RESUMEN
The incidence of severe fever with thrombocytopenia syndrome (SFTS) has increased in Korea since a first report in 2013. We investigated whether SFTS existed before 2013 using real-time reverse transcription polymerase chain reaction and stored blood samples from febrile patients with thrombocytopenia. Four cases of SFTS were identified, with the earliest occurring in 2008.
Asunto(s)
Fiebre/etiología , Linfohistiocitosis Hemofagocítica/diagnóstico , Trombocitopenia/diagnóstico , Médula Ósea/patología , Ferritinas/sangre , Fiebre/diagnóstico , Humanos , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Linfohistiocitosis Hemofagocítica/complicaciones , Masculino , Persona de Mediana Edad , República de Corea , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Trombocitopenia/complicaciones , Adulto JovenRESUMEN
We report a case of acquired thrombotic thrombocytopenic purpura (TTP) triggered by influenza A virus subtype H1N1 infection. In December 2010, a 27-year-old man was diagnosed with pneumonia from influenza A virus infection at a local clinic. Two days later, he was admitted to our hospital because of a worsening condition and unexplained thrombocytopenia. The influenza A virus subtype H1N1 real-time polymerase chain reaction test was positive. The patient had typical clinical signs of TTP, thus he was diagnosed with TTP. He received treatment with oseltamivir and high dose methylprednisolone. Plasma exchange therapy was started daily at a 1.5 dose volume of his whole blood. After the 17th plasma exchange therapy, the symptoms and abnormal laboratory results had recovered to normal. Finally, 47 days after admission, the patient had recovered completely and was discharged. This case suggests that the influenza A virus subtype H1N1 infection may have triggered acquired TTP.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/complicaciones , Neumonía Viral/complicaciones , Púrpura Trombocitopénica Trombótica/etiología , Adulto , Antiinflamatorios/administración & dosificación , Antivirales/administración & dosificación , Humanos , Gripe Humana/tratamiento farmacológico , Masculino , Metilprednisolona/administración & dosificación , Oseltamivir/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/virología , Inducción de RemisiónRESUMEN
Clonorchis sinensis is still a common parasite in South Korea. An enzyme-linked immunosorbent assay (ELISA) was developed to replace the usual intradermal test, and its performance in an area of endemicity was evaluated. From 2004 to 2006, 182 adults were included. The patient group consisted of 51 adults; 43 patients showed fluke eggs by microscopy, and 8 had their disease diagnosed clinically. The negative-control group included 131 adults: 98 at low risk and 33 at high risk of infestation. Both intradermal testing and ELISA were performed for all patients, and the sensitivity and specificity were evaluated. Statistical analysis for specificity looked at two groups: those at high risk and those at low risk. The sensitivity of the C. sinensis ELISA was 80.4%, while that of the intradermal test was 56.9% (P = 0.019). The specificities of the C. sinensis ELISA in the low-risk and high-risk groups were 93.9% and 33.3%, respectively, while those of the intradermal test were 85.7% and 30.3%, respectively (P = 0.0968, P = 0.9979). The C. sinensis ELISA may be more useful than the intradermal test; however, because of its low specificity, it may not be used independently for the diagnosis of C. sinensis infestation or a prevalence survey in a high-risk group.
Asunto(s)
Clonorquiasis/diagnóstico , Clonorchis sinensis/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática/métodos , Animales , Anticuerpos Antihelmínticos/sangre , Enfermedades Endémicas , Humanos , Valor Predictivo de las Pruebas , República de Corea , Factores de Riesgo , Pruebas Cutáneas/métodosRESUMEN
We evaluated high-resolution melting (HRM) curve analysis as a tool for detecting rifampin (RIF) and isoniazid (INH) resistance in Mycobacterium tuberculosis in an accurate, affordable, and rapid manner. Two hundred seventeen M. tuberculosis clinical isolates of known resistance phenotype were used. Twenty-nine known rpoB mutant DNAs, including rare mutations, were also included. Four pairs of primers were designed: rpoB-F/R (for codons 516 to 539 of rpoB), rpoB-516F/R (for codons 508 to 536 of rpoB), katG-F/R (for the codon 315 region of katG), and inhA-F/R (for the nucleotide substitution of C to T at position -15 of inhA). An HRM curve was generated for each isolate after real-time PCR differentiated the mutant from the wild-type strains. DNA sequencing of the target regions was performed to confirm the results of the HRM curve analysis. All but one of the 73 RIF-resistant (RIF-R) strains and all 124 RIF-susceptible (RIF-S) isolates were correctly identified by HRM curve analysis of rpoB. Twenty-seven of 29 known rpoB mutants were detected. In HRM curve analysis of katG and inhA, 90 INH-R strains that harbored katG or inhA mutations, or both, and all INH-S strains were correctly identified. Ten phenotypically INH-R strains not harboring katG or inhA mutations were not detected. The HRM curve analysis will be a useful method for detection of RIF and INH resistance in M. tuberculosis in a rapid, accurate, simple, and cost-effective manner.
