[Show abstract][Hide abstract] ABSTRACT: For HLA-alloimmunized patients, platelet (PLT) concentrations are provided either at matched HLA-A and HLA-B loci or by serologic cross-reactivity groups (CREG) matching strategy. However, this method has some limitations.
In this study, the epitope-based matching (EBM) method was evaluated for selecting proper HLA-typed PLTs for patients with PLT transfusion refractoriness. Bead-based single-antigen HLA antibody detection method and HLAMatchmaker software were used to define the epitopes recognized by HLA-specific antibodies and to select compatible PLTs for nine patients with alloimmunized refractoriness. Corrected count increments (CCIs) were prospectively determined to compare successful transfusion rates among different matching methods in 142 PLT transfusions. In addition, HLA antibodies were serially detected to see whether any emerging antibodies appeared after receiving the EBM-matched PLTs.
The transfusion success rates evaluated with 1-hour CCIs for perfect matching or lacking any mismatching at HLA-A and -B locus (A/BU)-matched, CREG-matched, and EBM-matched PLTs were 85.2, 63.2, and 83.7%, respectively. Compared to CREG-matched PLTs, EBM-matched PLTs showed better transfusion results (p = 0.035). In the follow-up study (7 months; range, 3-13 months), no emerging HLA-specific antibodies were detected after receiving EBM-matched PLTs.
EBM performed on the basis of bead-based single-antigen HLA antibody detection coupled with the HLAMatchmaker program is recommended in choosing proper PLTs for refractory patients when A/BU-matched PLTs were not available.
[Show abstract][Hide abstract] ABSTRACT: Improved treatment of childhood acute lymphoblastic leukemia (ALL) depends on the identification of new molecular markers that are able to predict treatment response and clinical outcome. The development of impaired apoptosis in leukemic cells is one factor that may influence their response to treatment. We investigated the expression of three apoptosis related genes, BCL2L13, CASP8AP2, and Livin, as well as their prognostic significance, in a retrospective study of 90 pediatric ALL patients diagnosed between 1996 and 2007 in Taiwan. Univariant analysis revealed that high expression of BCL2L13 was associated with inferior event-free survival and overall survival (p<0.001 and 0.005, respectively). Multivariate analysis for EFS and OS demonstrated that high expression of BCL2L13 was an independent prognostic factor for childhood ALL in this ethnic group.
Leukemia research 01/2010; 34(1):18-23. DOI:10.1016/j.leukres.2009.07.023 · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Financial constraints are the main concern in implementing nucleic acid testing (NAT) as routine blood screening in Taiwan. The PROCLEIX ULTRIO assay (Ultrio) on the TIGRIS System (Novartis Diagnostics) was evaluated for its operational performance both for individual-donation testing (IDT) and in minipools of 4 (MP4) to develop a feasible solution.
Analytical sensitivity was determined by testing WHO international standards. We tested 10,290 blood donors, 4210 in IDT and 6080 in MP4. Potential hepatitis B virus (HBV) yield donors (hepatitis B surface antigen [HBsAg] negative/NAT reactive) were evaluated for up to 9 months' follow-up. Discordant results between the Ultrio assay and the HBsAg tests were further analyzed by HBV antibody serology, alternative NATs, HBV DNA quantification, and sequencing.
The 95% limits of detection in IU/mL (95% confidence interval) were as follows: human immunodeficiency virus Type 1 (HIV-1), 18 (12-34); hepatitis C virus (HCV), 4.4 (2.8-8.9); and HBV, 6.3 (4.4-11). The retest rates were 0.55% for IDT and 0.33% for MP4. No HIV or HCV yield cases were found, while there were 12 potential HBV yield cases, nine from IDT and three from MP4 testing. Eleven of them were successfully genotyped as B2. Ten of them returned for follow-up and mostly were determined as occult HBV infection (OBI). The IDT yield rate of 9 in 4210 (0.21%) was fourfold greater than the MP4 yield rate of 3 in 6080 (0.05%; p < 0.05).
The higher yield rate for IDT versus MP4 demonstrates the benefit to implement a more sensitive NAT strategy in regions having significant OBI carriers such as Taiwan.
