ABSTRACT
T-cell large granular lymphocyte (T-LGL) leukemia is characterized by clonal expansion of cytotoxic T cells resulting in cytopenia. The proliferation of clonal LGLs is caused by prolonged antigenic stimulation, which leads to apoptotic dysregulation owing mainly to the constitutive activation of survival pathways, notably the JAK/STAT pathway.Understanding how leukemic T-LGL persists can aid in the development of future immunosuppressive therapies. In this review, we summarize the diagnosis and current standard of therapy for T-LGL leukemia, as well as recent advances in clinical trials.
ABSTRACT
Plasmacytoid dendritic cells (pDCs) are type I interferon-producing cells that modulate immune responses. There are two types of pDC neoplasms: 1) mature pDC proliferation (MPDCP) associated with myeloid neoplasm and 2) blastic pDC neoplasm (BPDCN).MPDCP is a clonal expansion of mature pDCs that is predominantly associated with chronic myelomonocytic leukemia. In contrast, BPDCN is a clinically aggressive myeloid malignancy involving the skin, bone marrow, lymphatic organs, and central nervous system. There are various types of skin lesions, ranging from solitary brown or violaceous to disseminated cutaneous lesions, which often spread throughout the body. The expression of CD4, CD56, CD123, and pDC markers (TCL-1, TCF4, CD303, and CD304, etc.) are typical immunophenotype of BPDCN. Historically, BPDCN treatment has been based on acute leukemia regimens and allogeneic hematopoietic cell transplantation in selected patients. Recent advances in molecular biology and genetics have led to the development of targeted agents, such as tagraxofusp (a recombinant fusion protein targeting CD123), anti-CD123 CAR-T cells, XmAb14045, and IMGN632. Lastly, this review provides a comprehensive overview of pDC neoplasms.
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Background/Aims@#Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. @*Methods@#We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. @*Results@#Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). @*Conclusions@#Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.
ABSTRACT
Genetic hemoglobin disorders are caused by mutations and/or deletions in the α-globin or β-globin genes. Thalassemia is caused by quantitative defects and hemoglobinopathies by structural defect of hemoglobin. The incidence of thalassemia and hemoglobinopathy is increased in Korea with rapid influx of people from endemic areas. Thus, the awareness of the disease is needed. α-thalassemias are caused by deletions in α-globin gene, while β-thalassemias are associated with decreased synthesis of β-globin due to β-globin gene mutations. Hemoglobinopathies involve structural defects in hemoglobin due to altered amino acid sequence in the α- or β-globin chains. When the patient is suspected with thalassemia/hemoglobinopathy from abnormal complete blood count findings and/or family history, the next step is detecting hemoglobin abnormality using electrophoresis methods including high performance liquid chromatography and mass spectrometry. The development of novel molecular genetic technologies, such as massively parallel sequencing, facilitates a more precise molecular diagnosis of thalassemia/hemoglobinopathy. Moreover, prenatal diagnosis using genetic testing enables the prevention of thalassemia birth and pregnancy complications. We aimed to review the spectrum and classification of thalassemia/hemoglobinopathy diseases and the diagnostic strategies including screening tests, molecular genetic tests, and prenatal diagnosis.
Subject(s)
Humans , Amino Acid Sequence , Anemia , Blood Cell Count , Chromatography, Liquid , Classification , Clinical Laboratory Techniques , Diagnosis , Electrophoresis , Erythrocytes , Genetic Testing , Hematology , Hemoglobinopathies , High-Throughput Nucleotide Sequencing , Incidence , Korea , Mass Screening , Mass Spectrometry , Molecular Biology , Parturition , Pregnancy Complications , Prenatal Diagnosis , ThalassemiaABSTRACT
OBJECTIVE: Lumbar discectomy is an effective treatment for lumbar disc herniation (LDH); however, up to 2–18% of patients with LDH have experienced recurrent disc herniation. The purpose of this study was to evaluate the efficacy of a novel annular closure device (ACD) for preventing LDH recurrence and re-operation compared with that of conventional lumbar discectomy (CLD).METHODS: In this prospective randomized controlled trial, we compared CLD with discectomy utilizing the Barricaid® (Intrinsic Therapeutics, Inc., Woburn, MA, USA) ACD. Primary radiologic outcomes included disc height, percentage of preoperative disc height maintained, and re-herniation rates. Additional clinical outcomes included visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, and 12-item short-form health survey (SF-12) quality of life scores. Outcomes were measured at preoperation and at 1 week, 1, 3, 6, 12, and 24 months postoperation.RESULTS: Sixty patients (30 CLD, 30 ACD) were enrolled in this study. At 24-month follow-up, the disc height in the ACD group was significantly greater than that in the CLD group (11.4±1.5 vs. 10.2±1.2 mm, p=0.006). Re-herniation occurred in one patient in the ACD group versus six patients in the CLD group (χ²=4.04, p=0.044). Back and leg VAS scores, ODI scores, and SF-12 scores improved significantly in both groups compared with preoperative scores in the first 7 days following surgery and remained at significantly improved levels at a 24-month follow-up. However, no statistical difference was found between the two groups.CONCLUSION: Lumbar discectomy with the Barricaid® (Intrinsic Therapeutics, Inc.) ACD is more effective at maintaining disc height and preventing re-herniation compared with conventional discectomy. Our results suggest that adoption of ACD in lumbar discectomy can help improve the treatment outcome.
