Transfusion support in hematopoietic stem cell transplantation

Jekarl Dong Wook,Kim Jae Kwon,Han Jay Ho,Lee Howon,Yoo Jaeeun,Lim Jihyang,Kim Yonggoo 대한혈액학회 2023 Blood Research Vol.58 No.-

Transfusion support for hematopoietic stem cell transplantation (HSCT) is an essential part of supportive care, and compatible blood should be transfused into recipients. As leukocyte antigen (HLA) matching is considered first and as the blood group does not impede HSCT, major, minor, bidirectional, and RhD incompatibilities occur that might hinder transfusion and cause adverse events. Leukocyte reduction in blood products is frequently used, and irradiation should be performed for blood products, except for plasma. To mitigate incompatibility and adverse events, local transfusion guidelines, hospital transfusion committees, and patient management should be considered.

JAK2 V617F mutation in myelodysplastic syndrome, myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable, refractory anemia with ring sideroblasts with thrombocytosis, and acute myeloid leukemia

Jekarl, Dong Wook,Han, Sang Bong,Kim, Myungshin,Lim, Jihyang,Oh, Eun-Jee,Kim, Yonggoo,Kim, Hee-Je,Min, Woo-Sung,Han, Kyungja Korean Society of Hematology; Korean Society of Bl 2010 Blood Research Vol.45 No.1

<P><B>Background</B></P><P>The JAK2 V617F mutation has been noted in the cases of polycythemia vera, essential thrombocythemia, and primary myelofibrosis patients. This mutation occurs less frequently in acute myeloid leukemia (AML) and other hematologic diseases, such as myelodysplastic syndrome (MDS); myelodysplatic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U); and refractory anemia with ring sideroblasts with thrombocytosis (RARS-T).</P><P><B>Methods</B></P><P>Patients diagnosed with hematologic diseases other than MPN who visited Seoul St Mary's Hospital from January 2007 to February 2010 were selected. A total of 43 patients were enrolled in this study: 12 MDS, 9 MDS/MPN-U, 7 RARS-T, and 15 AML patients. The diseases were diagnosed according to the 2008 WHO classification criteria. Data obtained from JAK2 V617F mutation analysis and cytogenetic study as well as complete blood count and clinical data were analyzed.</P><P><B>Results</B></P><P>Of the 43 patients, 6 (13.9%) harbored the JAK2 V617F mutation. The incidence of the JAK2 V617F mutation in each patient group was as follows: 8.3% (1/12), MDS; 22.2% (2/9), MDS/MPN-U; 14.3% (1/7), RARS-T; and 13.3%, (2/15) AML. The platelet count was higher than 450×10<SUP>9</SUP>/L in 3 of the 6 patients (50%) harboring the JAK2 V617F mutation, and it was in the normal range in the remaining 3 patients. Among the 6 patients, 1 MDS and 1 MDS/MPN-U patients had the 46,XX,del(20)(q11.2) karyotype.</P><P><B>Conclusion</B></P><P>The JAK2 V617F mutation is associated with an increased platelet count in MDS, MDS/MPN-U, RARS-T, and AML patients. Cytogenetic abnormalities of del(20)(q11.2) occurred in 1/3 of patients with the JAK2 V617F mutation but further studies are required to confirm this association.</P>

CD56 antigen expression and hemophagocytosis of leukemic cells in acute myeloid leukemia with t(16;21)(p11;q22)

Jekarl, Dong Wook,Kim, Myungshin,Lim, Jihyang,Kim, Yonggoo,Han, Kyungja,Lee, Ah-Won,Kim, Hee-Je,Min, Woo-Sung Springer-Verlag 2010 INTERNATIONAL JOURNAL OF HEMATOLOGY Vol.92 No.2

Evaluating Diagnostic Tests for Helicobacter pylori Infection Without a Reference Standard: Use of Latent Class Analysis

