Korean Clinical Laboratory Accreditation Program Quality Standards for Laboratory Management: Identifying a Compliance Gap with World Health Organization Quality System Essentials

Background@#The Laboratory Medicine Foundation (LMF) checklists explain the accreditation requirements of the program and reflect quality standards like those of the Clinical Laboratory Standards Institute (CLSI) or quality system essentials (QSE) of the World Health Organization (WHO). In this study, we have analyzed how the LMF checklists correlate with the 12 QSE elements of the WHO. @*Methods@#The LMF checklists for laboratory management (LM) (version 2019) were classified into the 12 specific QSE elements by five laboratory physicians. Each checklist item was classified into specific element if four or more participants agreed, and into overlapping elements when two or more of them agreed for two different items. Any changes in checklist items and chapter structuring of the checklist since 2009 were investigated. @*Results@#The LM checklists consisted of 183 checklist items, including 20 (10.9%) classified into overlapping QSE elements. The QSE element with the highest number of items was the facilities and safety (62, 33.9%), followed by the personnel (22, 12.0%), and the process control (17, 9.3%). In contrast, QSE elements with the lowest number of items were the customer service (4, 2.2%) and process improvement (4, 2.2%). Items belonging to the customer service and the organization elements have increased since 2017. @*Conclusions@#The LMF checklists reflect current quality goals for clinical laboratories and play a leading role in the laboratory's quality improvement. The results of our study will be of help in potentiating the quality leader role of LMF checklists, and international harmonization of our laboratory accreditation program.

First Case of Plasma Cell Myeloma With Brown Tumor Features Unrelated to Hyperparathyroidism

No abstract available.

Pseudo-Chediak-Higashi granules in myeloid cells in therapy-related AML with RUNX1-RUNX1T1

No abstract available.

The 2016 WHO versus 2008 WHO Criteria for the Diagnosis of Chronic Myelomonocytic Leukemia

The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×10⁹/L and ≥10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification. Application of the 2016 WHO criteria resulted in the exclusion of three (8%) patients who did not fulfill the relative monocytosis criterion and eight (21%) patients with an MPN-associated mutation. These 11 patients formed the 2016 WHO others group; the remaining 27 formed the 2016 WHO CMML group. The significant difference in the platelet count and monocyte percentage between the two groups indicated that the 2016 WHO criteria lead to a more homogenous and improved definition of CMML compared with the 2008 WHO criteria, which may have led to over-diagnosis of CMML. More widespread use of molecular tests and more sophisticated clinical and morphological evaluations are necessary to diagnose CMML accurately.

Cellular Hemoglobin Is a Useful Alternative Parameter when Lipemia Interferes with Hemoglobin Measurement

BACKGROUND: Saline replacement is a difficult and time-consuming procedure employed to measure hemoglobin (Hb) levels when lipaemia interferes with the accurate determination of Hb content. As an alternative method, we tested the reliability of cellular Hb (cHb) measurement. METHODS: Forty-eight lipemic blood samples were analysed with the LH780 (or DxH 800; Beckman Coulter Inc., USA) and ADVIA 2120i (Siemens Healthcare Diagnostics, USA) instruments. We compared the Hb measurements obtained following saline replacement (srHb) with the cHb measurement and with the value of one-third of the hematocrit (1/3Hct). RESULTS: The bias estimate outcomes of cHb with srHb were found to be acceptable at all medical decision points. The average difference between the value of 1/3Hct and initial Hb, srHb, and cHb were 19.7%±3.3%, 2.3%±1.6%, and -0.1%±1.1%, respectively. CONCLUSIONS: cHb measurements may be a feasible alternative to srHb, when lipemia interferes with accurate Hb determinations.

A Case of Therapy-Related Acute Leukemia With Mixed Phenotype With BCR-ABL1 After Treatment of Diffuse Large B-Cell Lymphoma

No abstract available.

Comparison of an international scale method and a log reduction method for monitoring of early molecular response in chronic myeloid leukemia patients

No abstract available.

Minor BCR-ABL1-Positive Acute Myeloid Leukemia Associated With the NPM1 Mutation and FLT3 Internal Tandem Duplication

No abstract available.

