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We conducted a prospective evaluation for the dynamic change of γδT cells in peripheral blood (PB) and N-telopeptide of type I collagen in urine (uNTX) of patients diagnosed with multiple myeloma (MM) who underwent their initial treatment with zoledronic acid (ZOA; Zobonic®, TTY, Taiwan). Between March 2012 and November 2015, a total of 35 patients were enrolled, including 25 newly diagnosed MM (NDMM) patients. The percentage of γδT cells in PB was assessed at 20 days prior to the first ZOA infusion, then at day 8, day 64, and day 85 after the infusion. Simultaneously, uNTX levels were measured as well. Thirty-three patients who had received at least one dose of ZOA were included in subsequent analysis. We identified three dynamic change patterns for γδT cells: fluctuated pattern, continuously increasing pattern, and continuously decreasing pattern. Among NDMM patients, those exhibiting a continuously increasing pattern showed a significantly shorter overall survival compared to those with the other two patterns combined (4.7 months vs. 92.9 months, p = 0.037). For uNTX, which levels significantly decreased following ZOA treatment. In conclusion, our findings reveal three distinct dynamic change patterns for γδT cells after ZOA initiation, with continuously increasing pattern being associated with a poor prognosis. These findings prompt further inquiry into the role of γδT cells in MM patients and support the suppressive nature of γδT cells and their associated tumor microenvironment.
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INTRODUCTION AND OBJECTIVES: Repeated joint bleeding in haemophilia patients may lead to haemophilic arthropathy with marked inflammation and synovitis. This study investigated the potential of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET/CT) as a novel diagnostic method for haemophilic arthropathy. MATERIALS AND METHODS: We recruited 20 adult haemophilia patients who reported history of hemarthroses in the shoulder, elbow, hip, knee, or ankle joints. All joints were assessed by power Doppler ultrasonography and radiography, and graded by hyperaemia score and Pettersson score, respectively. Joint pain was evaluated by visual analogue score (VAS). Range of motion (ROM), Haemophilia Joint Health Score (HJHS) and annual joint bleeding rate (AJBR) were recorded. Finally, all participants had whole-body 18 F-FDG PET/CT, and maximum standardized uptake value (SUVmax) of the joints being studied was measured. RESULTS: Thirteen patients had severe haemophilia, and seven had moderate haemophilia. The mean age was 36 years. PET SUVmax showed significant correlations with VAS, ROM, Pettersson score, hyperaemia score, HJHS score and AJBR in all large joints except hip. Joints with pain, hyperaemia and radiographic changes were found to have higher SUVmax than those without these features. Using Youden's index, the optimal cut-off value for early radiographical arthropathy was found to be between 1.9 and 2.0. CONCLUSION: Our study indicates that 18 F-FDG PET/CT imaging correlated well with various conventional diagnostic techniques. It also demonstrated high sensitivity and specificity for early radiographic arthropathy. 18 F-FDG PET/CT imaging may quantitatively evaluate disease activity of most large joints in a single examination and help detect early haemophilic arthropathy.
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Artritis , Hemofilia A , Hiperemia , Enfermedades Vasculares , Adulto , Humanos , Hemofilia A/complicaciones , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18/farmacología , Hemartrosis/diagnóstico por imagen , Hemartrosis/etiología , Ultrasonografía DopplerRESUMEN
INTRODUCTION: Emicizumab mimicking the cofactor function of activated factor VIII (FVIII) restores haemostasis. METHODS: This nationwide observational study aimed to retrospectively investigate efficacy, safety, and cost in 1 year before and up to 3 years after emicizumab prophylaxis for haemophilia A (HA) patients with FVIII inhibitors. RESULTS AND DISCUSSION: A total of 39 severe HA patients with a median age of 23.0 years were enrolled. The median historical peak FVIII inhibitor titre was 174.2 BU/mL with an interquartile range of 56.5-578.8 BU/mL. The median annualized bleeding rate reduced from 24 to 0 events in the first year after emicizumab prophylaxis (p < .01) and sustained in the second and third years. The median annualized joint bleeding rate reduced to 0 and maintained up to 3 years (p < .01). Twenty-seven patients (69.2%) had target joints before emicizumab prophylaxis and only seven patients (17.9%) of them had target joints after prophylaxis. Medical costs, including cost of haemostatic therapy, frequency of outpatient department visits, emergency room visits and hospital admission, were significantly reduced after emicizumab prophylaxis (p < .01). FVIII inhibitor titre decreased after emicizumab prophylaxis. Overall, three (7.7%) patients experienced 202 grade 1 drug-related adverse events after emicizumab prophylaxis. No serious adverse events were reported during emicizumab prophylaxis period. The adherence to emicizumab prophylaxis was 100% up to 3 years. CONCLUSIONS: HA patients with FVIII inhibitors treated with emicizumab prophylaxis resulted in a significant reduction in treated bleeds and associated costs. No new safety events were observed.
