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  • American Society of Hematology  (17)
  • 1
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 5157-5157
    Abstract: Abstract 5157 Background: With the development of diagnostic technique, an accurate diagnosis of hereditary hemolytic anemia (HHA)- red blood cell (RBC) membranopathy, hemoglobinopathy, RBC enzymopahty – have been made. Therefore, we surveyed the prevalence and characteristics of patients diagnosed as HHA during recent five years in Korea. Methods: Through the use of questionnaires, information on the clinical and laboratory findings of HHA diagnosed from 2007 to 2011 in Korea was collected. The globin gene analysis (direct sequencing) and RBC enzyme analysis was performed at the representative laboratories. A total of 203 cases were collected in this study by the Korean Hereditary Hemolytic Anemia Working Party of the Korean Society of Hematology. Results: Patients number of RBC membranopathy, hemoglobinopathy, and RBC enzymopahty was 125, 47, and 31, respectively. Percentage of patients with dominant family history was 57% in patients with hereditary spherocytosis (n=116) and dominant symptoms were anemia, jaundice, splenomegaly and gallstones. Osmotic fragility test and flow cytometric method for detection of RBC membrane defect were performed about 60% of patients. RBC membrane protein analysis using sodium dodecyl sulfate polyacrylamide gel electrophoresis was performed on 59 patients. Of the 47 cases of hemoglobinopathies, 36 cases (77%) were β-thalassemia minor, 10 cases (21%) were α-thalassemia minor and one case (2%) was unstable Hb, Hb M-Saskatoon (beta 64 His-→Tyr). Median age at diagnosis was 7 years (range: 6 months–58 years). Eleven of 47 cases (23%) had family history of HHA. As all thalassemia patients were thalassemia minor, they presented with mild jaundice or pallor. Of the 31 patients were diagnosed as RBC membranopathy, pyruvate kinase deficiency was 3 cases and glucose-6 phosphate dehydrogenase deficiency was 2, and other various forms were reported. Conclusions: We could confirm that accurate diagnosis has been made in more patients using elegant diagnostic technique. However, more defined diagnostic approaches were needed in this rare disease and further systematic supporting systems for patients and their families were warranted in public health aspect. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1243-1243
    Abstract: Background: Hereditary spherocytosis (HS) is the most common cause of hereditary hemolytic anemia. Current tests used to diagnose HS focus on the detection of hemolysis or indirectly assess protein defects. Direct methods to detect protein defects are complicated and difficult to implement. Recent next-generation sequencing (NGS) methods enable large-scale gene mutation analyses to be used for such diagnoses. In this study, we investigated the patterns of genetic variation associated with HS among the patients diagnosed with HS clinically. Specifically, we analyzed mutations in red blood cell membrane protein-encoding genes (17 genes) in context with 5 genes for the differential diagnosis (thalassemia, congenital dyserythropoietic anemia, paroxysmal nocturnal hemoglobinuria) in Korean HS. Methods: In total, 60 patients diagnosed with HS were enrolled in this study. Targeted sequencing of 43 genes (17 membrane protein-encoding genes, 20 enzyme-encoding genes, and 6 additional candidate genes) was performed using the Illumina HiSeq platform and variants were called according to a data-processing pipeline. Results: Of the 60 patients, 50 (83%) had one or more significant variants in a membrane protein encoding genes. A total of 54 significant variants (8 previously reported and 46 novel) were detected in 6 membrane protein-encoding genes; SPTB, ANK1, SPTA1, SLC4A1, EPB41, and EPB42. The most variants (28/60 patients) were detected in SPTB. Interestingly, concurrent mutations of genes encoding enzymes (ALDOB, GAPDH, and GSR) were detected along with mutations of membrane encoding genes. One patient diagnosed with HS harbored mutation of G6PD without mutation of HS related genes. Additionally, UGT1A1 mutations were present in 5 patients. Positive rate of osmotic fragility test was 86% among patients with HS related gene mutations. Conclusion: These results clarify the molecular genetic analysis is required for the accurate diagnosis of HS. About 17% of patients who were clinically diagnosed as HS revealed discrepancy with molecular diagnosis. Figure Figure. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1932-1932