Asunto(s)
Antituberculosos/farmacología , ADN Bacteriano/genética , Farmacorresistencia Bacteriana , Isoniazida/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Rifampin/farmacología , Tuberculosis/microbiología , Proteínas Bacterianas/genética , Catalasa/genética , Codón/genética , Cartilla de ADN/genética , ARN Polimerasas Dirigidas por ADN/genética , Humanos , Pruebas de Sensibilidad Microbiana/economía , Pruebas de Sensibilidad Microbiana/métodos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Oxidorreductasas/genética , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y Especificidad , Temperatura de TransiciónRESUMEN
Oligonucleotide chips targeting the bacterial internal transcribed spacer region (ITS) of the 16S-23S rRNA gene, which contains genus- and species-specific regions, were developed and evaluated. Forty-three sequences were designed consisting of 1 universal, 3 Gram stain-specific, 9 genus-specific, and 30 species-specific probes. The specificity of the probes was confirmed using bacterial type strains including 54 of 52 species belonging to 18 genera. The performance of the probes was evaluated using 825 consecutive samples that were positive by blood culture in broth medium. Among the 825 clinical specimens, 708 (85.8%) were identified correctly by the oligonucleotide chip. Most (536 isolates, or 75.7%) were identified as staphylococci, Escherichia coli, or Klebsiella pneumoniae. Thirty-seven isolates (4.5%) did not bind to the corresponding specific probes. Most of these also were staphylococci, E. coli, or K. pneumoniae and accounted for 6.3% of total number of the species. Sixty-two specimens (7.5%) did not bind the genus- or species-specific probes because of lack of corresponding specific probes. Among them, Acinetobacter baumannii was the single most frequent isolate (26/62). The oligonucleotide chip was highly specific and sensitive in detecting the causative agents of bacteremia directly from positive blood cultures.
Asunto(s)
Infecciones Bacterianas/diagnóstico , Técnicas Bacteriológicas/métodos , ADN Bacteriano/genética , ADN Espaciador Ribosómico/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Sepsis/diagnóstico , Infecciones Bacterianas/microbiología , Humanos , Sensibilidad y Especificidad , Sepsis/microbiologíaRESUMEN
Incompatibility of human leukocyte antigen (HLA) alleles between donors and recipients of unrelated hematopoietic stem cell transplantation (UHSCT) increases the risk of acute graft-versus-host disease (GVHD). We evaluated the positional effect of amino acid substitutions in HLA molecules on severe acute GVHD in Korean pediatric recipients of UHSCT. All of 64 donor-recipient pairs were serologically matched for HLA-A, -B, and -DR loci. Only substitution at residue 9 resulting from an HLA-A*02 polymorphism was significantly associated with the risk of severe acute GVHD in patients (OR=7.0, P=0.033) on multivariate analysis. Recipients of this mismatched HLA also showed shortened overall survival (HR=9.7, P<0.001) and increased risk for transplant-related mortality (HR=9.1, P=0.027). Structural modeling showed that the amino acid substitution could alter the peptide preference of the ligand-binding pocket. A single amino acid substitution at position 9 was a major predictor of severe acute GVHD in Korean pediatric patients.