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Anticuerpos Biespecíficos , Hemofilia A , Humanos , Adulto Joven , Adulto , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Taiwán , Estudios Retrospectivos , Anticuerpos Biespecíficos/efectos adversos , Hemorragia/prevención & control , Hemorragia/tratamiento farmacológico , Factor VIII/uso terapéuticoRESUMEN
Atypical hemolytic uremic syndrome (aHUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, is a rare but life-threatening systemic disorder caused by the dysregulation of the complement pathway. Current advances in molecular analysis and pathogenesis have facilitated the establishment of diagnosis and development of effective complement blockade. Based on this recent consensus, we provide suggestions regarding the diagnosis and management of aHUS in Taiwan. The diagnosis of aHUS is made by the presence of TMA with normal ADAMTS13 activity without known secondary causes. Although only 60% of patients with aHUS have mutations in genes involving the compliment and coagulation systems, molecular analysis is suggestive for helping establish diagnosis, clarifying the underlying pathophysiology, guiding the treatment decision-making, predicting the prognosis, and deciding renal transplantation. Complement blockade, anti-C5 monoclonal antibody, is the first-line therapy for patients with aHUS. Plasma therapy should be considered for removing autoantibody in patients with atypical HUS caused by anti-CFH or complement inhibitor is unavailable.
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Síndrome Hemolítico Urémico Atípico , Humanos , Síndrome Hemolítico Urémico Atípico/diagnóstico , Síndrome Hemolítico Urémico Atípico/terapia , Síndrome Hemolítico Urémico Atípico/genética , Taiwán , Consenso , Proteínas del Sistema Complemento , PronósticoRESUMEN
INTRODUCTION: The large interpatient variability in the pharmacokinetic (PK) parameters of recombinant Factor VIII (rFVIII) observed in haemophilia A hinders efficient and cost-beneficial prophylactic regimen initiation. Identification of factors influencing the PK of rFVIII may shed more light on personalised treatment. AIM: This study aimed to develop a population PK model in the Taiwanese haemophilia A and evaluate the current national health insurance (NHI) reimbursement guidelines of Taiwan for haemophilia treatment. METHODS: A population PK analysis was established based on 69 Taiwanese with moderate or severe haemophilia A. A nonlinear mixed-effects modelling (NONMEM® ) was used to estimate PK parameters and their variabilities. A Monte Carlo simulation was performed to evaluate different prophylactic regimens. RESULTS: A two-compartment model with first-order elimination best described the rFVIII data. Weight-based allometric scaling was related to clearance and central volume of distribution. Blood type and baseline von Willebrand factor (VWF) were significant covariates for clearance. For single dose simulations, a time achieving target level (> 1 IU/dL) was associated with increasing rFVIII dose and VWF level. The multiple dose simulations showed that > 96.4% of patients with high VWF level (> 200%) had predicted trough level > 1 IU/dL for all dosing regimens (15-40 IU/kg, two to three times weekly). However, for twice weekly dosing, lower percentage (47.62-62.20%) of patients with blood group O and low VWF level (< 50%) achieved a predicted trough level > 1 IU/dL. CONCLUSION: The population PK of rFVIII was successfully developed. Dose adjustment based on blood type and VWF level should be considered.
