rituximab to CHOP therapy in low- and low-intermediate-risk groups according to IPI scores significantly increased survival duration. CONCLUSION: The epidemiology, clinical spectrum, and biological behavior of DLBCL in Korea are similar to those observed in Western countries, and the advent of rituximab improved survival.
Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Combined Chemotherapy Protocols ; B-Lymphocytes ; Cyclophosphamide ; Doxorubicin ; Female ; Hospitals, University ; Humans ; Korea ; Lost to Follow-Up ; Lymphoma ; Lymphoma, B-Cell ; Male ; Prednisolone ; Prevalence ; Vincristine ; Rituximab

Although uncommon, acquired hemophilia A (HA) is associated with a high rate of mortality due to severe bleeding. In spite of many hypotheses regarding the cause of acquired HA, there is as yet no established theory. In this study, we investigated the possibility that mutation(s) in the F8 gene may be correlated with the development of inhibitory autoantibodies. Direct sequencing analysis was performed on all 26 exons of the F8 gene of 2 patients exhibiting acquired HA. Both patients were found to share a common point mutation (c.8899G>A) in the 3'-untranslated region (3'-UTR) of exon 26. This is the first report on the genotyping of F8 in the context of acquired HA.
Autoantibodies ; Exons ; Hemophilia A ; Hemorrhage ; Humans ; Point Mutation

Dermatomyositis (DM) is a rare and idiopathic inflammatory myopathy with characteristic cutaneous manifestations. There is a well-recognized association between DM and cancers. In Korea, several DM cases have been reported to be associated with stomach cancer, breast cancer, acute lymphoblastic leukemia, lung cancer, and tonsil cancer. However, an association between DM and lymphoma in Korea has not been reported up to now. We report a case of DM who developed diffuse large B-cell lymphoma 1 year and 8 months later.
Breast Neoplasms ; Dermatomyositis ; Korea ; Lung Neoplasms ; Lymphoma ; Lymphoma, B-Cell ; Myositis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Stomach Neoplasms ; Tonsillar Neoplasms

Many AML-associated chromosomal abnormalities, such as t(8;21), t(15;17), inv(16), t(9;11), t(9;22) and t(6;9) are well known. The chromosomal aberration of t(16;21)(p11;q22) in AML is rare and it is known to be associated with poor prognosis, young age (median age, 22 yr), and involvement of various subtypes of the French-American-British classification. We report here 2 AML patients with t(16;21)(p11;q22), proved by conventional cytogenetics and/or reverse transcription (RT)-PCR. Erythrophagocytosis by leukemic blasts was observed in both of the cases. One patient was a 24 yr-old male with acute myelomonocytic leukemia. His karyotype was 46,XY,t(16;21)(p11;q22),del(18)(p11.2) and RT-PCR revealed the TLS/FUS-ERG fusion transcripts. Although he received allogeneic peripheral blood stem cell transplantation after the first remission, he died 9 months after the initial diagnosis due to relapse of the disease and graft-versus-host disease. The other patient was a 72 yr-old male with acute myeloid leukemia without maturation. His karyotype was 45,XY,-16,add(21)(q22) and the presence of t(16;21)(p11;q22) was detected by RT-PCR. He was transferred to another hospital with no more follow-up. We suggest that the presence of t(16;21)(p11;q22) and/or TLS/FUS-ERG fusion transcripts has to be considered in cases of AML with erythrophagocytosis.
Aged ; Chromosomes, Human, Pair 16/*genetics ; Chromosomes, Human, Pair 22/*genetics ; Graft vs Host Disease/diagnosis ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute/diagnosis/*genetics ; Male ; Oncogene Proteins, Fusion/*genetics ; RNA-Binding Protein FUS/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; *Translocation, Genetic ; Young Adult

BACKGROUND: On performing umbilical cord blood (UCB) transplantation, faster engraftment may lead better clinical outcome. Because transplanted viable cell count in UCB is related to the engraftment, accurate evaluation of viability of CD34+cells in cryopreserved UCB has clinical implication. We examined the difference in viability of cells in cryopreserved UCB according to the duration of cryopreservation and different methods. METHODS: A total of 60 UCB samples which were cryopreserved for 1 to 4 years were used in this study. Viability of cryopreserved cells were examined with trypan blue exclusion assay, DNA contents analysis, caspase-3 activation test, intracellular esterase activity and Annexin-V/PI staining. RESULTS: After thawing the cryopreserved UCB, 89% of the total MNCs and 84% of CD34+cells were viable as identified by trypan blue exclusion assay. In the CD34+cell population, the cell death rate was found to be 47% by Annexin-V/PI staining and less than 5% by DNA contents analysis. However, cspase-3 activity failed to document apoptosis. The intracellular esterase activity test also showed a cell death rate of about 10~20% at 2, 4, and 6 hours after thawing. CONCLUSION: Viable cells in UCB should be measured by several compensatory techniques rather than a single method. Discordance among Annexin-V/PI staining versus trypan blue exclusion, DNA contents analysis, and the caspase-3 activation test or intracellular esterase activity should be clarified in order to apply these techniques for actual cord blood transplantation.
Apoptosis ; Caspase 3 ; Cell Count ; Cell Death ; Cryopreservation ; Diminazene ; DNA ; Fetal Blood ; Transplants ; Trypan Blue