[Show abstract][Hide abstract] ABSTRACT: This retrospective study evaluates the role of pharmacogenomic determinants in the treatment of childhood acute lymphoblastic leukemia (ALL) in the Taiwanese population.
A total of 105 childhood ALL patients received combined chemotherapy of different intensities based on risk-directed Taiwan Pediatric Oncology Group (TPOG)-ALL-93 protocols. Seventeen genetic polymorphisms in 13 pharmacogenomic targets were analyzed by PCR-based restriction fragment length polymorphism (RFLP) and sequence-specific oligonucleotide (SSO) probe hybridization. Pharmacogenomic polymorphisms were correlated with event-free survival (EFS) of patients, with confounding effects adjusted by multivariate regression.
Three polymorphic alleles in the multi-drug resistance 1 (MDR1) ABCB1 gene, and homozygotic MDR1 2677GG, 3435CC, and 2677G-3435C genotypes were highly associated with a significant reduction in EFS in those patients treated by the standard risk (SR) protocol (TPOG-ALL-93-SR). The hazard ratios were 6.8 (p = 0.01), 21.7 (p = 0.009), and 6.8 (p = 0.01), respectively.
Independent pharmacogenomic determinants associated with treatment outcome were identified in subsets of Taiwanese ALL patients.
[Show abstract][Hide abstract] ABSTRACT: Blood donors in Taiwan currently are screened for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection by immunoassay. The risk of enzyme immunoassay (EIA)-negative, nucleic acid amplification technology (NAT)-reactive donations is not well understood. This study aimed to screen for such donors in Taiwan by a multiplex test (cobas TaqScreen, Roche) on a commercially available NAT system (cobas s 201 system, Roche).
NAT was performed on donors without prescreening in pools of six and NAT-reactive pools were then resolved to the single donation. Individual-donor NAT-reactive samples were discriminated by a commercially available polymerase chain reaction (PCR)-based diagnostic assay (COBAS AmpliScreen, Roche). Samples with EIA- and NAT-discordant results were investigated with supplemental serologic and confirmatory tests. Each sample taken from follow-up of HBV NAT yield cases was tested for HBV serologic profile, NAT, and viral load. The sensitivity and performance efficacy were also evaluated.
The 95 percent limit of detection (LOD) for HBV, HCV, and HIV were 5.09, 11.83, and 62.53 IU per mL, respectively. Among 10,727 seronegative donations, 12 HBV NAT yield cases (0.11%) and 1 HCV NAT yield case (0.01%) were detected. Follow-up results for 1 to 8 months showed that the HCV yield case was a window case and all HBV NAT yield cases were occult carriers.
The use of NAT detected occult HBV and reduced HCV window period. The yield rate, especially occult HBV, was 10- to 100-fold higher than that in developed, HBV nonendemic countries. Therefore, NAT implementation for routine donor screening in a more cost-effective manner should contribute to safer blood transfusion in Taiwan.
[Show abstract][Hide abstract] ABSTRACT: It was estimated that approximately 25 percent of Taiwanese residents were ABO blood group A. Many subgroups of A, however, revealed ambiguous serologic typing results. This study aimed to delineate the molecular basis of the A3, Ax, and weak A phenotypes.
Serologic analyses including adsorption and elution assay, serum transferases activity assay, and saliva test were performed to determine the unique phenotypes of these samples. DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism were performed to further investigate the relationships between the genetic characteristics and phenotypic features of these samples.
Three single-nucleotide transitions (745C>T, 820G>A, and a novel 860C>T) were found in nine A3/A3B cases. In addition, the Ax and A3B subjects shared the same 860C>T mutation. This A(x) allele with 860C>T transition expressed A3B phenotype in A(x)/B101 heterozygote but Ax phenotype in A(x)/O01 heterozygote. This allelic enhancement was also observed in the weak A family with Aw05 allele, which was previously not found in Taiwan.
This allelic enhancement phenomenon was prone to cause serologic discrepancy between parents and children. Genotyping could help us to resolve this problem. Thus, a novel mutation is reported among Taiwanese blood donors.
[Show abstract][Hide abstract] ABSTRACT: Advances in treatment have improved the prognosis in beta-thalassemia major. We present the survival and complications pattern of those patients in northern Taiwan born after 1970.