Asunto(s)
Enfermedad Injerto contra Huésped/genética , Antígeno HLA-A2/genética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Pueblo Asiatico/genética , Niño , Preescolar , Femenino , Antígeno HLA-A2/inmunología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Prueba de Histocompatibilidad , Humanos , Lactante , Recién Nacido , Leucemia Mieloide Aguda/terapia , Modelos Logísticos , Masculino , Modelos Moleculares , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , República de CoreaRESUMEN
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an increasingly common worldwide and colonizing S. aureus strains may serve as the causative pathogen for overt clinical infections. This study was performed to determine whether the pathogenic CA-MRSA isolate in clinical infections was genetically related to the MRSA isolates in community carriers. We prospectively collected a total of 42 CA-MRSA isolates (23 clinical infection isolates and 19 colonization isolates) in a local region of Korea. Antimicrobial susceptibility tests, staphylococcal toxin assays, SCCmec typing, multilocus sequence typing (MLST), and spa (staphylococcal protein A) typing were performed with all isolates. Thirty-four (81%) of 42 CA-MRSA isolates belonged to sequence type (ST) 72 in the MLST analysis. The distribution of STs did not differ significantly between colonization and clinical infection isolates (89.5% [17/19] vs. 73.9% [17/23], P=0.26). Among the ST72-MRSA isolates, spa type t664 (18, 52.9%) and t324 (8, 23.5%) were common in both groups. This study demonstrates that the community-associated MRSA strains from patients with clinical infections are closely related to the strains found in carriers from one local community.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina/genética , Infecciones Estafilocócicas/microbiología , Infecciones Comunitarias Adquiridas/microbiología , Genotipo , Humanos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , República de CoreaRESUMEN
The Beijing family of Mycobacterium tuberculosis has been emerging in the world. However, there are few nationwide data of genotypic distribution in Korea. This study aimed to identify the genotypic diversity of clinical isolates of M. tuberculosis and to demonstrate the population of Beijing family in Korea. We collected 96 clinical M. tuberculosis isolates from 11 university hospitals nationwide in Korea from 2008 to 2009. We observed 24 clusters in IS6110-RFLP analysis and 19 patterns in spoligotyping. Seventy-five isolates were confirmed to be Beijing family. Two isolates of the K strain and 12 isolates of the K family strain were also found. We found that drug resistance phenotypes were more strongly associated with Beijing family than non-Beijing family (P=0.003). This study gives an overview of the distribution of genotypes of M. tuberculosis in Korea. These findings indicate that we have to pay more attention to control of M. tuberculosis strains associated with the Beijing family.
Asunto(s)
Mycobacterium tuberculosis/clasificación , Tuberculosis/epidemiología , Farmacorresistencia Bacteriana , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Fenotipo , Polimorfismo de Longitud del Fragmento de Restricción , República de Corea , Tuberculosis/genética , Tuberculosis/microbiologíaRESUMEN
We evaluated a new immunochromatographic assay (ICA) using mouse monoclonal anti-MPT64 antibody for rapid discrimination between Mycobacterium tuberculosis and nontuberculous mycobacteria in clinical isolates. A study with mycobacteria and other organisms showed excellent sensitivity (approximately equal 99%) and specificity (100%) and an appropriate detection limit (10(5) CFU/ml) when tested with M. tuberculosis H37Rv. This ICA can simplify the identification of M. tuberculosis in clinical laboratories.
