Brief Communication2023-09-01 Diagnostic Hematology
Cheonghwa Lee 
, M.D., Ha Nui Kim , M.D., Ph.D., Jung Ah Kwon , M.D., Ph.D., Soo-Young Yoon , M.D., Ph.D., Min Ji Jeon , M.D., Ph.D., Eun Sang Yu , M.D., Dae Sik Kim , M.D., Ph.D., Chul Won Choi , M.D., Ph.D., and Jung Yoon , M.D., Ph.D.
Abstract : The fifth edition of the WHO classification (2022 WHO) and the International Consensus Classification (2022 ICC) of myeloid neoplasms have been recently published. We reviewed the changes in the diagnosis distribution in patients with MDS with excess blasts (MDS-EB) or AML using both classifications. Forty-seven patients previously diagnosed as having AML or MDS-EB with available mutation analysis data, including targeted next-generation and RNA-sequencing data, were included. We reclassified 15 (31.9%) and 27 (57.4%) patients based on the 2022 WHO and 2022 ICC, respectively. One patient was reclassified as having a translocation categorized as a rare recurring translocation in both classifications. Reclassification was mostly due to the addition of mutation-based diagnostic criteria (i.e., AML, myelodysplasia-related) or a new entity associated with TP53 mutation. In both classifications, MDS diagnosis required the confirmation of multi-hit TP53 alterations. Among 14 patients with TP53 mutations, 11 harbored multi-hit TP53 alterations, including four with TP53 mutations and loss of heterozygosity. Adverse prognosis was associated with multi-hit TP53 alterations (P=0.009) in patients with MDS-EB, emphasizing the importance of detecting the mutations at diagnosis. The implementation of these classifications may lead to the identification of different subtypes from previously heterogeneous diagnostic categories based on genetic characteristics.
Original Article2023-07-01 Diagnostic Hematology
Jin Ju Kim , M.D., Ji Eun Jang , M.D., Hyeon Ah Lee , M.S., Mi Ri Park , B.S., Hye Won Kook , M.D., Seung-Tae Lee , M.D., Jong Rak Choi , M.D., Yoo Hong Min , M.D., Saeam Shin , M.D., and June-Won Cheong , M.D.
Abstract : Background: AML is a heterogeneous disease, and despite intensive therapy, recurrence is still high in AML patients who achieve the criterion for cytomorphologic remission (residual tumor burden [measurable residual disease, MRD]0.99). The test reproducibly detected MRD in three dilution series samples, with a sensitivity of 0.25% for single-nucleotide variants. More than half of samples from patients with morphologic remission after one month of chemotherapy had detectable mutations. NGS-MRD positivity for samples collected after one month of chemotherapy tended to be associated with poor overall survival and progression-free survival. Conclusions: Our highly sensitive and accurate NGS-MRD panel can be readily used to monitor most AML patients in clinical practice, including patients without gene rearrangement. In addition, this NGS-MRD panel may allow the detection of newly emerging clones during clinical relapse, leading to more reliable prognoses of AML.
Original Article2023-03-01 Diagnostic Hematology
Inki Moon , M.D., M.S., Min Gyu Kong , M.D., M.S., Young Sok Ji , M.D., M.S., Se Hyung Kim , M.D., Ph.D., Seong Kyu Park , M.D., Ph.D., Jon Suh , M.D., Ph.D., and Mi-Ae Jang , M.D., Ph.D.
Abstract : Background: Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of blood cells originating from somatically mutated hematopoietic stem cells, is common among the elderly and is associated with an increased risk of hematologic malignancies. We investigated the clinical, mutational, and transcriptomic characteristics in elderly Korean individuals with CHIP mutations. Methods: We investigated CHIP in 90 elderly individuals aged ≥60 years with normal complete blood counts at a tertiary-care hospital in Korea between June 2021 and February 2022. Clinical and laboratory data were prospectively obtained. Targeted next-generation sequencing of 49 myeloid malignancy driver genes and massively parallel RNA sequencing were performed to explore the molecular spectrum and transcriptomic characteristics of CHIP mutations. Results: We detected 51 mutations in 10 genes in 37 (41%) of the study individuals. CHIP prevalence increased with age. CHIP mutations were observed with high prevalence in DNMT3A (26 individuals) and TET2 (eight individuals) and were also found in various other genes, including KDM6A, SMC3, TP53, BRAF, PPM1D, SRSF2, STAG1, and ZRSR2. Baseline characteristics, including age, confounding diseases, and blood cell parameters, showed no significant differences. Using mRNA sequencing, we characterized the altered gene expression profile, implicating neutrophil degranulation and innate immune system dysregulation. Conclusions: Somatic CHIP driver mutations are common among the elderly in Korea and are detected in various genes, including DNMT3A and TET2. Our study highlights that chronic dysregulation of innate immune signaling is associated with the pathogenesis of various diseases, including hematologic malignancies.