One-hundred and sixty patients with beta-thalassemia major born after 1970 were collected. The Kaplan-Meier method and log-rank test were used to estimate and compare survival. Cox regression models were used to examine the associations of bone marrow transplantation (BMT), time of BMT procedure, and time of complications with survival.
Better survival was observed for patients born after 1980 (P = 0.0121). Heart disease, BMT-related deaths, and infections were the main causes of death. Among the living patients over age 15, hypogonadotropic hypogonadism, HCV infection, diabetes, heart failure, and arrhythmia were the common complications. No patients under age 15 had complications.
Survival for patients with beta-thalassemia major has improved significantly in Taiwan. More time is required to demonstrate whether these modalities added to the treatment of these patients will impact favorably on their outcome. Our success with BMT is improving and we are now in a position to offer this curative alternative.
[Show abstract][Hide abstract] ABSTRACT: In Taiwan, the prevalence of beta-thalassemia trait is at least 1.1%. The Taiwan government initiated a National Screening Program in 1993. Herein we examine the differences before and after the initiation of this program.
Data consisting of the total number of patients and the birth prevalence beta-thalassemia major were collected. Ninety-one patients with transfusion-dependent thalassemia treated in our hospitals were included for analysis. DNA analysis was performed for 86 patients.
In Taiwan 361 patients exist. The birth prevalence of per 100,000 births was 5.6% in 1994 and declined to 1.21 in 2002. Fourteen patients were born after the program's initiation. DNA analysis of them revealed a new mutation (IVS-1-5 (G-C)), which was introduced through an inter-racial marriage. Otherwise, the remainder was the common beta-thalassemia mutations found in Taiwan.
Despite how successful the National Screening Program is, a few doctors still failed to detect parents at risk. In addition, we are concerned about the emerging problem of the increase of interracial marriages where parents may not have appropriate screening. Hence, postgraduate education programs for physicians, health education for the general population, and timely screening of inter-racial marriage should become a priority.
[Show abstract][Hide abstract] ABSTRACT: Taiwan Pediatric Oncology Group (TPOG)-W-91 is the first multi-institutional Wilms' tumor study for children in Taiwan. This clinical trial used a multidisciplinary approach, based on and similar to the National Wilms' Tumor Study 4. The study was conducted to evaluate the epidemiological characteristics and analyze the outcome of Wilms' tumor patients treated with this protocol.
Ninety eight children with Wilms' tumor (WT) were analyzed for distributions of age, gender, associated congenital anomalies, tumor sites, histology, tumor weights, and clinical stages. Patients received individualized multimodality treatment based upon the histology of the tumor and clinicopathologic stage. The treatment included surgery, radiotherapy and 2-, 3-, and 4-agent active chemotherapeutic agents. Seventy patients were eligible for analysis of treatment outcome. The endpoints were progression-free and overall survival (PFS, OS). Patients were divided into various subgroups according to the chemotherapy regimen used, tumor stage, age at diagnosis, gender, and tumor weight. The prognostic factors were evaluated and the survival rates of various clinical subgroups were compared using log-rank test.
The average annual incidence rate of WT was 2.9 per million children under 15 years of age. The M/F ratio was 1.04. The mean age at diagnosis was 3.7 years. All bilateral tumors occurred in females. Congenital anomalies were present in 17.3% of patients. Anaplastic histology was found in 6 of 98 cases (6.1%). The stage distribution was: I, 43.2%; II, 19.3%; III, 23.9%; IV, 6.8%; and V, 6.8%. The median follow-up time was 89.1 months (range, 1.8 to 128.1 months). The 5-year PFS rate was 0.7841 (SE, 0.0494; 53 of 70 patients) and the 5-year OS rate was 0.886 (SE, 0.038; 63 of 70 patients). Gender was found to be the only significant prognostic variable.
This study evaluated the epidemiological characteristics, clinical features, multimodality therapy regimens, and treatment outcome of WT in Taiwan. Data obtained from this study may lead to further improvement in the prognosis of pediatric malignant solid tumor.
Journal of the Formosan Medical Association 03/2004; 103(2):104-11. · 1.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence and risk factors of hypogonadotropic hypogonadism in transfusion-dependent patients with thalassemia.