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Antígenos de Grupos Sanguíneos , Hemofilia A , Enfermedades de von Willebrand , Factor VIII/farmacocinética , Hemofilia A/tratamiento farmacológico , Humanos , Enfermedades de von Willebrand/tratamiento farmacológico , Factor de von Willebrand/farmacocinéticaRESUMEN
Haemophilia care in Taiwan has come a long way over the past 35 years, from the absence of specialised haemophilia treatment centres before 1984 to the establishment of treatment centers in the majority of medical centers, the listing of haemophilia as a catastrophic illness with full treatment reimbursement by the Taiwan National Health Insurance (NHI), and the implementation of full NHI coverage for prophylaxis therapy. This has led to outcome improvements such as reduced bleed-related morbidity and mortality, fewer viral infections, and enhanced overall multi-modality care. Most people with haemophilia (PWH) are now able to live normal, active lives. Early diagnosis has improved through increased awareness, physician education, and prenatal diagnosis; while comprehensive care, including state of the art rehabilitation and orthopaedic management for haemophilic arthropathy, eradication therapy for chronic hepatitis C, and better treatments for human immunodeficiency virus, allows PWH to enjoy a better quality of life and improved survival. Efforts are now being made to raise prophylaxis rates through full NHI reimbursement and the use of extended half-life recombinant factor products. Overall, Taiwan has made great strides in haemophilia care and we would like to share these experiences for the benefit of all healthcare providers involved in haemophilia care.
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Hemofilia A , Hemofilia A/diagnóstico , Hemofilia A/tratamiento farmacológico , Hemorragia , Humanos , Programas Nacionales de Salud , Calidad de Vida , TaiwánRESUMEN
Hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). We conducted this study to investigate the incidence and risk factors of hepatic VOD for patients receiving HSCT in Taiwan. We retrospectively analyzed the data from a nationwide registry for patients receiving HSCT, which was collected by the Taiwan Society of Blood and Marrow Transplantation. The data collection period was from 2009 to 2014. A total 2345 patients were reviewed and 39 patients among them were diagnosed as having hepatic VOD. The cumulative incidence of hepatic VOD in the whole cohort of 2345 patients was 1.66%. In multivariate analysis, disease diagnosis of myelodysplastic syndrome, chronic HCV infection, condition regimens of bulsulfan intravenously administered, and antithymocyte immunoglobulin were independent factors to predict higher risk of hepatic VOD. The overall mortality rate for patients with hepatic VOD was 79%. Patients with hepatic VOD had significant worse survival outcomes when compared with those without hepatic VOD (P = 0.00063). In conclusion, although the incidence is low, hepatic VOD remains a serious complication after HSCT in Taiwan. The findings of this study could be the basis for developing prophylactic or early treatment strategies for hepatic VOD.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/etiología , Enfermedad Veno-Oclusiva Hepática/mortalidad , Sistema de Registros , Adolescente , Adulto , Aloinjertos , Suero Antilinfocítico/administración & dosificación , Suero Antilinfocítico/efectos adversos , Busulfano/administración & dosificación , Busulfano/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Factores de Riesgo , Tasa de Supervivencia , Taiwán/epidemiologíaRESUMEN
INTRODUCTION: Intra-articular platelet-rich plasma (PRP) injection therapy has been extensively applied in clinical practice to treat musculoskeletal disorders such as osteoarthritis, but the treatment for haemophilic arthropathy is rarely reported. AIMS: This study aimed to compare the efficacy of intra-articular PRP vs hyaluronic acid (HA) injections in treating haemophilic arthropathy of knee joints. PATIENTS: Twenty-two haemophilia patients (mean age, 41.1 ± 1.7 [range, 20-50] years) with painful haemophilic arthropathy of the knee were enrolled for this open-label and observer-blind study. METHODS: Eleven patients were treated with a single intra-articular injection of PRP and the other 11 received five consecutively weekly intra-articular injections of HA. Outcome assessment included pain by visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Chinese Version and synovial change determined by ultrasonography. RESULTS: Platelet-rich plasma and HA intra-articular injection showed statistically significant reduction in VAS, WOMAC total score and hyperaemia score from baseline to 6-month post-treatment. Inter-group comparison showed statistically significant difference in the change in VAS score, WOMAC pain score, physical function score and total score at 6 months, wherein PRP group showed sustained beneficial effect than HA group at 6 months. CONCLUSION: Our study demonstrates that, in comparison with five weekly injections of HA, a single PRP injection resulted in better improvement in pain relief and knee joint function, and greater reduction in synovial hyperaemia for up to 6 months. Our results suggest that PRP may be practical and effective for haemophilic knee arthropathy, and further investigation is warranted.