Nodal tumor response according to the count of peripheral blood lymphocyte subpopulations during preoperative chemoradiotherapy in locally advanced rectal cancer

PURPOSE: The objective of this prospective study was to evaluate the relationship between the circulating lymphocyte subpopulation counts during preoperative chemoradiotherapy (CRT) and tumor response in locally advanced rectal cancer. MATERIALS AND METHODS: From August 2015 to June 2016, 10 patients treated with preoperative CRT followed by surgery were enrolled. Patients received conventional fractionated radiotherapy (50.4 Gy) with fluorouracil-based chemotherapy. Surgical resection was performed at 4 to 8 weeks after the completion of preoperative CRT. The absolute blood lymphocyte subpopulation was obtained prior to and after 4 weeks of CRT. We analyzed the association between a tumor response and change in the lymphocyte subpopulation during CRT. RESULTS: Among 10 patients, 2 (20%) had evidence of pathologic complete response. In 8 patients with clinically node positive, 4 (50%) had nodal tumor response. All lymphocyte subpopulation counts at 4 weeks after CRT were significantly lower than those observed during pretreatment (p < 0.01). A high decrease in natural killer (NK) cell, count during CRT (baseline cell count − cell count at 4 weeks) was associated with node down staging (p = 0.034). CONCLUSION: Our results suggest that the change of lymphocyte subset to preoperative CRT may be a predictive factor for tumor response in rectal cancer.

Optimum Conditions for the Preparation of Red Blood Cell Suspensions for ABO Antibody Titration

BACKGROUND: There is significant inter-laboratory variation in the ABO antibody (Ab) titer levels of blood samples because a standardized method has not yet been developed. The aim of this study was to identify the best conditions for the preparation of the red blood cell (RBC) suspensions so as to aid the development of a standard ABO Ab titration method. METHODS: Serum samples from apparently healthy adults and RBCs from three different sources (residual EDTA blood from healthy adults, donor blood in citrate-phosphate-dextrose-adenine-1 [CPDA-1], and a commercially available RBC reagent) were used for Ab titrations. We measured the titers for each blood group under various conditions, including the time period of storage (days), the ratio of serum to RBC volume, and the RBC sources. The techniques for room temperature incubation and the indirect antiglobulin test were used for the tube and the gel card test. RESULTS: A storage period of 6 to 7 days significantly affected the Ab titers. Samples with 3% RBCs in a 1:1 serum to RBC volume ratio had significantly lower Ab titers than those with 2% RBCs in a 1:1 ratio or those with 3% RBCs in a 2:1 ratio. There were no significant differences in the Ab titers of RBCs from different sources. CONCLUSIONS: To reduce inter-laboratory variations in ABO Ab titrations, using RBC suspension within five days of storage and applying ratio of serum to RBC volume to 2:1 with 3% RBC in the tube test will be helpful when using home-made RBC suspension.

A Rare Case of Chronic Myelogenous Leukemia and Plasma Cell Myeloma in the Same Patient

No abstract available.

Application of Middleware to Automated Hematology Analyzers / 임상검사와정도관리

BACKGROUND: Test results in a laboratory are simply relayed to the laboratory information system through the interface. Middleware facilitates and manages the interaction between applications across heterogeneous computing platforms. We applied middleware to automated hematology analyzers in a clinical laboratory. METHODS: We used HemLink (Beckman Coulter Korea, Korea) as middleware between the laboratory information system and hematology analyzers. It provides quality control programs including the Westgard multirule chart and moving averages. RESULTS: Unlike the previous system, middleware does not require manual input of the quality control results. Amendment of quality control, if necessary, could be done without the help of hospital information teams. Identification of abnormal results with patient information could be achieved with moving averages. Morphology flags and system flags are checked at remote computers. CONCLUSIONS: Management of quality control results of hematology analyzers was easy via middleware. Thus, middleware could be useful to connect proficiency testing programs with HemLink and to compare results from laboratories using the same middleware.

Current routine practice and clinico-pathological characteristics associated with acute promyelocytic leukemia in Korea

BACKGROUND: Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL. METHODS: We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20-80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012. RESULTS: The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)x10(9)/L and 2.7 to 124.0 (median 54.5)x10(9)/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3-44.1) s and 29 (24-62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of >20 microg/mL. The D-dimer median value was 5,000 (686-55,630) ng/mL. The t(15;17)(q22;q12 and PML-RARA fusion was found in all patients by chromosome analysis and/or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), with turnaround times of 8 (2-19) d and 7 (2-13) d, respectively. All patients received induction chemotherapy: all-trans retinoic acid (ATRA) alone (N=11, 26%), ATRA+idarubicin (N=25, 58%), ATRA+cytarabine (N=3, 7%), ATRA+idarubicin+cytarabine (N=4, 9%). CONCLUSION: Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of PML-RARA is required.