The authors examined 29 patients with thalassemia major aged 15 years or older. Luteinizing hormone-releasing hormone tests were performed and beta-thalassemia mutations were analyzed by direct sequencing.
The prevalence of hypogonadotropic hypogonadism was 72%. Failure of puberty was observed in 5 of 11 (45%) boys and 7 of 18 (39%) girls. Arrested puberty was noted in two boys (18%) and five girls (28%). Ten girls (56%) did not menstruate, two (11%) had regular menstrual cycles, one (6%) had irregular menstrual cycles, and five (28%) developed secondary amenorrhea. Twenty-one and eight patients had the beta 0/beta 0 and beta 0/beta+ hematologic phenotypes, respectively. beta 0-thalassemia mutation alleles involved IVS II-654 (C-T), codons 41/42 (-TCTT), codons 27/28 (+C), and codons 17 (A-T). beta+-thalassemia mutations alleles were -28 (A-G) and HbE (codons 26(GAG-AAG)). Hematologic phenotype (odds ratio, 28.50; P = 0.002) was the only risk factor identified in the logistic regression analysis.
In patients with thalassemia major, genetic differences may influence their susceptibility to hypogonadotropic hypogonadism, possibly as a result of differences in the amounts of blood transfused and/or their vulnerability to free radical damage. The hematologic phenotype is a main determinant of the severity of thalassemia major; hence, it may influence the need for and frequency of blood transfusion and the patient's iron-overload status.
[Show abstract][Hide abstract] ABSTRACT: The incidence and clinical spectrum of severe bacterial infection were studied in 89 patients with thalassemia major that was diagnosed between January 1971 and March 2002. There were 20 patients with 24 episodes of severe bacterial infection, resulting in an incidence of 1.6 infections per 100 patient-years. The clinical spectrum included liver abscess (6 cases), septicemia (6 cases), soft-tissue infection (2 cases), osteomyelitis (2 cases), corneal ulcer (1 case), enteritis (1 case), and abscesses of the lung, kidney, intra-abdominal region, retropharynx, gums, and buttocks (1 case each). The leading causal microorganisms were gram-negative bacilli, especially Klebsiella pneumoniae (10 of 20 isolates). Other responsible pathogens were Pseudomonas aeruginosa (2/20), Vibrio vulnificus (2/20), Acinetobacter baumanii (1/20), Streptococcus intermidius (1/20), Yersinia enterocolitica (1/20), Staphylococcus aureus (1/20), Escherichia coli (1/20), and Salmonella species (1/20). Splenectomy and delays in the start of iron-chelating therapy were 2 independent risk factors.
[Show abstract][Hide abstract] ABSTRACT: The superiority of changing postoperative chemotherapy of osteosarcoma based on histological response of the primary tumor over non-tailored chemotherapy has not been confirmed. This multicenter study evaluated the effectiveness of an intensive unstratified chemotherapy regimen in Taiwanese children with osteosarcoma.
Fifty patients younger than 18 years of age with previously untreated non-metastatic osteosarcoma of the extremities were enrolled. Patients were treated with pre- and postoperative chemotherapy, and surgery. Definitive surgery was scheduled in week 7 and postoperative chemotherapy was uniform without stratification regardless of histologic response.
Chemotherapy toxicities were considerable, but manageable. Treatment delay and decreased dose-intensity were common. There was one treatment-related mortality. Forty three patients (86%) received limb salvage surgery and 14 patients (33%) had a good histologic response to preoperative chemotherapy. With a median follow-up of 47.1 months, the 7-year event-free and overall survival rates were 51.6% and 67.6%, respectively.
This was the first multicenter study on the treatment of osteosarcoma from Taiwan. The results suggest that a non-tailored regimen may serve as an alternative treatment strategy in the management of osteosarcoma, particularly when histologic assessment of the tumor response is not available.