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Hemofilia A/complicaciones , Ácido Hialurónico/uso terapéutico , Artropatías/complicaciones , Artropatías/tratamiento farmacológico , Articulación de la Rodilla/efectos de los fármacos , Plasma Rico en Plaquetas/metabolismo , Adulto , Femenino , Humanos , Ácido Hialurónico/administración & dosificación , Inyecciones Intraarticulares , Artropatías/diagnóstico por imagen , Artropatías/fisiopatología , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Dolor/complicaciones , Rango del Movimiento Articular , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: In 10%-18% of mild-type hemophilia A (HA) patients, mutations cannot be found by routine DNA analysis. OBJECTIVE: We aimed to identify the genetic defects by mRNA analysis of F8 gene in mild HA patients without mutation in exonic DNA. PATIENTS AND METHODS: From 2006 to 2016, we identified F8 exon mutations in 39 of 49 mild HA patients using routine genetic testing. We then evaluated the 10 remaining patients from six unrelated families without exonic DNA mutation by performing cDNA sequence analysis. RESULTS: Nine of the 10 (90%) patients were confirmed to have F8 gene mutation. Eight patients from four unrelated families were notably found to have presence of an aberrant 675-bp fragment. Sequencing of this fragment showed that there were two separate new alternative splicing exons of 35 bp and 55 bp within intron 18, which formed a 90-bp insertion between exon 18 and exon 19 (E18ins90bpE19) in the mRNA. Based on direct sequencing, this alternative splicing transcript appears to have resulted from deep intronic variant c.5999-277G>A of intron 18. CONCLUSIONS: Our study suggests that deep intronic variant of c.5999-277G>A may be a hot spot mutation for mild hemophilia patients without mutation in exonic DNA.
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Alelos , Factor VIII/genética , Hemofilia A/sangre , Hemofilia A/genética , Intrones , Mutación , Fenotipo , Adolescente , Adulto , Anciano , Empalme Alternativo , Secuencia de Bases , Niño , Cromosomas Humanos X , Exones , Estudios de Asociación Genética , Genotipo , Haplotipos , Hemofilia A/diagnóstico , Humanos , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , ARN Mensajero/genética , Análisis de Secuencia de ADN , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: End-stage hemophilic arthropathy is the result of recurrent joint hemarthrosis. Although total hip arthroplasty (THA) and total knee arthroplasty (TKA) can reduce severe joint pain and improve functional activity, controversy remains regarding outcomes after THA and TKA among patients with hemophilia. This study evaluated the risk of adverse outcomes of hemophilia patients who underwent THA and TKA. METHODS: This retrospective cohort study was conducted using data from the National Health Insurance Research Database. Patients who had hemophilia and underwent THA and TKA between 2000 and 2015 were identified. A total of 121 patients with hemophilia and 194,026 patients without hemophilia were included. Through propensity score matching, patients with hemophilia were matched at a 1:4 ratio to patients without hemophilia. Multivariable regression analysis was used to control for confounding variables and compare the risk of postoperative complications and mortality, differences in length of stay, and cost of care for the hospital. RESULTS: After propensity score matching and multivariate regression analysis, the adjusted hazard ratio of postoperative transfusion for hemophilia patients was 5.262 (95% confidence interval [CI] = 3.044-26.565, P < .001) in THA group and 6.279 (95% CI = 3.246-28.903, P < .001) in TKA group, when compared with the control group. Patients with hemophilia had longer length of hospital stay (THA group: 95% CI, 1.541-2.669, P < .001; TKA group: 95% CI, 1.568-2.786; P < .001) and higher total hospital charges (THA group: 95% CI, 3.518-8.293, P < .001; TKA group: 95% CI, 3.584-8.842; P < .001) compared to patients without hemophilia. Hemophiliacs had a higher yet nonsignificant 1-year infection rate (8.11% vs 3.38%, P = .206) in the THA group. There were no differences between the rates of 30-day and 90-day complications, 1-year infection, reoperation and mortality between the hemophilia and nonhemophilia groups. CONCLUSION: Hemophilia patients have higher rates of postoperative transfusion, hospital costs, and increased length of stay. There is an appreciable clinical difference in 1-year infection rates following THA but our analysis was limited by the small sample size. Other postoperative complications and mortality rates were comparable. Patients with hemophilia should be counseled that infection rate maybe as high as 8% following THA. Further investigation is needed to develop prophylactic and effective methods to decrease the rates of transfusions and associated adverse outcomes in hemophilia patients undergoing THA and TKA.