Asunto(s)
Técnicas Bacteriológicas/métodos , Cromatografía de Afinidad/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis/diagnóstico , Animales , Anticuerpos Monoclonales , Humanos , Inmunoensayo , Ratones , Sensibilidad y Especificidad , Tuberculosis/microbiologíaRESUMEN
BACKGROUND: Chromosomal abnormalities and common genetic rearrangements related to T-acute lymphoblastic leukemia (T-ALL) are not clear. We investigated T-cell receptor (TCR) rearrangement in Korean T-ALL patients by fragment analysis, examining frequency, association between clinicopathologic characteristics and TCR clonality, and feasibility for detecting minimal residual disease (MRD). METHODS: In 51 Korean patients diagnosed as having T-ALL, TCR rearrangement was analyzed using the IdentiClone TCR gene clonality assay (InVivoScribe Technologies, San Diego, CA, USA) from archived bone marrow specimens. Limit of detection (LOD) and clonal stability at relapse were evaluated. The association between clinical prognosis and TCR clonality was examind by age and immunophenotypic classification. RESULTS: Thirty-eight patients (74.5%) had 62 clonal products of TCRß, TCRγ, and/or TCRδ rearrangements at diagnosis. Children with T-ALL (<12 years) showed a higher frequency of clonality (93.8%) than adolescents/adults (65.7%; ≥12 years). Patients with a mature immunophenotype (84.4%) showed a relatively higher frequency of clonality than those with the immature immunophenotype (57.9%). Survival and event-free survival were not influenced by immunophenotype or TCR clonality. The LOD was 1%. Clonal evolution at the relapse period was noted. CONCLUSIONS: The overall detection rate of TCR clonality was 74.5%. Survival did not differ by TCR clonality or immunophenotype and age group. Fragment analysis of TCR rearrangement cannot be used to assess MRD due to low sensitivity. Further research on the relationship between prognosis and frequency of TCR rearrangements is needed, using more sensitive methods to detect clonality and monitor MRD.
Asunto(s)
Reordenamiento Génico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Adolescente , Adulto , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/metabolismo , Niño , Femenino , Humanos , Inmunofenotipificación , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Supervivencia sin Progresión , Recurrencia , Inducción de Remisión , Tasa de Supervivencia , Adulto JovenRESUMEN
ATP-binding cassette transporter G2 (ABCG2) is the most recently described transporter of the multidrug-resistance pump and it promotes resistance to anticancer drugs such as doxorubicin, mitoxantrone, topotecan, and SN-38. Of the ABCG2 polymorphisms, V12M and Q141K alter the functional activity of the ABCG2 transporter and influence the drug response and various toxicities to chemotherapeutic agents. We therefore evaluated the impact of the ABCG2 V12M and Q141K polymorphisms on the therapeutic outcomes and toxicities of primary rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in 145 Korean patients with diffuse large B-cell lymphoma (DLBCL). ABCG2 V12M and Q141K genotyping was carried out by pyrosequencing of polymerase chain reaction products. The clinical characteristics, treatment outcomes, toxicities of the patients, and the predictive value of the polymorphisms on response, survival, and adverse events to R-CHOP for 145 patients were analyzed according to the ABCG2 V12M and Q141K polymorphisms. No differences were observed according to ABCG2 Q141K and V12M genotype in patient characteristics, disease characteristics, response, survival, or hematology toxicity profiles in patients with DLBCL who received frontline R-CHOP chemotherapy. On multivariate analysis, grade I-IV diarrhea was statistically significant according to ABCG2 Q141K polymorphism (the QQ genotype vs the QK or KK genotypes; hazard ratio 2.835; 95% confidence interval 1.432-5.613; P = 0.003). This study demonstrates that the ABCG2 Q141K polymorphism may correlate with chemotherapy-induced diarrhea in patients with DLBCL who have received frontline R-CHOP chemotherapy, and this has implications for optimizing treatment with such agents.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Proteínas de Neoplasias/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino , Ciclofosfamida/administración & dosificación , Diarrea/inducido químicamente , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo Genético , Prednisona/administración & dosificación , Rituximab , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificación , Adulto JovenRESUMEN
A 26-year-old man who had a history of recurrent spontaneous nasal bleeding was admitted to our hospital with uncontrolled traumatic subdural hemorrhage. His plasma factor VII activity was less than 10% of normal. DNA sequence analysis revealed that the proband had a compound heterozygote for a novel nonsense mutation (F7 NM_000131.2 c.345C > A; p.Cys115X) in exon 4 encoding the EGF1 domain and a known missense mutation (F7 NM_000131.2 c.1027G > A; p.Gly343Ser) in exon 8 encoding the serine protease domain of F7. The same F7 Gly343Ser mutation was present in the asymptomatic father, who exhibited a modest reduction in the plasma level of factor VII activity (48%).