    Abstract: Abstract 1932 Introduction: The use of micafungin, a member of the novel class of antifungal agents, the echinocandins, in adults has proven to be effective and safe for antifungal prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. However, there are few reports describing its prophylactic use in pediatric patients. The objectives of this study were to evaluate the efficacy and safety of micafungin for the prevention of invasive fungal disease (IFD) in patients undergoing allogeneic HSCT exclusively focusing on children and adolescents. Patients and Methods: This was prospective, multi-center, open-label, single arm study. The study drug, micafungin, was administered intravenously at a dose of 1 mg/kg/day for patients 〈 50 kg and 50 mg/day for patients ≥50 kg from the beginning of conditioning until neutrophil engraftment. Treatment success was defined as the absence of suspected, probable, or proven IFD through the end of 4 weeks after therapy. Clinical and laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Results: From April 2010 to December 2011, 152 patients were enrolled from 10 institutions in Korea, and a total of 144 patients were analyzed. The median age of the patients was 9.5 years (range, 0.4 – 19.8 years). Approximately 94% of patients received myeloablative conditioning regimen. Graft source included bone marrow (11.9%), peripheral blood (82.5%) and cord blood (5.6%). Most commonly, patients received HSCT for treatment of acute myeloid leukemia (27.8%), acute lymphocytic leukemia (27.1%), or severe aplastic anemia (19.4%). The median duration of prophylactic micafungin treatment was 23 days (range, 4 –169 days). Of the 144 patients, 117 patients completed micafungin prophylactic administration until neutrophil engraftment. Eleven patients developed suspected (n=5), possible (n=3), or probable (n=3) IFD. No patients died of IFD at any time during the study. Thirty-eight patients experienced adverse events (AEs) possibly related to micafungin. Only two patients discontinued micafungin prophylaxis due to AEs. Common AEs included hepatotoxicity, gastrointestinal discomfort, electrolyte imbalance and myelosuppression. Conclusions: This study shows the efficacy and safety of micafungin for the prevention of IFD after allogeneic HSCT in children and adolescents. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 138, No. 21 ( 2021-11-25), p. 2117-2128
    Abstract: Shwachman-Diamond syndrome (SDS; OMIM #260400) is caused by variants in SBDS (Shwachman-Bodian-Diamond syndrome gene), which encodes a protein that plays an important role in ribosome assembly. Recent reports suggest that recessive variants in EFL1 are also responsible for SDS. However, the precise genetic mechanism that leads to EFL1-induced SDS remains incompletely understood. Here we present 3 unrelated Korean SDS patients who carry biallelic pathogenic variants in EFL1 with biased allele frequencies, resulting from a bone marrow–specific somatic uniparental disomy in chromosome 15. The recombination events generated cells that were homozygous for the relatively milder variant, allowing for the evasion of catastrophic physiologic consequences. However, the milder EFL1 variant was still solely able to impair 80S ribosome assembly and induce SDS features in cell line and animal models. The loss of EFL1 resulted in a pronounced inhibition of terminal oligopyrimidine element–containing ribosomal protein transcript 80S assembly. Therefore, we propose a more accurate pathogenesis mechanism of EFL1 dysfunction that eventually leads to aberrant translational control and ribosomopathy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3425-3425
    Abstract: Background: The FMS-like tyrosine kinase 3 (FLT3) is mutated in approximately 30% of acute myeloid leukemia (AML) patients either by internal tandem duplication (ITD) or by point mutations in the tyrosine kinase domain (TKD). PHI-101 is a Type I FLT3 inhibitor developed to overcome resistance in AML. PHI-101 showed potent cellular activity in vitro and in vivo for both FLT3 ITD mutations and a wide variety of FLT3 point mutations in TKD. In preclinical studies utilizing primary human FLT3-ITD leukemia cells, PHI-101 showed increased anti-leukemic activity compared to gilteritinib based on increased survival in mice transplanted with these samples. The Phase 1a and Phase 1b global clinical trial with PHI-101 (NCT04842370) is currently underway to assess the overall safety and efficacy of PHI-101 in refractory and relapsed AML. Study Design and Methods: The overall design of the AML clinical trial consists of two parts, phase 1a, the dose-escalation, and phase 1b, the dose-expansion trial utilizing oral PHI-101 tablets. Up to 5 dose levels are planned for phase 1a and a single subject enrolled per dose level until the occurrence of at least one subject with more than Grade 2 toxicity according to CTCAE5.0 criteria during the 28-day evaluation period. The dose escalation will then convert to a standard 3+3 scheme, with 3 to 6 subjects per dose level cohort over the 28-day cycle. If there are no dose-limiting toxicities (DLT), dose escalation to the next higher dose levels will proceed upon the recommendation of the