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Hemofilia A/complicaciones , Adolescente , Adulto , Anciano , Transfusión Sanguínea , Bases de Datos Factuales , Femenino , Costos de Hospital , Hospitales , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Puntaje de Propensión , Reoperación/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and acquired hematopoietic stem cell disease, with florid clinical presentations. Although this disease has been characterized in the western countries, its clinical and laboratory features in Taiwan have not yet been reported. RESULTS: As a part of an international prospective, non-interventional, observational registration trial of PNH, we have analyzed 63 patients recruited between 2009 and 2015 in Taiwan, with comparison to the 3857 patients in the rest of the world (ROW). The median age of diagnosis of our patients is 46 (range 9-84), without sex preponderance. While most of the clinical and laboratory presentations of our patients are similar to the ROW, ours have higher lactate dehydrogenase levels, lower hemoglobin, and higher frequencies of symptoms including shortness of breath and erectile dysfunction at the time of diagnosis. The incidence of thromboembolism was not statistically different between ours and the ROW (6.7 % vs 13.5 %, P = 0.178). The patients in Taiwan were treated more frequently with corticosteroid (53.2 % vs 32 %, P < 0.001), but less frequently with cyclosporine/anti-thymocyte globulin and heparin/warfarin, both P < 0.001). CONCLUSIONS: This is the first systematic review on the Taiwanese PNH patients. Our analysis would provide key information about our PNH patients and would help understanding the basic characteristics of this rare disease in Taiwan. TRIAL REGISTRATION: This trial has been registered to ClinicalTrails.gov NCT01374360.
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Multiple myeloma (MM) is characterized by the neoplastic proliferation of monoclonal plasma cells in the bone marrow and results in complications. In Taiwan, melphalan and several novel agents are used to treat myeloma patients who are not candidate for hematopoietic stem cell transplant (HSCT). This retrospective study aimed to evaluate the characteristics, treatment outcome, and prognostic factors of MM patients who were ineligible for HSCT at our institution from October 2000 until November 2012. A total of 101 MM patients were reviewed. The median age was 71.0 years, and median overall survival (OS) was 22.0 months. Most of patients were diagnosed as IgG-type myeloma (55.4 %). The initial presentations included anemia (89.1 %), skeletal events (49.5 %), severe renal insufficiency (30.7 %), and hypercalcemia (28.7 %). With regard to the frontline therapy, thalidomide/steroid was the most common. Infection was the leading cause of death and adverse effects. Treatment with bortezomib, almost in the second- or third-line setting, was associated with longer median OS (35.5 months) and the median time to progression (TTP) (6.0 months). Bortezomib treatment, chemotherapy, International Staging System (ISS) stage I, and better performance status significantly correlated with survival benefit. In the bortezomib-treated subgroup, better treatment response caused excellent median OS (67.7 months) and also significantly delayed TTP. Therefore, this current analysis concluded a median OS of 22 months in myeloma patients ineligible for HSCT at our institution during the past 10 years. The use of bortezomib with better treatment response also achieved significantly better median OS and TTP.
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Antineoplásicos/uso terapéutico , Ácidos Borónicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Pirazinas/uso terapéutico , Anciano , Anciano de 80 o más Años , Bortezomib , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/epidemiología , Estudios Retrospectivos , Taiwán/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND/PURPOSE: There are few studies on heparin-induced thrombocytopenia (HIT) reported from Taiwan and Asian countries. We conducted a prospective study to investigate the frequency of HIT in patients undergoing cardiopulmonary bypass surgeries. METHODS: A cohort of 54 patients was enrolled from January 01, 2010 to October 31, 2011. Patients' clinical information was obtained for 4T score classification. Plasma (2-4 mL) was also collected before surgery and on Days 5 and 10 following heparin administration during the bypass procedure. This was tested for anti-heparin/PF4 antibodies and functional assay using flow cytometry (FC). RESULTS: The mean platelet count for this cohort followed the expected pattern in the postoperative setting. Seven of the 54 (13%) patients had positive antibodies assays before bypass surgery. This increased to 32% on Day 5 and was markedly elevated to 63% on Day 10 after surgery. Only one of the 54 patients (1.8%) was found to have both positive antibody assay and platelet activation, but no clinical HIT/thrombosis developed. CONCLUSION: Our study is the first report on the rates of HIT in the setting of cardiopulmonary bypass surgery in Taiwan and demonstrated no clinical HIT occurrence, despite the high frequency of HIT antibody in our cohort.