Asunto(s)
Deficiencia del Factor VII/genética , Hematoma Subdural/etiología , Mutación Missense/genética , Mutación Puntual/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Análisis Mutacional de ADN , Deficiencia del Factor VII/complicaciones , Heterocigoto , Humanos , Masculino , Relación Estructura-ActividadRESUMEN
We evaluated the UF-100 flow cytometer (TOA Medical Electronics, Kobe, Japan) as a screening test for community-acquired urinary tract infection (UTI) to reduce the need for bacterial cultures. By comparing the test results for 330 urine samples with quantitative urine cultures, we established cutoff criteria for the UF-100. To rule out hospital-acquired UTI, all urine samples were from new patients who had not been admitted to a hospital within the previous month. Abacterial cutoff value of 3,000/microL provided the best discrimination for community-acquired UTI, with a sensitivity of 94.4% and a specificity of 73.4%compared with urine culture. It was possible to forgo 58.2% of cultures with only 4 false-negative results. With a bacterial cutoff value of 1,500/microL, the sensitivity improved to 100%, but the specificity declined to 49.8%, and only 38.5% of cultures could be avoided without any false-negative results. Screening with the UF-100 for community-acquired UTI is acceptable for routine use. It would improve the efficiency of the routine microbiology laboratory, and unnecessary antibiotic prescriptions could be reduced.
Asunto(s)
Infecciones Bacterianas/orina , Técnicas Bacteriológicas/estadística & datos numéricos , Infecciones Comunitarias Adquiridas/orina , Urinálisis/instrumentación , Infecciones Urinarias/orina , Orina/microbiología , Humanos , Recuento de Leucocitos , Leucocitos/citología , Valor Predictivo de las Pruebas , Curva ROC , Urinálisis/métodos , Orina/citologíaRESUMEN
The clinical efficacy of a spoligotyping method for discriminating Mycobacterium tuberculosis strains was evaluated. Among the strains other than Beijing or Beijing like family, 30 different spoligotypes out of 39 strains were produced, which included 4 strains not having IS6110 sequence. The oligonucleotide chip-based spoligotyping technique is useful for early screening and detection of clonal proximity of M. tuberculosis isolates.
Asunto(s)
Dermatoglifia del ADN/métodos , Mycobacterium tuberculosis/clasificación , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Tuberculosis/microbiología , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Intergénico/química , ADN Intergénico/genética , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificaciónRESUMEN
AbstractHuman granulocytic anaplasmosis (HGA) is a tick-borne rickettsial zoonosis with fever, thrombocytopenia, and leukopenia. HGA has been reported in Korea in 2013 but it is uncertain how long it has existed. A retrospective study was conducted on patients who underwent bone marrow examination due to fever and cytopenia, with no clear hematologic or microbiologic causes, from 2003 through 2012. Laboratory diagnosis was made by detecting 16S rRNA genes of Anaplasma phagocytophilum from the stored blood samples. Among the 70 patients, five (7.1%) HGA cases were found, and the earliest case dated back to 2006. Two cases met the diagnostic criteria of hemophagocytic lymphohistiocytosis (HLH) and were fatal. Although HGA has been prevalent in Korea since at least 2006, it is not always diagnosed and has posed a possible lethal health risk to the people in Korea. HGA should be considered as a cause of fever with cytopenia or HLH.
Asunto(s)
Anaplasmosis/epidemiología , Adolescente , Adulto , Anaplasmosis/mortalidad , Niño , Preescolar , Femenino , Fiebre , Humanos , Lactante , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
AIMS: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the SFTS virus; primary manifestations are fever, thrombocytopenia, leukopenia and gastrointestinal symptoms. Before an aetiological diagnosis is made, SFTS patients can undergo bone marrow examination due to cytopenias. Although several studies have reported on bone marrow examination in SFTS patients, most do not provide adequate details. Bone marrow findings in SFTS patients were investigated in this study. METHODS: An observational study was conducted in SFTS patients who were hospitalised between 2013 and 2014 in two university hospitals in South Korea. Patients were included in the study if SFTS was confirmed by real-time PCR for the SFTS virus and a bone marrow examination was conducted. The morphologic findings of the bone marrow samples were reviewed. RESULTS: Three cases met the study inclusion criteria. One patient died of multiple organ failure. Haemophagocytosis was evident in the bone marrow samples of all three patients. Histiocytic hyperplasia and haemophagocytosis were more pronounced in the fatal case. One patient was diagnosed as having haemophagocytic lymphohistiocytosis. CONCLUSIONS: Haemophagocytosis in the bone marrow of SFTS patients may be common. In SFTS endemic areas, SFTS should be one of the differential diagnoses of fever of unknown origin with haemophagocytosis in the bone marrow.