BACKGROUND: Acute leukemias co-expressing myeloid and lymphoid antigens but does not meet the criteria for biphenotypic acute leukemia (BAL) is common, however its clinical significance is not fully defined. METHODS: In this study, clinical features of 68 co-expressing (myeloid and lymphoid) acute leukemias diagnosed between January 2000 and December 2006 were studied and compared with those of a control group of patients (pure AML or ALL). RESULTS: Age, gender, initial Lactate dehydrogenase (LDH) level and cytogenetics were not different between the co-expressing group and the control group. But, the initial bone marrow blast percent was significantly higher in the co-expressing group (70% vs. 54.5%, P=0.003). Fifty five percent (16/29) of ALL and 30% (52/172) of AML patients showed myeloid and lymphoid markers concomitantly. The lymphoid antigen positive AML (Ly+AML) patients showed significantly shorter survival rates than pure AML patients (4 year survival rate, 17.6% vs. 45.6%, P=0.002). However hematopoietic stem cell transplantation (HST) abrogated the difference (4 year survival rate, 54.7% vs. 50.6%, P=0.894). In ALL patients, survival rate was not affected by myeloid antigen co-expression (4 year survival rate 26.1% vs. 20%, P=0.954). CONCLUSION: Co-expression of lymphoid markers in AML should be regarded as a poor prognostic factor and more aggressive treatment such as HST should be considered.
Bone Marrow ; Cytogenetics ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunophenotyping ; L-Lactate Dehydrogenase ; Leukemia ; Leukemia, Biphenotypic, Acute ; Prognosis ; Survival Rate

BALT(bronchial associated lymphoid tissue) lymphomas are a distinct subgroup of low-grade B-cell extranodal non-Hodgkin's lymphoma, which are classified as a marginal-zone lymphomas. The majority of the patients are asymptomatic or their pulmonary lesions is often discovered incidentally on a routine chest radiograph. A 50-year-old man was admitted for an the evaluation of cough, dyspnea and fever. His chest CT showed ground glass appearance with interlobular septal thickening in both lower lobes, right middle lobe and left lingular division. He had been initially diagnosed with lipoid pneumonia and was kept under observation. However, his chest lesion showed continuous progression and a video-associated thoracoscopy was performed His pulmonary lesion was confirmed histologically to be a BALT(bronchial associated lymphoid tissue) lymphoma. We report a case of a BALT lymphoma, which was initially misdiagnosed as lipoid pneumonia.
B-Lymphocytes* ; Cough ; Dyspnea ; Fever ; Glass ; Humans ; Lymphoid Tissue* ; Lymphoma ; Lymphoma, B-Cell* ; Lymphoma, Non-Hodgkin ; Middle Aged ; Pneumonia* ; Radiography, Thoracic ; Thoracoscopy ; Thorax ; Tomography, X-Ray Computed

BALT(bronchial associated lymphoid tissue) lymphomas are a distinct subgroup of low-grade B-cell extranodal non-Hodgkin's lymphoma, which are classified as a marginal-zone lymphomas. The majority of the patients are asymptomatic or their pulmonary lesions is often discovered incidentally on a routine chest radiograph. A 50-year-old man was admitted for an the evaluation of cough, dyspnea and fever. His chest CT showed ground glass appearance with interlobular septal thickening in both lower lobes, right middle lobe and left lingular division. He had been initially diagnosed with lipoid pneumonia and was kept under observation. However, his chest lesion showed continuous progression and a video-associated thoracoscopy was performed His pulmonary lesion was confirmed histologically to be a BALT(bronchial associated lymphoid tissue) lymphoma. We report a case of a BALT lymphoma, which was initially misdiagnosed as lipoid pneumonia.
B-Lymphocytes* ; Cough ; Dyspnea ; Fever ; Glass ; Humans ; Lymphoid Tissue* ; Lymphoma ; Lymphoma, B-Cell* ; Lymphoma, Non-Hodgkin ; Middle Aged ; Pneumonia* ; Radiography, Thoracic ; Thoracoscopy ; Thorax ; Tomography, X-Ray Computed

BACKGROUND: It is still obscure how dendritic cells (DCs) can orchestrate whole immune reactions according to the host age. We studied changes of murine splenic DCs after total body irradiation (TBI), with regards to age. METHODS: Young (8~14 wk) and old (12~16 mo) C57Bl/6 mice were irradiated with a dose of 1,100 cGy and were assessed 6 h later for phenotypic and functional changes of the DCs. The mean fluorescence intensities and cytokine producing cell proportions were analyzed with the student's t-test. RESULTS: Interleukin-12 (IL-12), interferon (IFN gamma) and tumor necrosis factor (TNF alpha) producing classical DCs (cDCs) were more numerous in the young untreated mice than in the old mice. However, the number of these cells decreased in the young mice and increased in the old mice after TBI. IL-12, IFN gamma and TNF alpha producing plasmacytoid DCs (pDCs) were more frequent in the old mice than in the young mice before TBI both mice showed an increased frequency of cells producing these cytokines after TBI. Overall, the highest numbers of cDCs and pDCs producing IL-12, IFN gamma and TNF alpha were present in the old mice after TBI. In both the cDC and pDC populations, the old mice had a higher frequency of IL-10+ cells prior to TBI. After irradiation, the young mice had a higher frequency of IL-10+ cells. CONCLUSION: With TBI, the DCs showed dramatic differences between young and old mice. Young mice turned to an immuno-suppressive response whereas the old mice changed to an immuno-stimulation of DCs after TBI. From these dramatic aging effects, we hope to explain the different frequencies and severities of acute GvHD after allogeneic hematopoietic stem cell transplantation according to host age.
Aging* ; Animals ; Centers for Disease Control and Prevention (U.S.) ; Cytokines ; Dendritic Cells* ; Fluorescence ; Hematopoietic Stem Cell Transplantation ; Hope ; Interferons ; Interleukin-12 ; Mice* ; Tumor Necrosis Factor-alpha ; Whole-Body Irradiation*