Safety Monitoring Committee. Subjects with FLT3 mutations or FLT3 wild-type will be enrolled in the dose-escalation cohort, and blood samples are collected for the primary endpoint pharmacokinetics (PK) and for the exploratory pharmacodynamic (PD) endpoint evaluation, including plasma inhibitory assay and biomarker analysis. Results: The Phase 1a clinical trial of PHI-101 was initiated in June 2020 at a daily dose of 40mg for level 1. As of July 31, 2021, 8 patients with relapsed or refractory AML have been enrolled in the trial, all of whom had prior anti-leukemic treatments with intensive chemotherapy, hypomethylating agents and/or other FLT3 inhibitors. To date, 5 enrolled patients were available for safety assessment at three dose levels and have not experienced any dose-limiting toxicities (DLTs) from repeating doses of the 28-day DLT-assessment window. The leukemic blasts in marrow or peripheral blood were dramatically reduced by up to 98% with one cycle (28 days). The pharmacokinetic data of plasma PHI-101 varied in a dose-proportional manner and peak plasma concentrations (Cmax) were reached between 4 and 6 hours after once-daily dosing. The pharmacodynamic evaluation by plasma inhibitory assay showed that plasma from patients receiving at daily doses of PHI-101 inhibited more than 90% of the phosphorylation of the FLT3-ITD receptor. PHI-101 was well tolerated with these dose levels. This study is currently recruiting FLT3 mutation or wild-type AML patients at multiple sites in Korea and Australia. Conclusion: PHI-101 is a next-generation FLT3 inhibitor that showed a potent anti-leukemic activity and improved efficacy in primary AML samples harboring FLT3/ITD and FLT3/TKD mutations in preclinical studies. The current analysis of this trial indicated that PHI-101 is a very effective FLT3 inhibitor for both refractory and relapsed AML patients, including those that have relapsed on other FLT3 TKI. The assessments of safety, tolerability, and PK of PHI-101 to determine the recommended dose for expansion are ongoing in the Phase 1a clinical trial. Disclosures Lee: Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board; AbbVie: Honoraria, Other: Advisory board; Korean Society of Hematology: Membership on an entity's Board of Directors or advisory committees. Im: Pharos iBio Co., Ltd.: Current Employment. Nam: Pharos iBio Co., Ltd.: Current holder of individual stocks in a privately-held company. Kim: Pharos iBio Co., Ltd.: Current holder of individual stocks in a privately-held company. Han: Pharos iBio Co., Ltd.: Current holder of individual stocks in a privately-held company. Yoon: Pharos iBio Co., Ltd.: Current holder of individual stocks in a privately-held company. Small: Pharos iBio Co., Ltd.: Consultancy, Other: Scientific Advisory Board. The arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict-of-interest policies, Research Funding; InSilico Medicine: Other: Scientific Advisory Board.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 3365-3366
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 9498-9500
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5981-5981
    Abstract: Introduction Although most of the studies about health related quality of life (HRQoL) focuses on acute leukemia survivors, few studies compared the HRQoL in acute leukemia survivors with that of the general population. The objective of the present study was to evaluate the HRQoL of acute leukemia survivors in a case-control study using The Sixth Korean National Health and Nutrition Examination Survey (KNHANES VI). Method We enrolled 149 acute leukemia survivors from three Korean tertiary care centers from 1983 through 2014. Survivors completed a set of questionnaires which included the EuroQOL five dimensions questionnaire (EQ-5D), the EORTC Quality of Life Core Questionnaire (QLQ-C30), Brief Fatigue Inventory (BFI), Hospital Anxiety and Depression Scale for Korean (HADS-K), Brief Encounter Psychosocial Instrument (BEPSI), Abbreviated Dyadic Adjustment Score (ADAS), and Family APGAR. We identified 447 control subjects matched for age, sex, education status, marital status, and presence of any comorbidity from KNHANES VI database. The scores for EQ-5D and health behaviors regarding rate of smoking, drinking, health medical examination, cancer screening, and vaccination were compared with the general population. Other survey results including EORTC QLQ-C30 were analyzed among the leukemia survivors, to evaluate the impact on QoL of postremission treatment strategy (SCT or chemotherapy). We compared the adjusted QoL mean across groups by analysis of covariance. Result Median age of the study participants was 44 years (range, 16 - 78), and there were 75 men (50%) and 74 women (50%). Majority of the patients had acute myeloid leukemia (n = 121); others had acute lymphoblastic leukemia (n = 24) and acute biphenotypic leukemia (n = 4). Among the