Evaluation of laboratory diagnostic tests for light-chain clonality and bone marrow findings in AL amyloidosis

Background@#Light-chain amyloidosis (AL) is the most common form of systemic amyloidosis. This study aimed to evaluate the usefulness of laboratory tests for light-chain clonality and bone marrow (BM) findings in AL amyloidosis. @*Methods@#We retrospectively enrolled patients newly diagnosed with AL amyloidosis on pathological examination who underwent a BM biopsy. Laboratory test data for light-chain clonality were collected and compared. Amyloid deposits were identified with H&E, Congo red, and PAS stains. @*Results@#We reviewed 98 patients with AL amyloidosis. Light chain clonality (λ, 64 cases; κ, 34 cases) was detected by serum immunofixation electrophoresis (IFE) (63.3%), urine IFE (70.8%), serum protein electrophoresis (PEP) (44.9%), urine PEP (44.8%), serum free light chain (SFLC) ratio (79.5%), and BM immunohistochemistry (IHC) (85.7%). Flow cytometric (FCM) assay identified aberrant BM plasma cells in 92.9% of cases. BM amyloid deposits were identified in 35 of the 98 cases (35.7%); 71.4% (25/35) were Congo red-positive, and 100.0% (35/35) were PAS-positive. @*Conclusion@#Laboratory tests for detecting light-chain clonality in AL amyloidosis in order of sensitivity include FCM assay for aberrant plasma cells, IHC for light chains on BM biopsy or clot section, SFLC ratio, and serum and urine IFE. Congo red staining of BM samples remains an important tool for identifying amyloid deposits in BM. Periodic acid-Schiff (PAS) staining can be useful in diagnosing some cases of Congo red-negative amyloidosis.

Immune Checkpoint Programmed Cell Death Protein-1 (PD-1) Expression on Bone Marrow T Cell Subsets in Patients With Plasma Cell Myeloma

Background@#Plasma cell myeloma (PCM) is caused by immune dysregulation. We evaluated the expression of immune checkpoint programmed cell death protein-1 (PD-1) on T cell subsets in PCM patients according to disease course and cytogenetic abnormalities.This study aimed to find a target group suitable for therapeutic use of PD-1 blockade in PCM. @*Methods@#A total of 188 bone marrow (BM) samples from 166 PCM patients and 32 controls were prospectively collected between May 2016 and May 2017. PD-1 expression on BM T cell subsets was measured using flow cytometry. @*Results@#At diagnosis, the median PD-1 expression on CD4+ T cells was 24.6%, which did not significantly differ from that in controls. After stem cell transplantation, PD-1 expression on CD4+ T cells was higher than that at diagnosis (P < 0.001), regardless of residual disease. PD-1 expression on CD4+ T cells in patients with residual disease after chemotherapy was significantly higher than that at diagnosis (P = 0.001) and after complete remission following chemotherapy (P = 0.044). PD-1 expression on CD8+ T cells was higher in PCM patients with cytogenetic abnormalities, including monosomy 13, 1q gain, complex karyotype, and hypodiploidy. @*Conclusions@#PD-1 blockade might have therapeutic potential in refractory PCM patients after chemotherapy, especially in those with high- or intermediate-risk cytogenetic abnormalities.

JL1 Antigen Expression on Bone Marrow Lymphoma Cells from Patients With Non-Hodgkin Lymphoma

BACKGROUND: JL1, a CD43 epitope and mucin family cell surface glycoprotein, is expressed on leukemic cells. An anti-JL1 antibody combined with a toxic substance can have targeted therapeutic effects against JL1-positive leukemia; however, JL1 expression on bone marrow (BM) lymphoma cells has not been assessed using flow cytometry. We investigated JL1 expression on BM lymphoma cells from patients with non-Hodgkin lymphoma (NHL) to assess the potential of JL1 as a therapeutic target. METHODS: Patients with BM involvement of mature B-cell (N=44) or T- and natural killer (NK)-cell (N=4) lymphomas were enrolled from May 2015 to September 2016. JL1 expression on BM lymphoma cells was investigated using flow cytometry. Clinical, pathological, and cytogenetic characteristics, and treatment responses were compared according to JL1 expression status. RESULTS: Of the patients with NHL and BM involvement, 37.5% (18/48) were JL1-positive. Among mature B-cell lymphomas, 100%, 38.9%, 33.3%, 100%, and 25.0% of Burkitt lymphomas, diffuse large B-cell leukemias, mantle cell leukemias, Waldenstrom macroglobulinemia, and other B-cell lymphomas, respectively, were JL1-positive. Three mature T- and NK-cell NHLs were JL1-positive. JL1 expression was associated with age (P=0.045), complete response (P=0.004), and BM involvement at follow-up (P=0.017), but not with sex, performance status, the B symptoms, packed marrow pattern, cytogenetic abnormalities, or survival. CONCLUSIONS: JL1 positivity was associated with superior complete response and less BM involvement in NHL following chemotherapy.

