Measurable Residual Disease Testing Using Next-Generation Sequencing in Acute Myeloid Leukemia
Seon Young Kim , M.D., Ph.D. and Hee Jin Huh
, M.D., Ph.D.
Editorial2023-07-01
Seon Young Kim , M.D., Ph.D. and Hee Jin Huh
, M.D., Ph.D.
Editorial2023-07-01
Minjeong Nam , M.D., Ph.D. and Eun Young Song
, M.D., Ph.D.
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 Article2023-07-01 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 Article2023-07-01 Clinical Chemistry
Yuhang Deng , M.D., Chao Zhang
, M.D., Jing Wang
, M.M., Jie Zeng
, M.M., Jiangtao Zhang
, M.M., Tianjiao Zhang
, M.D., Haijian Zhao
, M.M., Weiyan Zhou
, M.D., and Chuanbao Zhang
, M.D.
Abstract : Background: Serum C-peptide results from various routine methods used in China are highly variable, warranting well-performing methods to serve as an accuracy base to improve the harmonization of C-peptide measurements in China. We developed an accurate isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC–MS/MS) method for serum C-peptide measurement and explored its use in harmonization. Methods: After protein precipitation with ZnSO4 solution, C-peptide was extracted from serum samples by anion-exchange solid-phase extraction and quantified by ID-LC–MS/MS in positive ion mode. The precision and analytical recovery of the ID-LC–MS/MS method were assessed. Seventy-six serum samples were analyzed using the ID-LC–MS/MS method and six routine immunoassays. Ordinary linear regression (OLR) and Bland-Altman (BA) analyses were conducted to evaluate the relationship between the ID-LC–MS/MS method and routine immunoassays. Five serum pool samples assigned using the ID-LC–MS/MS method were used to recalibrate the routine assays. OLR and BA analyses were re-conducted after recalibration. Results: The within-run, between-run, and total precision for the ID-LC–MS/MS method at four concentrations were 1.0%–2.1%, 0.6%–1.2%, and 1.3%–2.2%, respectively. The analytical recoveries for the ID-LC–MS/MS method at three concentrations were 100.3%–100.7%, 100.4%–101.0%, and 99.6%–100.7%. The developed method and the immunoassays were strongly correlated, with all R2 >0.98. The comparability among the immunoassays was substantially improved after recalibration. Conclusions: The performance of the ID-LC–MS/MS method was carefully validated, and this method can be used to improve the harmonization of serum C-peptide measurements in China.
Original Article2023-07-01 Clinical Microbiology
Jung Wook Kim , Ph.D. and Kwang Jun Lee
, Ph.D.
Abstract : Background: Vancomycin is a treatment option for patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infection. Unfortunately, reduced susceptibility to vancomycin in S. aureus is becoming increasingly common. We developed a method for the rapid and accurate diagnosis of vancomycin-intermediate resistant S. aureus (VISA). Methods: We performed a microbial genome-wide association study to discriminate between VISA and vancomycin-susceptible S. aureus (VSSA) using 42 whole-genome sequences. A TaqMan single-nucleotide polymorphism (SNP) genotyping assay was developed to detect target SNPs in VISA strains. Results: Four SNPs in the VISA strains resulting in nonsynonymous amino-acid substitutions were associated with reduced susceptibility to vancomycin: SA_RS01235 (G203S), SA_RS09725 (V171A), SA_RS12250 (I48F), and SA_RS12550 (G478A). These four SNPs were mainly detected in the typical hospital-associated sequence type (ST)5 clonal lineage. The TaqMan assay successfully detected all four SNPs using as little as 0.2 ng DNA per reaction. Using 10 VSSA and VISA clinical strains each, we validated that the assay accurately discriminates between VISA and VSSA. Conclusions: The TaqMan SNP genotyping assay targeting four SNPs may be an alternative to current standard methods for the rapid detection of vancomycin-intermediate resistance in S. aureus epidemic lineage ST5.
Original Article2023-07-01 Diagnostic Immunology
Haeun Lee , M.D., Hanbi Lee
, M.D., Sang Hun Eum
, M.D., Eun Jeong Ko
, M.D., Ph.D., Ji-Won Min
, M.D., Ph.D., Eun-Jee Oh
, M.D., Ph.D., Chul Woo Yang
, M.D., Ph.D., and Byung Ha Chung
, M.D., Ph.D.
Abstract : Background: The clinical significance of low-level donor-specific anti-HLA antibody (low-DSA) remains controversial. We investigated the impact of low-DSA on posttransplant clinical outcomes in kidney transplant (KT) recipients. Methods: We retrospectively reviewed 1,027 KT recipients, namely, 629 living donor KT (LDKT) recipients and 398 deceased donor KT (DDKT) recipients, in Seoul St. Mary’s Hospital (Seoul, Korea) between 2010 and 2018. Low-DSA was defined as a positive anti-HLA-DSA result in the Luminex single antigen assay (LABScreen single antigen HLA class I - combi and class II - group 1 kits; One Lambda, Canoga Park, CA, USA) but a negative result in a crossmatch test. We compared the incidence of biopsy-proven allograft rejection (BPAR), changes in allograft function, allograft survival, patient survival, and posttransplant infections between subgroups according to pretransplant low-DSA. Results: The incidence of overall BPAR and T cell-mediated rejection did not differ between the subgroups. However, antibody-mediated rejection (ABMR) developed more frequently in patients with low-DSA than in those without low-DSA in the total cohort and the LDKT and DDKT subgroups. In multivariate analysis, low-DSA was identified as a risk factor for ABMR development. Its impact was more pronounced in DDKT (odds ratio [OR]: 9.60, 95% confidence interval [CI]: 1.79–51.56) than in LDKT (OR: 3.76, 95% CI: 0.99–14.26) recipients. There were no significant differences in other outcomes according to pretransplant low-DSA. Conclusions: Pretransplant low-DSA has a significant impact on the development of ABMR, and more so in DDKT recipients than in LDKT recipients, but not on long-term outcomes.