Subject(s)
Humans , Diskectomy , Follow-Up Studies , Health Surveys , Intervertebral Disc Displacement , Leg , Prospective Studies , Quality of Life , Recurrence , Treatment Outcome , Visual Analog ScaleABSTRACT
OBJECTIVE: Lumbar discectomy is an effective treatment for lumbar disc herniation (LDH); however, up to 2–18% of patients with LDH have experienced recurrent disc herniation. The purpose of this study was to evaluate the efficacy of a novel annular closure device (ACD) for preventing LDH recurrence and re-operation compared with that of conventional lumbar discectomy (CLD). METHODS: In this prospective randomized controlled trial, we compared CLD with discectomy utilizing the Barricaid® (Intrinsic Therapeutics, Inc., Woburn, MA, USA) ACD. Primary radiologic outcomes included disc height, percentage of preoperative disc height maintained, and re-herniation rates. Additional clinical outcomes included visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, and 12-item short-form health survey (SF-12) quality of life scores. Outcomes were measured at preoperation and at 1 week, 1, 3, 6, 12, and 24 months postoperation. RESULTS: Sixty patients (30 CLD, 30 ACD) were enrolled in this study. At 24-month follow-up, the disc height in the ACD group was significantly greater than that in the CLD group (11.4±1.5 vs. 10.2±1.2 mm, p=0.006). Re-herniation occurred in one patient in the ACD group versus six patients in the CLD group (χ²=4.04, p=0.044). Back and leg VAS scores, ODI scores, and SF-12 scores improved significantly in both groups compared with preoperative scores in the first 7 days following surgery and remained at significantly improved levels at a 24-month follow-up. However, no statistical difference was found between the two groups. CONCLUSION: Lumbar discectomy with the Barricaid® (Intrinsic Therapeutics, Inc.) ACD is more effective at maintaining disc height and preventing re-herniation compared with conventional discectomy. Our results suggest that adoption of ACD in lumbar discectomy can help improve the treatment outcome.
Subject(s)
Humans , Diskectomy , Follow-Up Studies , Health Surveys , Intervertebral Disc Displacement , Leg , Prospective Studies , Quality of Life , Recurrence , Treatment Outcome , Visual Analog ScaleABSTRACT
No abstract available.
Subject(s)
Bone Marrow , Diagnosis , Korea , Neoplasm Metastasis , Small Cell Lung Carcinoma , Tumor Lysis SyndromeABSTRACT
POEMS syndrome is a rare paraneoplastic syndrome, which includes polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes due to plasma cell (PC) neoplasm. Diagnosis of this disease is challenging because of its rarity and complex clinical manifestations. We attempted to identify the key clinical features and characteristic bone marrow (BM) findings of POEMS syndrome, by reviewing the medical records and BM analyses of 24 Korean patients. Frequent clinical manifestations included polyneuropathy (100%), monoclonal gammopathy (100%), organomegaly (92%), extravascular volume overload (79%), and endocrinopathy (63%). The BM analyses revealed mild PC hyperplasia (median PCs: 5.5%) and frequent megakaryocytic hyperplasia (88%), megakaryocyte clusters (88%), and hyperlobation (100%). Flow cytometry of BM aspirates using CD138/CD38/CD45/CD19/CD56 showed normal (67%, 4/6) or neoplastic PC immunophenotypes (33%, 2/6). A diagnosis of POEMS syndrome must be considered when a patient suspected of having PC dyscrasia shows the above clinical presentation and BM findings.
Subject(s)
Humans , Bone Marrow , Diagnosis , Flow Cytometry , Hyperplasia , Medical Records , Megakaryocytes , Paraneoplastic Syndromes , Paraproteinemias , Plasma Cells , POEMS Syndrome , Polyneuropathies , SkinABSTRACT
No abstract available.