First Case of Double T-Cell Receptor Alpha/Delta Rearrangements of t(11;14) and inv(14) and Subsequent JAK2 Rearrangement in a Patient With T-cell Acute Lymphoblastic Leukemia

No abstract available.

The First Korean Case of Epstein-Barr Virus-positive Natural Killer/T-cell Lymphoma That Progressed From Severe Mosquito Bite Allergy, With Coexistence of Hemophagocytic Lymphohistiocytosis

No abstract available.

Revision of Laboratory Testing Guidelines for Initial Diagnosis of Hematologic Neoplasms

Performance Evaluation of the CS-5100 Coagulation Analyzer for Special Coagulation Parameters

Clinical, Laboratory, and Bone Marrow Findings of 31 Patients With Waldenström Macroglobulinemia

BACKGROUND: Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma (LPL) with bone marrow (BM) involvement and an IgM monoclonal gammopathy of any level. We aimed to identify the clinical, laboratory, and BM findings of patients with WM and to evaluate the usefulness of CD154 for the diagnosis and prognosis of WM.METHODS: We reviewed the medical records and BM studies and/or flow cytometric immunotyping of 31 patients with untreated WM. Semiquantitative immunohistochemistry (CD20, CD138, tryptase, and CD154) of BM was performed.RESULTS: Only six patients presented with symptoms of hyperviscosity syndrome. Eleven patients had solid cancer and/or another hematologic malignancy. Mast cells (MC) increased in all samples, with some in close contact with tumor cells. Tryptase-positive MC (17.1/ high-power fields [HPF], 1.2–72.0/HPF) and CD154-positive MC (8.6/HPF, 0.1–31.1/HPF) were observed. The high CD154-positive MC (≥8.6/HPF) group showed a lower overall five-year survival rate than the low CD154-positive MC (<8.6/HPF) group (71.9% vs. 100.0%; P=0.012). Flow cytometric immunophenotyping of BM aspirates showed increased B lymphocytes and plasma cells with a normal phenotype (CD138⁺/CD38⁺/CD19⁺/CD45⁺/CD56⁻).CONCLUSIONS: Approximately one third of WM patients showed other malignancies and all patients had increased MC. Immunohistochemistry and flow cytometric immunophenotyping are useful for diagnosing WM, and increased CD154-positive MC can indicate poor prognosis.

POEMS Syndrome: Bone Marrow, Laboratory, and Clinical Findings in 24 Korean Patients

POEMS syndrome is a rare paraneoplastic syndrome, which includes polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes due to plasma cell (PC) neoplasm. Diagnosis of this disease is challenging because of its rarity and complex clinical manifestations. We attempted to identify the key clinical features and characteristic bone marrow (BM) findings of POEMS syndrome, by reviewing the medical records and BM analyses of 24 Korean patients. Frequent clinical manifestations included polyneuropathy (100%), monoclonal gammopathy (100%), organomegaly (92%), extravascular volume overload (79%), and endocrinopathy (63%). The BM analyses revealed mild PC hyperplasia (median PCs: 5.5%) and frequent megakaryocytic hyperplasia (88%), megakaryocyte clusters (88%), and hyperlobation (100%). Flow cytometry of BM aspirates using CD138/CD38/CD45/CD19/CD56 showed normal (67%, 4/6) or neoplastic PC immunophenotypes (33%, 2/6). A diagnosis of POEMS syndrome must be considered when a patient suspected of having PC dyscrasia shows the above clinical presentation and BM findings.

Two Rare Cases of Therapy-Related Acute Lymphoblastic Leukemia in Patients With Plasma Cell Myeloma

No abstract available.