Brief Communication2023-07-01 Clinical Microbiology
Bernard J. Wolff , M.S., Anna Gaines, M.S., Andrew B. Conley
, Ph.D., Emily Norris
, Ph.D., Lavanya Rishishwar
, Ph.D., Aroon T. Chande
, Ph.D., Eungi Yang
, Ph.D., Maureen H. Diaz
, Ph.D., and Jonas M. Winchell
, Ph.D.
Abstract : We developed and assessed the performance of a new multiplex real-time PCR assay for the detection of all Chlamydia species and simultaneous differentiation of Chlamydia psittaci and Chlamydia pneumoniae—two important human respiratory pathogens—in human clinical specimens. Next-generation sequencing was used to identify unique targets to design real-time PCR assays targeting all Chlamydia species, C. psittaci, and C. pneumoniae. To validate the assay, we used a panel of 49 culture isolates comprising seven C. psittaci genotypes, eight C. pneumoniae isolates, seven other Chlamydia species, and 22 near-neighbor bacterial and viral isolates, along with 22 specimens from external quality assessment (EQA) panels and 34 nasopharyngeal and oropharyngeal swabs and cerebrospinal fluid, stool, and sputum specimens previously identified as positive or negative for C. psittaci or C. pneumoniae. The assays were 100% specific, with limits of detection of 7.64– 9.02 fg/μL. The assay results matched with historical assay results for all specimens, except for one owing to the increased sensitivity of the new C. psittaci assay; the results of the EQA specimens were 100% accurate. This assay may improve the timely and accurate clinical diagnosis of Chlamydia infections and provide a greater understanding of the burden of disease caused by these agents.
Brief Communication2023-07-01 Clinical Microbiology
Yun Woo Lee , M.D., So Yun Lim
, M.D., Sol Jin
, M.D., Hye Jin Park
, M.D., Heungsup Sung
, M.D., Ph.D., Mi-Na Kim
, M.D., Ph.D., Seongman Bae
, M.D., Ph.D., Jiwon Jung
, M.D., Ph.D., Min Jae Kim
, M.D., Ph.D., Sung-Han Kim
, M.D., Ph.D., Sang-Oh Lee
, M.D., Ph.D., Sang-Ho Choi
, M.D., Ph.D., Yang Soo Kim
, M.D., Ph.D., and Yong Pil Chong
, M.D., Ph.D.
Abstract : The sensitivity of the (1–3)-β-D-glucan (BDG) diagnostic test for candidemia varies in different clinical settings, and its usefulness in early diagnosis of candidemia is suboptimal. We evaluated the sensitivity of the test for early candidemia prediction. All adult patients with culture-proven candidemia who underwent a serum Goldstream Fungus (1–3)-β-D-Glucan Test within seven days prior to candidemia onset at a tertiary referral hospital between January 2017 and May 2021 were included. Any-positive BDG results within seven days prior to candidemia onset were obtained in 38 out of 93 (40.9%) patients. The positive rate increased when the test was performed near the day of candidemia onset (P=0.04) but reached only 52% on the day of candidemia onset. We observed no significant differences between BDG-positive and -negative groups in terms of underlying disease, risk factors for candidemia, clinical presentation, origin of candidemia, and 30-day mortality. Candida albicans was significantly associated with positive BDG results than with all-negative BDG results (P=0.04). The Goldstream BDG test is unreliable for candidemia prediction because of its low sensitivity. Negative BDG results in patients with a high risk of invasive candidiasis should be interpreted with caution.
Letter to the Editor2023-07-01 Diagnostic Hematology
Heejeong Kim , M.D., In-suk Kim
, M.D., Ph.D., and Hyerim Kim
, M.D., Ph.D.
Letter to the Editor2023-07-01 Clinical Microbiology
Jeong Su Park , M.D., Ph.D., Yun Jung Choi
, B.S., Kyungmi Kwon
, B.S., Seong Jin Choi
, M.D., Ph.D., Song Mi Moon
, M.D., Ph.D., Kyoung-Ho Song
, M.D., Ph.D., Eu Suk Kim
, M.D., Ph.D., Kyoung Un Park
, M.D., Ph.D., and Hong Bin Kim
, M.D., FIDSA
Letter to the Editor2023-07-01 Clinical Microbiology
Kuenyoul Park , M.D., Heungsup Sung
, M.D., Ph.D., and Mi-Na Kim
, M.D., Ph.D
Letter to the Editor2023-07-01 Clinical Microbiology
Yu Been Oh , M.D., Ha Jin Lim
, M.D., Seung A Byun
, M.S., Min Ji Choi
, Ph.D., Hyun-Jung Choi
, M.D., Ph.D., Myung Geun Shin
, M.D., Ph.D., Seung Yeob Lee
, M.D., Ph.D., and Jong Hee Shin
, M.D., Ph.D.
Erratum2023-07-01
Yu Jeong Choi, Young Ah Kim, Kim Junglim, Seok Hoon Jeong, Jong Hee Shin, Kyeong Seob Shin, Jeong Hwan Shin, Young Ree Kim, Hyun Soo Kim, Young Uh, and Nam Hee Ryoo
Ann Lab Med 2023; 43(4): 398-398