Journal of the Formosan Medical Association 07/2003; 102(6):387-93. · 1.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: From 1995-1999, a nation-wide study of Langerhans cell histiocytosis (LCH) in children less than 15 years old was conducted by the Taiwan Pediatric Oncology Group. The demographic and clinical data of 55 cases were analyzed. Thirty-two cases presented from the beginning of 1997 to the end of 1998, when the most severe El Niño in the century occurred. The incidence was higher than expected during this El Niño period (32 cases versus 22 cases, p = 0.003). During 1997-98, most LCH was diagnosed in summer (n = 15), autumn (n = 8), and winter (n = 8) but rarely in spring (n = 1); coincidentally, rainfall was least in winter but peaked in summer. During 1997-98, the most significant increase occurred in the polyostotic LCH subcategory (p = 0.017), with younger ages at diagnosis (p = 0.039). The incidence of LCH cytopenia, fever, and diseases of the skin, liver, spleen or other organs did not differ significantly. Local treatment modality, disseminated diseases and diagnosis during the El Niño of 1997-98 were independent risk factors predicting the recurrence or progression of LCH. Our findings suggest that particular infections or other environmental factors associated with El Niño might be related to the etiology of childhood LCH.
Acta paediatrica Taiwanica = Taiwan er ke yi xue hui za zhi 01/2003; 44(1):14-20.
[Show abstract][Hide abstract] ABSTRACT: Eventhough adjuvant chemotherapy has improved the 5-year survival rate of osteosarcoma patients, a significant percentage of patients eventually die from lung metastasis. Since transforming growth fartor-β (TGF-β) has been demonstrated to be related to the tumor progression, we investigated the clinical implications of the presence of TGF-β isoforms in 16 human osteosarcoma tissue. There were 10 males and 6 females with a mean age of 20.8 years of age (range, 8 to 57 years). Biopsied specimen before chemotherapy was fixed in 10% formalin, demineralized and followed by paraffin embedding. The locations of tumor included femur (10), tibia (3), humerus (1), fibula (1), and ilium (1). Histologic subtypes included osteoblastic (11), chondroblastic (2), and fibroblastic (3). All patients were followed for a minimum of 1 year (range 12 to 44 months) or to the development of lung metastasis. Five patients (31.3%) developed subsequent lung metastasis during the follow up. We used immunohistochemistry technique to investigate the presence of the TGF-β isoforms in osteosarcoma tissue and its relationship to the subsequent pulmonary metastasis. The results showed the presence of one or more TGF-β isoforms in tumor cells in osteosarcoma tissues (13 of 16, 81.3%) in all of the subtypes. However, minimal presence of TGF-β isoforms was shown in the tumor bone matrix. The expression of TGF-β1 or TGF-β3 isoforms was associated with a higher rate of subsequent lung metastasis (p<0.05, chi-square test). Further research is warranted to determine the utility of routine TGF-β analysis in the clinical practice.
The Tohoku Journal of Experimental Medicine 01/1998; 184(2):133-142. DOI:10.1620/tjem.184.133 · 1.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Epstein-Barr virus (EBV), or human herpesvirus-6 (HHV-6) associated haemophagocytic lymphohistiocytosis, has been found prevalent in Taiwan; it affects previously healthy children and is always fatal when treated only supportively. Recognition of the underlying pathogenesis for this disease prompted adoption of an immunomodulatory regimen of intravenous immunoglobulin (IVIG) and/or etoposide on 17 such patients treated between 1990 and 1993. Remarkable improvement in patients’ prognoses was demonstrated. Eight patients are still alive with a median follow-up of 1 year and 2 months post-treatment. Both IVIG and etoposide had positive immunomodulation effects such as alleviation of fever and normalization of haematological and hepatic parameters. Sustained complete response was obtained in two of nine cases of EBV-associated diseases treated with IVIG only. EBV transcripts became undetectable after etoposide and/or IVIG treatment without antiviral agents. Etoposide given by split-dose schedule appeared to be superior to conventional three-consecutive-days schedule for both remission induction and disease-free survival. Our preliminary trial apparently provides a promising improvement in the treatment of this previously fatal disease. IVIG or etoposide is effective in reversing the process of lympho-histiocytic dysregulation resulting from virus infection of immune cells in this syndrome and probably helps hosts to control active virus replication in certain cases, through immunomodulation.
British Journal of Haematology 01/1995; 89(2):282 - 290. DOI:10.1111/j.1365-2141.1995.tb03302.x · 4.71 Impact Factor