Original Article2023-09-01 Diagnostic Hematology
Min-Sun Kim , M.D., Chan-Jeoung Park , M.D., Ph.D., Seung Namgoong , B.S., Seung-Il Kim , B.S., Young-Uk Cho , M.D., Ph.D., and Seongsoo Jang , M.D., Ph.D.
Abstract : Background: Delta checks increase patient safety by identifying automated hematology analyzer errors. International standards and guidelines for the complete blood count (CBC) delta check method have not been established. We established an effective, practical CBC delta check method and criteria. Methods: We assessed five delta check methods for nine CBC items (Hb, mean corpuscular volume, platelet count, white blood cell [WBC] count, and five-part WBC differential counts) using 219,804 blood samples from outpatients and inpatients collected over nine months. We adopted the best method and criteria and evaluated them using 42,652 CBC samples collected over two weeks with a new workflow algorithm for identifying test errors and corrections for Hb and platelet count. Results: The median delta check time interval was 1 and 21 days for inpatients and outpatients (range, 1–20 and 1–222 days), respectively. We used delta values at 99.5% as delta check criteria; the criteria varied among the five methods and between outpatients and inpatients. The delta percent change (DPC)/reference range (RR) rate performed best as the delta check for CBC items. Using the new DPC/RR rate method, 1.7% of total test results exceeded the delta check criteria; the retesting and resampling rates were 0.5% and 0.001%, respectively. Conclusions: We developed an effective, practical delta check method, including RRs and delta check time intervals, and delta check criteria for nine CBC items. The criteria differ between outpatients and inpatients. Using the new workflow algorithm, we can identify the causes of criterion exceedance and report correct test results.
Review Article2023-11-01 Diagnostic Hematology
Hideo Wada , M.D., Ph.D., Katsuya Shiraki , M.D., Ph.D., Takeshi Matsumoto , M.D. Ph.D., Hideto Shimpo , M.D., Ph.D., and Motomu Shimaoka , M.D., Ph.D.
Abstract : Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Evidence indicates that not only an abnormal waveform but also peak times and heights in derivative curves of CWA are useful for the evaluation of hemostatic abnormalities. Modified CWA, including the PT with APTT reagent, dilute PT (small amount of tissue factor [TF]-induced clotting factor IX [FIX] activation; sTF/FIXa), and dilute TT, has been proposed to evaluate physiological or pathological hemostasis. We review routine and modified CWA and their clinical applications. In CWA-sTF/FIXa, elevated peak heights indicate hypercoagulability in patients with cancer or thrombosis, whereas prolonged peak times indicate hypocoagulability in several conditions, including clotting factor deficiency and thrombocytopenia. CWA-dilute TT reflects the thrombin burst, whereas clot-fibrinolysis waveform analysis reflects both hemostasis and fibrinolysis. The relevance and usefulness of CWA-APTT and modified CWA should be further investigated in various diseases.
Letter to the Editor2023-03-01 Diagnostic Hematology
Jiyeon Kim , M.D., Miyoung Kim , M.D., Ph.D., Young-Uk Cho , M.D., Ph.D., Sang-Hyun Hwang , M.D., Ph.D., Seongsoo Jang , M.D., Ph.D., Eul-Ju Seo , M.D., Ph.D., Dok Hyun Yoon , M.D., Ph.D., Heounjeong Go , M.D., Ph.D., and Chan-Jeoung Park , M.D., Ph.D.
Original Article2023-07-01 Diagnostic Hematology
Ye-Seul Kim , M.D., Jae-Woong Choi , M.D., Ph.D., Sang Hoon Song , M.D., Ph.D., Ho Young Hwang , M.D., Ph.D., Suk Ho Sohn , M.D., Ji Seong Kim , M.D., Yoonjin Kang , M.D., Ja-Yoon Gu , M.S., Kyung Hwan Kim , M.D., Ph.D., and Hyun Kyung Kim , M.D., Ph.D.