Dong Wook Jekarl,Hyunyu Choi,Ji Yeon Kim,Seungok Lee,Tae-Geun Gweon,이혜경,Yonggoo Kim 대한진단검사의학회 2020 Annals of Laboratory Medicine Vol.40 No.1

Evaluation of diagnostic tests requires reference standards, which are often unavailable. Latent class analysis (LCA) can be used to evaluate diagnostic tests without reference standards, using a combination of observed and estimated results. Conditionally independent diagnostic tests for Helicobacter pylori infection are required. We used LCA to construct a reference standard and evaluate the capability of non-invasive tests (stool antigen test and serum antibody test) to diagnose H. pylori infection compared with the conventional method, where histology is the reference standard. A total of 96 healthy subjects with endoscopy histology results were enrolled from January to July 2016. Sensitivity and specificity were determined for the LCA approach (i.e., using a combination of three tests as the reference standard) and the conventional method. When LCA was used, sensitivity and specificity were 83.8% and 99.4% for histology, 80.0% and 81.9% for the stool antigen test, and 63.6% and 89.3% for the serum antibody test, respectively. When the conventional method was used, sensitivity and specificity were 75.8% and 71.1% for the stool antigen test and 77.7% and 60.7% for the serum antibody test, respectively. LCA can be applied to evaluate diagnostic tests that lack a reference standard.

Diagnosis of Liver Fibrosis With Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein (WFAM2BP) Among Chronic Hepatitis B Patients

Dong Wook Jekarl,최현주,이승옥,권정현,이성원,유혜인,김명신,김용구,성필수,윤승규 대한진단검사의학회 2018 Annals of Laboratory Medicine Vol.38 No.4

Background: Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP) is a protein with altered glycosylation that reacts with lectin, and was recently identified as a useful non-invasive biomarker for the diagnosis of liver fibrosis in patients with hepatitis C virus infection.This study aimed to evaluate the diagnostic efficacy of WFA-M2BP for liver fibrosis in the context of hepatitis B virus (HBV). Methods: We enrolled 151 patients infected with HBV. Liver biopsy and elastography (Fibroscan) were performed during the initial visit. Fibrosis was graded according to the Knodell histologic activity index (F0–3). WFA-M2BP levels were determined with an automated immunoassay analyzer (M2BPGi, HISCL-5000, Sysmex, Japan). The diagnostic efficacy of WFA-M2BP was compared with those of various conventional or composite biomarkers, including enhanced liver fibrosis (ELF) score, Fibroscan, aspartate transaminase (AST)-toplatelet ratio index (APRI), and FIB-4, based on the area under the ROC curve (AUC) value. Results: The majority of patients were at fibrosis stages F1 and F2. The F2 and F3 AUC values for WFA-M2BP were similar to those for FIB-4, APRI, ELF, and Fibroscan, although the latter showed the best diagnostic efficacy. The diagnostic accuracy of all tested biomarkers for F2 and F3 was 60–70%. In multivariate analysis, WFA-M2BP, ELF, and platelet count significantly predicted stage ≥F2, whereas only platelet count significantly predicted F3. Conclusions: WFA-M2BP can support a diagnosis of liver fibrosis with similar diagnostic efficacy to other biomarkers, and predicted liver fibrosis stage ≥2 among patients with chronic hepatitis B.

Prevalence of p16 Methylation and Prognostic Factors in Plasma Cell Myeloma at a Single Institution in Korea

김현정,Dong Wook Jekarl,김명신,김용구,임지향,한경자,민창기 대한진단검사의학회 2013 Annals of Laboratory Medicine Vol.33 No.1