Asunto(s)
Médula Ósea/patología , Infecciones por Bunyaviridae/diagnóstico , Leucopenia/diagnóstico , Linfohistiocitosis Hemofagocítica/diagnóstico , Phlebovirus/aislamiento & purificación , Trombocitopenia/diagnóstico , Anciano , Médula Ósea/virología , Examen de la Médula Ósea , Infecciones por Bunyaviridae/virología , Preescolar , Femenino , Fiebre , Humanos , Leucopenia/virología , Linfohistiocitosis Hemofagocítica/virología , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica , Fagocitosis , Reacción en Cadena en Tiempo Real de la Polimerasa , República de Corea , Trombocitopenia/virologíaRESUMEN
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.
RESUMEN
BACKGROUND: Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose. METHODS: Twenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared. RESULTS: The median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (γ=0.5885, P=0.0012) and after chemotherapy (γ=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis. CONCLUSIONS: The NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation.
Asunto(s)
Leucemia Mieloide Aguda/patología , Proteínas Nucleares/genética , Antineoplásicos/uso terapéutico , Médula Ósea/metabolismo , Médula Ósea/patología , Citarabina/uso terapéutico , Daunorrubicina , Humanos , Cariotipo , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Mutación , Proteínas Nucleares/metabolismo , Nucleofosmina , Reacción en Cadena en Tiempo Real de la Polimerasa , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Análisis de Secuencia de ADN , Tirosina Quinasa 3 Similar a fms/genéticaRESUMEN
The genetic variant rs16754 of Wilms tumor gene 1 (WT1) has recently been described as an independent prognostic factor in AML patients. It is of great interest to test whether WT1 single nucleotide polymorphism can be used as a molecular marker in other types of cancer, to improve risk and treatment stratification. We performed sequencing analysis of exons 7 and 9 of WT1, which are known mutational hotspots, in a total of 73 patients with BCR-ABL1-negative myeloproliferative neoplasm (MPN) and 93 healthy controls. No previously reported WT1 mutations were identified in the present study. In Korean patients with BCR-ABL1-negative MPN, WT1 genetic variant rs16754 had no significant impact on clinical outcomes. We observed a significant difference in the allelic frequencies of WT1 rs16754 in Koreans between BCR-ABL1-negative MPN cases and healthy controls. Individuals carrying variant G alleles of WT1 rs16754 showed a relatively low prevalence of BCR-ABL1-negative MPN, compared with those carrying wild A alleles of WT1 rs16754 (Hazard ratio 0.10-0.65, P<0.05). Therefore, possession of the variant G allele of WT1 rs16754 may reduce the risk of developing BCR-ABL1-negative MPN.
Asunto(s)
Pueblo Asiatico/genética , Trastornos Mieloproliferativos/genética , Proteínas WT1/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Exones , Femenino , Proteínas de Fusión bcr-abl/genética , Frecuencia de los Genes , Genotipo , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos/patología , Polimorfismo de Nucleótido Simple , Pronóstico , Modelos de Riesgos Proporcionales , República de Corea , Riesgo , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
We report three patients with normal karyotype (NK) ALL, who showed genetic aberrations as determined by high-resolution single nucleotide polymorphism array (SNP-A) analysis at both diagnosis and relapse. We evaluated the clinical relevance of the SNP-A assay for the detection of subtle changes in the size of affected genetic lesions at relapse as well as the prognostic value of the assay. In our patients, application of the SNP-A assay enabled sensitive detection of cryptic changes affecting clinically important genes in NK ALL. Therefore, this assay seems to be more advantageous compared to other conventional methods such as FISH assay, HemaVision (DNA Technology, Denmark), and conventional karyotyping for the detection of an "unstable genotype" at relapse, which may be associated with microscopic clonal evolution and poor prognosis. Further comprehensive studies are required to confirm the issues presented by our case patients in this report.