Current routine practice and clinico-pathological characteristics associated with acute promyelocytic leukemia in Korea

BACKGROUND: Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL. METHODS: We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20-80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012. RESULTS: The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)x10(9)/L and 2.7 to 124.0 (median 54.5)x10(9)/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3-44.1) s and 29 (24-62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of >20 microg/mL. The D-dimer median value was 5,000 (686-55,630) ng/mL. The t(15;17)(q22;q12 and PML-RARA fusion was found in all patients by chromosome analysis and/or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), with turnaround times of 8 (2-19) d and 7 (2-13) d, respectively. All patients received induction chemotherapy: all-trans retinoic acid (ATRA) alone (N=11, 26%), ATRA+idarubicin (N=25, 58%), ATRA+cytarabine (N=3, 7%), ATRA+idarubicin+cytarabine (N=4, 9%). CONCLUSION: Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of PML-RARA is required.

Methods for Flow Cytometric Analysis of T Cell Subsets in HIV-infected Patients: 2-Color versus 4-Color

BACKGROUND: Blood CD4+ T-lymphocyte (T4) count is a major clinical marker for the diagnosis and management of AIDS, and flow cytometry is considered the gold standard for T4 enumeration. Our aim was to compare the 2-color and 4-color flow cytometric methods for T-cell subset analysis in HIV-infected patients. METHODS: T-cell subsets such as T3, T4, T8, and CD3+CD4-CD8- double negative T cells (DN T) were analyzed from the whole blood of 40 HIV-infected patients by using both 2-color and 4-color methods on a Cytomics FC500 analyzer. Statistical analyses using simple linear regression, paired t-tests, and Bland-Altman plots were performed. RESULTS: The measured T3 (%), T4 (%), T4 (/microL), T8 (%), T8 (/microL), and DN T (%) differed significantly between the 2 methods (P<0.05), whereas the T4/T8 ratio did not. T3 (%), T4 (%), T4 (/microL), T8 (%), T8 (/microL), and T4/T8 measured by the 2 methods showed good correlation, with correlation coefficients above 0.96, whereas DN T (%) did not. The mean differences in T4 (%) and T8 (%) were 0.39% (limit of agreement (LoA), -1.64~2.43) and 1.26% (LoA, -3.37~5.89), respectively. CONCLUSIONS: Although there were statistically significant differences in the T cell subsets measured between the 2 methods, the differences were minor, and the 2 methods showed good correlation. As confirmed in this study, DN T (%) estimated by the 2-color method is lower than the actual value. We suggest that although the 2 methods can be used interchangeably, the 4-color method is recommended for the analysis of some specific subpopulations such as DN T (%).

Nodular lymphoid hyperplasia of the stomach in a patient with multiple submucosal tumors

Nodular lymphoid hyperplasia of the stomach is a rare lymphoproliferative disorder. Here, we report a 38-year-old man who presented with multiple submucosal tumors of the stomach. Histologically, the lesions were characterized by multiple discrete submucosal nodules of lymphoid cells. The infiltrates between the lymphoid follicles were composed mainly of medium-sized lymphoid cells with abundant clear cytoplasm, as well as a few large cells with vesicular nuclei. The gastric mucosa exhibited multifocal lymphoid aggregates and some of the epithelial cells were infiltrated by small lymphocytes mimicking lymphoepithelial lesions. Histopathology was consistent with mucosa-associated lymphoid tissue lymphoma. However, the infiltrating lymphoid cells were positive for CD2, CD3, CD5, and CD7. In addition, polymerase chain reaction analysis of the immunoglobulin heavy chain and T-cell receptor gene rearrangements demonstrated polyclonality. This case was diagnosed as reactive lymphoid hyperplasia of the stomach.

Plasma cell leukemia with rouleaux formation involving neoplastic cells and RBC

No abstract available.