Background: The primary purpose of this study was to investigate the prevalence and characteristics of p16 methylation and determine the prognostic implications of the clinical data, hematologic data, and p16 methylation changes in plasma cell myeloma (PCM). Methods: We reviewed clinical characteristics and results of laboratory tests and investigated the response to combination chemotherapy and survival time. DNA methylation of the p16 gene was tested by methylation-specific PCR. Clinical significance was evaluated. Results: A total of 103 patients were enrolled in this study. The median patient age was 59.0 yr at diagnosis and the male to female ratio was 1.15:1. According to the International Staging System (ISS), patients were diagnosed as stage: I (N=17, 16.5%), II (N=41, 39.8%), III (N=39, 37.9%), or not classified (N=6). Forty-five (43.7%) patients and 36 (35.0%) patients showed abnormal karyotype and complex karyotype, respectively, on the chromosome study. The p16 methylation was observed in 39 (37.9%) of 103 patients, but there was no significant association between p16 methylation status and other clinical or laboratory factors and survival outcome. Male gender, albumin, and complex karyotype were independent prognostic factors for overall survival according to multivariate analysis (P <0.05). Conclusions: The male gender, low serum albumin level, and complex karyotype were independent poor prognostic factors for PCM. p16 methylation was relatively common in PCM,but did not influence the survival outcome.

Indirect Method for Estimation of Reference Intervals of Inflammatory Markers

Kang Taewon,Yoo Jeaeun,Jekarl Dong Wook,Chae Hyojin,Kim Myungshin,Park Yeon-Joon,Oh Eun-Jee,Kim Yonggoo 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.1

Background: The direct method for reference interval (RI) estimating is limited due to the requirement of resources, difficulties in defining a non-diseased population, or ethical problems in obtaining samples. We estimated the RI for inflammatory biomarkers using an indirect method (RII). Methods: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and presepsin (PSEP) data of patients visiting a single hospital were retrieved from April 2009 to April 2021. Right-skewed data were transformed using the Box-Cox transformation method. A mixed population of non-diseased and diseased distributions was assumed, followed by latent profile analysis for the two classes. The intersection point of the distribution curve was estimated as the RI. The influence of measurement size was evaluated as the ratio of abnormal values and adjustment (n×bandwidth) of the distribution curve. Results: The RIs estimated by the proposed RII method (existing method) were as follows: CRP, 0–4.1 (0–4.7) mg/L; ESR, 0–10.2 (0–15) mm/hr and PSEP, 0–411 (0–300) pg/mL. Measurement sizes ≥2,500 showed stable results. An abnormal-to-normal value ratio of 0.5 showed the most accurate result for CRP. Adjustment values ≤5 or >5 were applicable for a measurement size <25,000 or ≥25,000, respectively. Conclusions: The proposed RII method could provide additional information for RI verification or estimation with some limitations.

Clinical Significance of Inflammatory Biomarkers in Acute Pediatric Diarrhea

Park, Yoonseon,Son, Minji,Jekarl, Dong Wook,Choi, Hyun Yoo,Kim, Sang Yong,Lee, Seungok The Korean Society of Pediatric Gastroenterology 2019 Pediatric gastroenterology, hepatology & nutrition Vol.22 No.4

Purpose: The aim of this study was to evaluate the clinical significance of inflammatory biomarkers in acute infectious diarrhea among children. Methods: Clinical parameters including fever, bacterial and viral etiology based on stool culture and multiplex polymerase chain reaction, and nine biomarkers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and leukocytes in blood and calprotectin, lactoferrin, myeloperoxidase, polymorphonuclear elastase, leukocytes, and occult blood in feces were evaluated in children who were hospitalized due to acute diarrhea without underlying disease. Results: A total of 62 patients were included. Among these patients, 33 had fever, 18 showed bacterial infections, and 40 patients were infected with 43 viruses. Of all the biomarkers, CRP was significantly correlated with fever (p<0.001). CRP, ESR, calprotectin, lactoferrin, myeloperoxidase, fecal leukocytes, and occult blood were significantly associated with infection with bacterial pathogens (p<0.001, p=0.04, p=0.03, p=0.003, p=0.02, p=0.03, p=0.002, respectively). The combination of CRP and fecal lactoferrin at their best cut-off values (13.7 mg/L and $22.8{\mu}g/mL$, respectively) yielded a sensitivity of 72.2%, and a specificity of 95.5% for bacterial etiology compared with their individual use. Conclusion: Blood CRP is a useful diagnostic marker for both fever and bacterial etiology in acute pediatric diarrhea. The combination of CRP and fecal lactoferrin yields better diagnostic capability for bacterial etiology than their use alone for acute diarrhea in children without underlying gastrointestinal disease.