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Anticuerpos/sangre , Anticoagulantes/efectos adversos , Puente Cardiopulmonar , Heparina/efectos adversos , Complicaciones Posoperatorias/sangre , Trombocitopenia/inducido químicamente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Periodo Perioperatorio , Recuento de Plaquetas , Estudios Prospectivos , Taiwán , Factores de TiempoRESUMEN
May-Hegglin anomaly (MHA) is a rare autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and inclusion bodies in leukocytes. Recent evidence links MHA to mutations in the MYH9 gene. MHA has not been reported in Taiwan before. We report a 25-year-old Taiwanese man who presented with prolonged bleeding after dental extraction. Examination of peripheral blood smear revealed thrombocytopenia (platelet = 35,000/µL), giant platelets, and Döhle-like cytoplasmic inclusions in neutrophils. A strong family history of thrombocytopenia favored hereditary macrothrombocytopenia over idiopathic thrombocytopenic purpura (ITP). Electron microscopy revealed a spindle shape and parallel order of filaments in the inclusions, consistent with the diagnosis of MHA. We performed mutational analysis using polymerase chain reaction followed by direct sequence of the MYH9 gene for the patient, his maternal uncle and cousin, and all showed the same heterozygous R1933X mutation in exon 40. MHA should be considered when a young patient has thrombocytopenia, frequently misdiagnosed as ITP. Morphological examination of peripheral blood smear, family history tracing and genetic studies are required to make an accurate diagnosis and avoid unnecessary and even harmful therapies such as corticosteroids and splenectomy.
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Diagnóstico Diferencial , Proteínas Motoras Moleculares/genética , Mutación , Cadenas Pesadas de Miosina/genética , Púrpura Trombocitopénica Idiopática/diagnóstico , Trombocitopenia/diagnóstico , Trombocitopenia/genética , Adulto , Humanos , MasculinoRESUMEN
BACKGROUND/PURPOSE: Chronic hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in patients with hemophilia. However, the efficacy and safety of pegylated interferon (PEG-IFN) plus ribavirin (RBV) for hemophilic patients with chronic HCV infection in Taiwan are still unknown. The aim of this study is to report the efficacy and safety of PEG-IFN plus RBV in a single center in Taiwan. METHODS: In an open-label single-treatment one-arm cohort study, 12 hemophilic patients with elevated alanine aminotransferase level more than two times the upper limit of normal for more than 3 months received 180 µg/week of PEG-IFN-α-2a plus RBV 1000-1200 mg/day at a cut-off value of 75 kg. The duration of treatment was 48 weeks for patients with HCV Genotype 1/4 infection and 24 weeks for patients with HCV Genotype 2/3 infection. Efficacy of therapy was expressed as sustained virological response (SVR). RESULTS: Eight patients achieved SVR (66.7%). The SVR rates were 57%, 100%, 100%, and 0% for patients with HCV Genotypes 1, 2, 3, and 4 infection, respectively. Adverse events (AEs) developed in 10 patients (83.3%). Severe thrombocytopenia developed in one patient. However, the patient did not suffer from severe bleeding. CONCLUSION: Our study shows that the SVR rates are similar in hemophilic and nonhemophilic patients with chronic HCV infection who receive PEG-IFN-α-2a plus RBV in Taiwan. The rate of AEs also resembled other studies in nonhemophilic patients in Taiwan. No patient suffered from severe bleeding. However, large-scale, well-conducted studies are still needed to verify the treatment efficacy and safety.