Current Status and Proposal of a Guideline for Manual Slide Review of Automated Complete Blood Cell Count and White Blood Cell Dfferential / 대한진단검사의학회지

BACKGROUND: Manual slide review (MSR) is usually triggered by the results of automated hematolgy analyzers, but each laboaratory has different ciriteria for MSR. This study was carried out to investigate the current status of MSR criteria of automated complete blood cell count (CBC) and white blood cell (WBC) differential results and to propose a basic guideline for MSR. METHODS: Total 111 laboratories were surveyed regarding MSR using questionnaires. The questionnaire asked: kinds of automated hematology analyzers used and the presence of criteria triggering MSR in seven categories: 1) CBC results, 2) 5 differential WBC counts, 3) 3 differential WBC counts, 4) automated reticulocyte counts, 5) delta check, 6) instrument flags (or messages), 7) clinical information (wards or diseases). Based on the survey results, we determined basic and extended criteria for MSR. With these criteria, we consulted nine hematology experts to get a consensus. RESULTS: All 111 laboratories had their own MSR criteria. Among 111 laboratories, 98 (88.3%) used more than three criteria for MSR including CBC results and 5-part WBC differential count results and 95 (85.6%) had criteria of flags triggering MSR. For MSR criteria with numeric values, the 10th, 50th, and 90th percentiles of upper and lower threshold values were obtained. The basic guideline for MSR was made. CONCLUSIONS: We proposed a basic guideline for MSR. This guideline would be helpful to hematology laboratories for their daily operation and providing more rapid and accurate CBC and WBC differential results.

Two Cases of Acute Myeloid Leukemia with t(16;21)(p11;q22) and TLS/FUS-ERG Fusion Transcripts / 대한진단검사의학회지

Many AML-associated chromosomal abnormalities, such as t(8;21), t(15;17), inv(16), t(9;11), t(9;22) and t(6;9) are well known. The chromosomal aberration of t(16;21)(p11;q22) in AML is rare and it is known to be associated with poor prognosis, young age (median age, 22 yr), and involvement of various subtypes of the French-American-British classification. We report here 2 AML patients with t(16;21)(p11;q22), proved by conventional cytogenetics and/or reverse transcription (RT)-PCR. Erythrophagocytosis by leukemic blasts was observed in both of the cases. One patient was a 24 yr-old male with acute myelomonocytic leukemia. His karyotype was 46,XY,t(16;21)(p11;q22),del(18)(p11.2) and RT-PCR revealed the TLS/FUS-ERG fusion transcripts. Although he received allogeneic peripheral blood stem cell transplantation after the first remission, he died 9 months after the initial diagnosis due to relapse of the disease and graft-versus-host disease. The other patient was a 72 yr-old male with acute myeloid leukemia without maturation. His karyotype was 45,XY,-16,add(21)(q22) and the presence of t(16;21)(p11;q22) was detected by RT-PCR. He was transferred to another hospital with no more follow-up. We suggest that the presence of t(16;21)(p11;q22) and/or TLS/FUS-ERG fusion transcripts has to be considered in cases of AML with erythrophagocytosis.

Clinical Significance of Co-expression of Aberrant Antigens in Acute Leukemia

BACKGROUND: Acute leukemias co-expressing myeloid and lymphoid antigens but does not meet the criteria for biphenotypic acute leukemia (BAL) is common, however its clinical significance is not fully defined. METHODS: In this study, clinical features of 68 co-expressing (myeloid and lymphoid) acute leukemias diagnosed between January 2000 and December 2006 were studied and compared with those of a control group of patients (pure AML or ALL). RESULTS: Age, gender, initial Lactate dehydrogenase (LDH) level and cytogenetics were not different between the co-expressing group and the control group. But, the initial bone marrow blast percent was significantly higher in the co-expressing group (70% vs. 54.5%, P=0.003). Fifty five percent (16/29) of ALL and 30% (52/172) of AML patients showed myeloid and lymphoid markers concomitantly. The lymphoid antigen positive AML (Ly+AML) patients showed significantly shorter survival rates than pure AML patients (4 year survival rate, 17.6% vs. 45.6%, P=0.002). However hematopoietic stem cell transplantation (HST) abrogated the difference (4 year survival rate, 54.7% vs. 50.6%, P=0.894). In ALL patients, survival rate was not affected by myeloid antigen co-expression (4 year survival rate 26.1% vs. 20%, P=0.954). CONCLUSION: Co-expression of lymphoid markers in AML should be regarded as a poor prognostic factor and more aggressive treatment such as HST should be considered.