Abstract : Background: Point-of-care testing (POCT) coagulometers are increasingly used for monitoring warfarin therapy. However, in high international normalized ratio (INR) ranges, significant discrepancy in the INR between POCT and conventional laboratory tests occurs. We compared the INR of POCT (CoaguChek XS Plus; Roche Diagnostics, Mannheim, Germany) with that of a conventional laboratory test (ACL TOP 750; Instrumentation Laboratory SpA, Milan, Italy) and explored possible reasons for discrepancy. Methods: Paired POCT and conventional laboratory test INRs were analyzed in 400 samples from 126 patients undergoing warfarin therapy after cardiac surgery. Coagulation factor and thrombin generation tests were compared using the Mann–Whitney U test. Correlations between coagulation factors and INRs were determined using Pearson correlation coefficients. Results: The mean difference in the INR between the tests increased at high INR ranges. Endogenous thrombin potential levels were decreased at INR
Original Article2024-09-01 Diagnostic Hematology
Weiqiang Chen , M. Med., Peiling Yu , M. Med., Chao Chen , M. Med., Shaoyan Cai , M. Med., Junheng Chen , M. Med., Chunqin Zheng , M. Med., Chaojin Chen , M.D., Liangjie Zheng , M.D., and Chunming Guo , M.D.
Abstract : Background: Millions of patients undergo cardiac surgery each year. The red blood cell distribution width (RDW) could help predict the prognosis of patients who undergo percutaneous coronary intervention or coronary artery bypass surgery. We investigated whether the RDW has robust predictive value for the 30-day mortality among patients in an intensive care unit (ICU) after undergoing cardiac surgery. Methods: Using the Medical Information Mart for Intensive Care-IV Database, we retrieved data for 11,634 patients who underwent cardiac surgery in an ICU. We performed multivariate Cox regression analysis to model the association between the RDW and 30-day mortality and plotted Kaplan–Meier curves. Subgroup analyses were stratified using relevant covariates. Receiver operating characteristic (ROC) curves were used to determine the predictive value of the RDWs. Results: The total 30-day mortality rate was 4.2% (485/11,502). The elevated-RDW group had a higher 30-day mortality rate than the normal-RDW group (P
Original Article2024-07-01 Diagnostic Hematology
Yu Jeong Choi , M.D., Ph.D., Young Kyu Min , Ph.D., Seung-Tae Lee , M.D., Ph.D., Jong Rak Choi , M.D., Ph.D., and Saeam Shin , M.D., Ph.D.
Abstract : Background: The three best-known NUP214 rearrangements found in leukemia (SET:: NUP214, NUP214::ABL1, and DEK::NUP214) are associated with treatment resistance and poor prognosis. Mouse experiments have shown that NUP214 rearrangements alone are insufficient for leukemogenesis; therefore, the identification of concurrent mutations is important for accurate assessment and tailored patient management. Here, we characterized the demographic characteristics and concurrent mutations in patients harboring NUP214 rearrangements. Methods: To identify patients with NUP214 rearrangements, RNA-sequencing results of diagnostic bone marrow aspirates were retrospectively studied. Concurrent targeted next-generation sequencing results, patient demographics, karyotypes, and flow cytometry information were also reviewed. Results: In total, 11 patients harboring NUP214 rearrangements were identified, among whom four had SET::NUP214, three had DEK::NUP214, and four had NUP214::ABL1. All DEK::NUP214-positive patients were diagnosed as having AML. In patients carrying SET::NUP214 and NUP214::ABL1, T-lymphoblastic leukemia was the most common diagnosis (50%, 4/8). Concurrent gene mutations were found in all cases. PFH6 mutations were the most common (45.5%, 5/11), followed by WT1 (27.3%, 3/11), NOTCH1 (27.3%, 3/11), FLT3-internal tandem duplication (27.3%, 3/11), NRAS (18.2%, 2/11), and EZH2 (18.2%, 2/11) mutations. Two patients represented the second and third reported cases of NUP214::ABL1-positive AML. Conclusions: We examined the characteristics and concurrent test results, including gene mutations, of 11 leukemia patients with NUP214 rearrangement. We hope that the elucidation of the context in which they occurred will aid future research on tailored monitoring and treatment.
Original Article2024-05-01 Diagnostic Hematology
Mikyoung Park , M.D., Ph.D., Jihyang Lim , M.D., Ph.D., Ari Ahn , M.D., Ph.D., Eun-Jee Oh , M.D., Ph.D., Jaewoo Song , M.D., Ph.D., Kyeong-Hee Kim , M.D., Ph.D., Jin-Yeong Han , M.D., Ph.D., Hyun-Woo Choi , M.D., Ph.D., Joo-Heon Park , M.D., Kyung-Hwa Shin , M.D., Ph.D., Hyerim Kim , M.D., Ph.D., Miyoung Kim , M.D., Ph.D., Sang-Hyun Hwang , M.D., Ph.D., Hyun-Young Kim , M.D., Ph.D., Duck Cho , M.D., Ph.D., and Eun-Suk Kang , M.D., Ph.D.
Abstract : Background: Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCI-HLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization. Methods: Eight university hospitals actively conducting FCI-HLN participated in our survey. We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positive/negative criteria, and reporting. Results: Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positive/negative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included. Conclusions: This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.
Full Text
PDF
Pubmed
PMC