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Antivirales/uso terapéutico , Hemofilia A/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Alanina Transaminasa/sangre , Estudios de Cohortes , Quimioterapia Combinada/métodos , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Taiwán , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
While high-dose therapy and autologous stem cell transplant (ASCT) remain integral to the primary treatment of newly diagnosed transplant-elble multiple myeloma (MM) patients, the challenge of disease progression persists. The primary objective of this meta-analysis is to evaluate the efficacy and safety of tandem ASCT compared to single ASCT. We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing tandem ASCT with single ASCT in patients with newly diagnosed MM. We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials databases for studies published up to January 2024. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and treatment-related mortality (TRM). We used a random-effects model to calculate pooled hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs). Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa Scale. Twelve studies involving 5057 patients met the inclusion criteria. Tandem ASCT was associated with a significantly higher CRR compared to single ASCT (HR 1.33, 95% CI 1.03-1.71, I2 = 15%), but no significant differences were observed in PFS (HR 0.75, 95% CI 0.42-1.34, I2 = 14%), OS (HR 0.60, 95% CI 0.33-1.10, I2 = 27%), or the ORR (RR 0.80, 95% CI 0.59-1.08, I2 = 33%). However, tandem ASCT was associated with a significantly higher risk of TRM (RR 1.78, 95% CI 1.00-3.18, I2 = 0%). Tandem ASCT improves the CRR but does not provide significant benefits in terms of PFS, OS, or ORR compared to single ASCT in patients with newly diagnosed MM. Moreover, tandem ASCT is associated with a higher risk of TRM. The decision to pursue tandem ASCT should be made on an individual basis, carefully weighing the potential benefits and risks in light of each patient's unique clinical situation. Future research should focus on identifying patient subgroups most likely to benefit from tandem ASCT and exploring strategies to optimize the efficacy and safety of this approach in the context of novel agent-based therapies.
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RATIONALE: Anti-CD19-targeted chimeric antigen receptor (CAR) T cell therapy is effective in treating relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This therapy is associated with several side effects that can be life-threatening such as cytokine release syndrome (CRS). However, chylothorax associated with CRS after CAR-T therapy has not been reported. PATIENT CONCERNS: A 23-year-old male diagnosed with DLBCL relapsing after autologous peripheral blood stem cell transplantation was treated with anti-CD19-targeted CAR-T cell therapy. After CAR-T cell transfusion, he developed grade 3 CRS includes fever, dyspnea, tachycardia and hypotension. The symptoms of CRS persisted and chest plain film revealed bilateral pleural effusion. DIAGNOSIS: Chylothorax was confirmed by the pleural effusion analysis that triglyceride level was 1061 mg/dL. Bacterial and fungal culture of pleural fluid reported no pathogen was detected. Cytological examination of pleural effusion revealed no malignant cells. INTERVENTIONS: The chylothorax resolved after treatment with intravenous administration of tocilizumab. OUTCOMES: On 30-day follow-up, the patient was in stable clinical condition with complete remission of DLBCL on whole-body positron emission tomography scan. LESSONS: We reported a rare case of CAR-T associated chylothorax in a patient with relapsed and refractory DLBCL. Grade 3 CRS with high interleukin-6 level was presented in our patient. The symptoms of CRS were improved with tocilizumab treatment and the chylothorax resolved later on. It is suggested that high interleukin-6 releases might induce chyle leakage resulting from activations of endothelium and coagulation. Our finding highlights the occurrence of chylothorax during the course of CAR-T cell therapy and the importance of proper monitoring and prompt management of this life-threatening side effect.
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Quilotórax , Linfoma de Células B Grandes Difuso , Trasplante de Células Madre de Sangre Periférica , Derrame Pleural , Receptores Quiméricos de Antígenos , Masculino , Humanos , Adulto Joven , Adulto , Receptores Quiméricos de Antígenos/uso terapéutico , Receptores de Antígenos de Linfocitos T , Quilotórax/etiología , Quilotórax/terapia , Interleucina-6/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Antígenos CD19 , Derrame Pleural/tratamiento farmacológicoRESUMEN
Haemophilia A patients who develop factor VIII inhibitors pose a challenge with respect to bleeding and orthopaedic management. This is particularly relevant in cases requiring amputation. We present here a case of a patient with severe haemophilia A and inhibitors who had a history of multiple surgeries due to periprosthetic joint infection and a non-healing wound which led to above-knee amputation. Following the implementation of appropriate and suitable transfemoral prosthesis and emicizumab therapy, the patient experienced a significant improvement in mobility and quality of life without any adverse events or bleeding episodes. Additional studies are required to more fully understand treatment options for lower limb amputations in the haemophilia population.