Subject(s)
Bone Marrow , Lymphoma, Follicular , Lymphoma, Mantle-CellABSTRACT
STUDY DESIGN: In-vitro biomechanical investigation. PURPOSE: To evaluate the biomechanical effects of the degeneration of the biodegradable cervical plates developed for anterior cervical discectomy and fusion (ACDF) on fusion and adjacent levels. OVERVIEW OF LITERATURE: Biodegradable implants have been recently introduced for cervical spine surgery. However, their effectiveness and safety remains unclear. METHODS: A linear three-dimensional finite element (FE) model of the lower cervical spine, comprising the C4–C6 vertebrae was developed using computed tomography images of a 46-year-old woman. The model was validated by comparison with previous reports. Four models of ACDF were analyzed and compared: (1) a titanium plate and bone block (Tita), (2) strong biodegradable plate and bone block (PLA-4G) that represents the early state of the biodegradable plate with full strength, (3) weak biodegradable plate and bone block (PLA-1G) that represents the late state of the biodegradable plate with decreased strength, and (4) stand-alone bone block (Bloc). FE analysis was performed to investigate the relative motion and intervertebral disc stress at the surgical (C5–C6 segment) and adjacent (C4–C5 segment) levels. RESULTS: The Tita and PLA-4G models were superior to the other models in terms of higher segment stiffness, smaller relative motion, and lower bone stress at the surgical level. However, the maximal von Mises stress at the intervertebral disc at the adjacent level was significantly higher in the Tita and PLA-4G models than in the other models. The relative motion at the adjacent level was significantly lower in the PLA-1G and Bloc models than in the other models. CONCLUSIONS: The use of biodegradable plates will enhance spinal fusion in the initial stronger period and prevent adjacent segment degeneration in the later, weaker period.
Subject(s)
Female , Humans , Middle Aged , Absorbable Implants , Diskectomy , Finite Element Analysis , Intervertebral Disc , Intervertebral Disc Degeneration , Spinal Fusion , Spine , TitaniumABSTRACT
No abstract available.
Subject(s)
Humans , Drug Therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukocytosis , Lymphoma, B-CellABSTRACT
BACKGROUND: It is widely known that the prognosis of acute myeloid leukemia (AML) depends on chromosomal abnormalities. The majority of AML patients relapse and experience a dismal disease course despite initial remission. METHODS: We reviewed the medical records and laboratory findings of 55 AML patients who had relapsed between 2004 and 2013 and who had been treated at the Division of Hematology of the Pusan National University Hospital. RESULTS: The event-free survival (EFS) was related to prognostic karyotype classification at the time of diagnosis and relapse (unfavorable vs. favorable or intermediate karyotypes at diagnosis, 8.2 vs. 11.9 mo, P=0.003; unfavorable vs. favorable or intermediate karyotypes at relapse, 8.2 vs. 11.9 mo, P=0.009). The overall survival (OS) was significantly correlated with karyotype classification only at diagnosis (unfavorable vs. favorable or intermediate vs. karyotypes at diagnosis, 8.5 vs. 21.8 mo, P=0.001; unfavorable vs. favorable or intermediate karyotypes at relapse, 8.5 vs. 21.2 mo, P=0.136). A change in karyotype between diagnosis and relapse, which is regarded as a factor of resistance against treatment, was not a significant prognostic factor for OS, EFS, and post-relapse survival (PRS). A Cox proportional hazards model showed that the combined use of fludarabine, cytosine arabinoside, and granulocyte colony-stimulating factor (FLAG) as a salvage regimen, was a significant prognostic factor for OS (hazard ratio=0.399, P=0.010) and the PRS (hazard ratio=0.447, P=0.031). CONCLUSION: The karyotype classification at diagnosis predicts survival including PRS in relapsed AML patients as well as in treatment-naïve patients. We suggest that presently, administration of salvage FLAG could be a better treatment option.
Subject(s)
Humans , Chromosome Aberrations , Classification , Clonal Evolution , Cytarabine , Diagnosis , Disease-Free Survival , Granulocyte Colony-Stimulating Factor , Hematology , Karyotype , Leukemia, Myeloid, Acute , Medical Records , Prognosis , Proportional Hazards Models , RecurrenceABSTRACT
OBJECTIVES: In this study, we characterized human dental pulp cells (HDPCs) obtained by different culture methods to establish the most suitable methodology for dental tissue engineering and regenerative endodontic applications. MATERIALS AND METHODS: HDPCs were isolated by the outgrowth method (HDPCs-OG), the enzymatic digestion method (collagenase/dispase/trypsin, HDPCs-ED), or the combination of both methods (HDPCs-Combined). The expression of mesenchymal stem cell markers (CD105, CD90, and CD73) was investigated. In vitro differentiation capacities of HDPCs into adipogenic, osteogenic, and chondrogenic lineages were compared. Differentiation markers were analyzed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. RESULTS: Our data indicated that whole HDPCs-ED, HPDCs-OG, and HDPCs-Combined could be differentiated into adipogenic, chrondrogenic, and osteogenic cell types. However, we found that the methods for isolating and culturing HDPCs influence the differentiation capacities of cells. HDPCs-OG and HDPCs-ED were preferably differentiated into adipogenic and osteogenic cells, respectively. Differentiation markers shown by RT-PCR and western blotting analysis were mostly upregulated in the treated groups compared with the control groups. CONCLUSIONS: Our findings confirmed that cell populations formed by two different culture methods and the combined culture method exhibited different properties. The results of this study could provide an insight into regenerative endodontic treatment using HDPCs.