Severe hemolytic disease of the newborn due to anti-Di b treated with phototherapy and intravenous immunoglobulin.

Oh, Eun-Jee,Jekarl, Dong Wook,Jang, Hyun-Sik,Park, Hae-Il,Park, Yeon-Joon,Choi, Hyun Ah,Chun, Chung-Sik,Kim, Yonggoo,Kim, Hyung Hoi Institute for Clinical Science] 2008 Annals of clinical and laboratory science Vol.38 No.1

<P>The Di(b) antigen usually occurs with high incidence, except in certain Asian and South American Indian populations. In general, hemolysis caused by anti-Di(b) is not severe and its clinical course is benign. We report a Korean neonate with severe hemolytic disease of the newborn caused by anti-Di(b). The phenotype and genotype of the Diego blood group system of the patient and his mother were Di(a+b+) and Di(a+b-), respectively. The mother's serum and eluate from the neonate's erythrocytes contained anti-Di(b). This case was successfully managed with phototherapy and high dose iv immunoglobulin. Since most commercial antibody detection panels do not contain Di(b-) red cells, it is important to consider anti-Di(b) in cases of hemolytic disease of the newborn caused by an antibody against a high frequency antigen.</P>

Considerations when using next-generation sequencing for genetic diagnosis of long-QT syndrome in the clinical testing laboratory

Chae, Hyojin,Kim, Jiyeon,Lee, Gun Dong,Jang, Woori,Park, Joonhong,Jekarl, Dong Wook,Oh, Yong Seog,Kim, Myungshin,Kim, Yonggoo Elsevier 2017 Clinica chimica acta Vol.464 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Congenital long-QT syndrome (LQTS) is a potentially lethal cardiac electrophysiologic disorder characterized by QT interval prolongation and T-wave abnormalities. At least 13 LQTS-associated genes have been reported, but the high cost and low throughput of conventional Sanger sequencing has hampered the multi-gene-based LQTS diagnosis in clinical laboratories.</P> <P><B>Methods</B></P> <P>We developed an NGS (next-generation sequencing)-based targeted gene panel for 13 LQTS genes using the Ion PGM platform, and a cohort of 36 LQTS patients were studied for characterization of analytical performance specifications.</P> <P><B>Results</B></P> <P>This panel efficiently explored 212 of all 221 coding exons in 13 LQTS-associated genes. And for those genomic regions covered by the design of the NGS panel, the analytical sensitivity and analytical specificity for all potentially pathogenic variants were both 100% and showed 100% concordance with clinically validated Sanger sequencing results in five major LQTS genes (<I>KCNQ1</I>, <I>KCNH2</I>, <I>SCN5A</I>, <I>KCNE1</I>, and <I>KCNE2</I>).</P> <P><B>Conclusion</B></P> <P>This is the first description of an NGS panel targeting a multi-gene panel of 13 LQTS-associated genes. We developed and validated this robust, high-throughput NGS test and informatics pipeline for LQTS diagnosis suitable for the clinical testing laboratory.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We developed an NGS-based targeted gene panel for 13 LQTS genes using the Ion PGM platform. </LI> <LI> The NGS panel showed 100% concordance with Sanger sequencing in the genomic regions covered by the design of the panel. </LI> <LI> This robust and high-throughput NGS panel and informatics pipeline is suitable for LQTS diagnosis in the clinical testing laboratory. </LI> </UL> </P>