survivors, 93 received chemotherapy and 56 received SCT as postremission treatment. Median duration of time between treatment completion and the study survey was 59 months. Examination of each of the five dimensions of the EQ-5D showed that the acute leukemia survivor group was having more difficulties or problems compared with the general population. More than twice as many respondents with leukemia survivors reported having problems with usual activities (14.6% vs. 4.6%, p 〈 0.001), and anxiety or depression (23.6% vs. 9.1%, p 〈 0.001). Furthermore, a significant proportion of patients reported pain compared with their matched population (34.7% vs. 20.3%, p= 0.002). Among the survivors, SCT group had clinically significantly worse problems with role functioning, fatigue, and insomnia than chemotherapy group, measured by the QLQ-C30. SCT group also had statistically significantly worse problems with global health status/QoL, physical and emotional functioning, pain, dyspnea, and appetite loss. Depression was higher in the SCT patients compared with the chemotherapy patients (mean HADS-depression score 4.99 vs. 6.56, p= 0.024). There was no difference in the HADS-anxiety score, BFI, BEPSI, dyadic adjustment and family function between the subgroups. In terms of health behaviors, acute leukemia survivor group had lower rate of smoking (5.6% vs. 25.3%, p 〈 0.001) and drinking in recent 1 year (41.7% vs. 76.7%, p 〈 0.001), and higher rate of influenza vaccination (63.6% vs. 35.4%, p 〈 0.001). Only 17% of the leukemia survivors reported that they had been recommended to receive screening for other cancers from health care providers, and 27% and 40% reported that they thought they had lower risk and similar risk of other cancer than general population. However, this lack of a recommendation for second cancer screening and the misperception of second cancer risk did not have negative impact on cancer screening behaviors (cancer screening in recent 2 years, 45.9% for survivor group vs. 52.3% general population, p = 0.175; health examination, 61.0% vs. 63.2% for, p= 0.632). Conclusion These results indicate that, compared to the general population, survivors of acute leukemia have a significantly worse long-term impact on QoL. Moreover, patients who received SCT for postremission treatment had poorer QoL than those treated with chemotherapy. Health behaviors were comparable between the survivors and the general population. These results can increase the awareness of healthcare providers to the need for counseling and interventions among acute leukemia survivors and help them improve their impaired QOL. Disclosures Yun: Janssen: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 12570-12570
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5683-5683
    Abstract: Although bortezomib-melphalan-prednisone (VMP) therapy is a well-established standard treatment for patients with multiple myeloma (MM) who are ineligible for high-dose therapy, it is not clear whether very elderly patients should be treated with VMP, considering the toxicities. The purpose of this case-control study was to compare the efficacy of VMP versus melphalan-prednisone or cyclophosphamide-prednisone (MP/CP) as initial therapy for very elderly patients. We retrospectively studied 202 patients aged 75 years or older with newly diagnosed multiple myeloma between March 2007 and February 2015. One-hundred twenty two patients received VMP and eighty patients received MP/CP regimen were enrolled from 13 institutions throughout Korea. Patient characteristics were comparable in these two groups. Overall response rate was 69.7% in VMP patients and 47.5% in MP/CP patients (P=0.002). Complete response rate was 24.6% in VMP patients and 10% in MP/CP patients (P=0.005). After a median follow-up for survivors of 28.4 months, progression-free survival was significantly different between the two groups (median 21.0 vs. 11.9 months in VMP and MP/CP group, respectively, P=0.037). Overall survival was also significantly different between the two groups (median 34.6 vs. 27.8 months in VMP and MP/CP group, respectively, P= 0.023). Hematologic grade 3-4 toxicities were more common with VMP (anemia: 29.1% vs 15.3%, P=0.077; thrombocytopenia: 39.3% vs. 15.3%, P 〈 0.001). Grade 2-4 diarrhea (22.5% vs. 2.8%, P = 0.001), vomiting (13.7% vs. 1.4%, P = 0.011), and peripheral sensory neuropathy (35.3% vs. 4.2%, P 〈 0.001) were also more common with VMP. Despite the presence of age-related comorbidities, VMP therapy was associated with modest toxicity, a better response rate and prolonged survival, supporting the use of this effective combination as frontline therapy for very elderly patients with MM. Disclosures Lee: Amgen: Membership on an entity's Board of Directors or advisory committees. Kim:Celltrion, Inc.: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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