Subject(s)
Humans , Antigens, Differentiation , Blotting, Western , Dental Pulp , Digestion , In Vitro Techniques , Mesenchymal Stem Cells , Methods , Polymerase Chain Reaction , Stem Cells , Tissue EngineeringABSTRACT
Disseminated intravascular coagulation (DIC) is a major complication in sepsis patients. We compared the performance of five DIC diagnostic criteria, focusing on the prediction of mortality. One hundred patients with severe sepsis or septic shock admitted to intensive care unit (ICU) were enrolled. Routine DIC laboratory tests were performed over the first 4 days after admission. The overall ICU and 28-day mortality in DIC patients diagnosed from five criteria (International Society on Thrombosis and Haemostasis [ISTH], the Japanese Association for Acute Medicine [JAAM], the revised JAAM [R-JAAM], the Japanese Ministry of Health and Welfare [JMHW] and the Korean Society on Thrombosis and Hemostasis [KSTH]) were compared. Both KSTH and JMHW criteria showed superior performance than ISTH, JAAM and R-JAAM criteria in the prediction of overall ICU mortality in DIC patients (odds ratio 3.828 and 5.181, P = 0.018 and 0.006, 95% confidence interval 1.256–11.667 and 1.622–16.554, respectively) when applied at day 1 after admission, and survival analysis demonstrated significant prognostic impact of KSTH and JMHW criteria on the prediction of 28-day mortality (P = 0.007 and 0.049, respectively) when applied at day 1 after admission. In conclusion, both KSTH and JMHW criteria would be more useful than other three criteria in predicting prognosis in DIC patients with severe sepsis or septic shock.
Subject(s)
Humans , Asian People , Dacarbazine , Diagnosis , Disseminated Intravascular Coagulation , Hemostasis , Intensive Care Units , Mortality , Prognosis , Sepsis , Shock, Septic , ThrombosisABSTRACT
No abstract available.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Anemia, Aplastic/diagnosis , Bone Marrow/pathology , Diagnosis, Differential , Half-Life , Immunohistochemistry , Mutation , Myelodysplastic Syndromes/diagnosis , Retrospective Studies , Tumor Suppressor Protein p53/geneticsABSTRACT
BACKGROUND: The immature platelet fraction (IPF) reflects the degree of reticulated platelets. We evaluated performances of IPF as a biomarker for the discrimination of septic patients from non-septic patients and sepsis severity. METHODS: Total 312 patients admitted between March and July 2013 were enrolled and samples were obtained at admission. Lactate (LA), procalcitonin (PCT), C-reactive protein (CRP), immature granulocyte fraction (IG), immature reticulocyte fraction (IRF), and IPF were analyzed as sepsis biomarkers and their performances were compared. RESULTS: The performance of IPF (area under the curve [AUC]=0.868) in the discrimination of septic patients from non-septic patients was comparable to PCT/CRP/LA/IG (AUC=0.923/0.940/0.781/0.812, P=0.233/0.106/0.186/0.353, respectively), and was significantly better than the IRF (AUC=0.658, P=0.007). Sensitivity (89.8%, 95% confidence interval [CI] 84.9-99.8%) and accuracy (83.2%, 95% CI 78.8-90.0%) of IPF were the best among all biomarkers. The performance of IPF in discriminating septic patients from non-septic patients with local infection showed similar results. However, the IPF could not efficiently discriminate sepsis severity (AUC=0.599), similar to other biomarkers (AUC=0.519-0.752). CONCLUSIONS: The IPF possessed high sensitivity/accuracy in discriminating septic patients from non-septic patients, regardless of local infection status. However, the IPF did not efficiently discriminate sepsis severity. The clinical relevance of IPF as a sepsis biomarker is, therefore, limited to sensitive and accurate discrimination of septic patients from non-septic patients, not discrimination of sepsis severity.