Asunto(s)
Hemofilia A , Ortopedia , Humanos , Hemofilia A/complicaciones , Factor VIII , Calidad de Vida , Amputación QuirúrgicaRESUMEN
BACKGROUND: Recombinant factor VIII-Fc (rFVIIIFc) became available in Taiwan in 2018. Before this date, no people with hemophilia A (PwHA) were enrolled in a clinical trial of rFVIIIFc. We investigated changes in bleeding outcomes and product utilization in PwHA switching from rFVIII to rFVIIIFc. METHODS: Data were collected for Taiwanese PwHA (severe-type) who switched from rFVIII to rFVIIIFc, including annualized bleeding rate (ABR) and weekly dose consumption 12 months pre-switch and > 6 months post-switch. RESULTS: The 51 patients were divided into 3 groups according to their pre-switch treatment: on-demand treatment, intermittent periodic prophylaxis, and regular prophylaxis. In every group, the post-switch median ABR was significantly reduced, with no significant differences between groups. Meanwhile, the post-switch median weekly dose of each group was significantly increased. In 32 patients on pre-switch prophylaxis, switching brought a further reduction in median ABR, associated with a significant increase in median weekly dose. No adverse effects or novel inhibitor development were seen. CONCLUSION: This is the first report from Asia on real-world experience of rFVIIIFc, showing that switching to rFVIIIFc prophylaxis led to further reduction in ABR and increase in weekly dose for all patient groups, even those on pre-switch rFVIII prophylaxis.
Asunto(s)
Hemofilia A , Humanos , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Semivida , Proteínas Recombinantes de Fusión/farmacología , Resultado del Tratamiento , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Hemorragia/prevención & control , Hemorragia/inducido químicamente , Factor VIII/efectos adversosRESUMEN
The half life of recombinant factor VIII-Fc (rFVIII-Fc) for people with hemophilia A (PwHA) varies greatly. Understanding the factors influencing the variation and assessment of rFVIII-Fc half life is important for personalized treatment. Eighty-five severe-type PwHA with rFVIII-Fc treatment receiving an evaluation of half life by the Web-Accessible Population Pharmacokinetic (PK) Service-Hemophilia during 2019-2021 were retrospectively enrolled. The 50-patient PK profiles before 2021 were used for analysis and developing prediction models of half life, and the 35-patient PK profiles in 2021 were used for external validation. The patients in the development cohort were aged 8-64, with a median rFVIII-Fc half life of 20.75 h (range, 8.25-41.5 h). By multivariate linear regression analysis, we found two, four, and five predictors of rFVIII-Fc half life for the blood groups non-O, O patients, and overall patients, respectively, including baseline VWF:Ag, BMI, VWF:activity/VWF:Ag ratio, body weight, O blood group, inhibitor history, HCV infection, and hematocrit. The three prediction equations of rFVIII-Fc half life (T) were respectively developed as T for non-O group patients = -0.81 + 0.63 × (BMI, kg/m2) + 6.07 × (baseline VWF:Ag, IU/mL), T for O group patients = -0.68 + 13.30 × (baseline VWF:Ag, IU/mL) + 0.27 × (BW, kg) - 1.17 × (BMI, kg/m2) + 16.02 × (VWF:activity/VWF:Ag ratio), and T for overall patients = -1.76 + 7.24 × (baseline VWF:Ag, IU/mL) - 3.84 × (Inhibitor history) + 2.99 × (HCV infection) - 2.83 × (O blood group) + 0.30 × (Hct, %), which explained 51.97%, 75.17%, and 66.38% of the half life variability, respectively. For external validation, there was a significant correlation between the predicted and observed half lives in the validation cohort. The median half life deviation was +1.53 h, +1.28 h, and +1.79 h for the equations of non-O group, O group, and overall group patients, respectively. In total, eight predictors influencing rFVIII-Fc half life were identified. Prediction equations of rFVIII-Fc half life were developed for the non-O and O blood groups and overall PwHA with a good degree of external validation. The equations could be applied to patients aged 8-64 without the need for PK blood sampling and clinically valuable for personalized therapy.