Recommendation for the Peripheral Blood Cell Morphology Report

There is considerable heterogeneity in the peripheral blood smear reports across different diagnostic laboratories, despite following the guidelines published by the International Council for Standardization in Haematology (ICSH). As standardization of reports can facilitate communication and consequently the diagnostic efficiency in both laboratories and clinics, the standardization committee of the Korean Society for Laboratory Hematology aimed to establish a detailed guideline for the standardization of peripheral blood smear reports. Based on the ICSH guidelines, additional issues on describing and grading the peripheral blood smear findings were discussed. In this report, the proposed guideline is briefly described.

Unique Red Blood Cell Morphology Detected in a Patient with Myelodysplastic Syndrome by Three-dimensional Refractive Index Tomography

The three-dimensional (3-D) shape of erythrocytes is strongly associated with various diseases. However, conventional optical imaging approaches with Wright's staining only provide information on two-dimensional morphology. Here, we employed optical diffraction tomography (ODT), a label-free 3-D quantitative phase imaging technique, and observed uniquely shaped red blood cells (RBCs) in the peripheral blood of a patient diagnosed with myelodysplastic syndrome. Peripheral blood samples were collected when the patient visited our hospital for his two out-patient follow-ups in May 2018. The 3-D tomograms of randomly chosen RBCs were reconstructed using a commercial ODT setup. From the reconstructed 3-D RBCs, 37.5% and 32.8% of RBCs demonstrated cup-like shapes at the first and the second out-patient follow-up, respectively. Even though this is a single case report, the finding is novel and can be a potential dyserythropoietic feature found in peripheral blood.

Is it possible to reduce intra-hospital transport time for computed tomography evaluation in critically ill cases using the Easy Tube Arrange Device?

OBJECTIVE: Patients are often transported within the hospital, especially in cases of critical illness for which computed tomography (CT) is performed. Since increased transport time increases the risks of complications, reducing transport time is important for patient safety. This study aimed to evaluate the ability of our newly invented device, the Easy Tube Arrange Device (ETAD), to reduce transport time for CT evaluation in cases of critical illness. METHODS: This prospective randomized control study included 60 volunteers. Each participant arranged five or six intravenous fluid lines, monitoring lines (noninvasive blood pressure, electrocardiography, central venous pressure, arterial catheter), and therapeutic equipment (O2 supply device, Foley catheter) on a Resusci Anne mannequin. We measured transport time for the CT evaluation by using conventional and ETAD method. RESULTS: The median transport time for CT evaluation was 488.50 seconds (95% confidence interval [CI], 462.75 to 514.75) and, 503.50 seconds (95% CI, 489.50 to 526.75) with 5 and 6 fluid lines using the conventional method and 364.50 seconds (95% CI, 335.00 to 388.75), and 363.50 seconds (95% CI, 331.75 to 377.75) with ETAD (all P < 0.001). The time differences were 131.50 (95% CI, 89.25 to 174.50) and 148.00 (95% CI, 116.00 to 177.75) (all P < 0.001). CONCLUSION: The transport time for CT evaluation was reduced using the ETAD, which would be expected to reduce the complications that may occur during transport in cases of critical illness.

Clinical and Cytogenetic Profiles of Rhabdomyosarcoma with Bone Marrow Involvement in Korean Children: A 15-Year Single-Institution Experience

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Alveolar RMS (ARMS) is characterized by FOXO1-related chromosomal translocations that result in a poorer clinical outcome compared with embryonal RMS (ERMS). Because the chromosomal features of RMS have not been comprehensively defined, we analyzed the clinical and laboratory data of childhood RMS patients and determined the clinical significance of chromosomal abnormalities in the bone marrow. METHODS: Fifty-one Korean patients with RMS < 18 years of age treated between 2001 and 2015 were enrolled in this study. Clinical factors, bone marrow and cytogenetic results, and overall survival (OS) were analyzed. RESULTS: In total, 36 patients (70.6%) had ERMS and 15 (29.4%) had ARMS; 80% of the ARMS patients had stage IV disease. The incidences of bone and bone marrow metastases were 21.6% and 19.6%, respectively, and these results were higher than previously reported results. Of the 40 patients who underwent bone marrow cytogenetic investigation, five patients had chromosomal abnormalities associated with the 13q14 rearrangement. Patients with a chromosomal abnormality (15 vs 61 months, P=0.037) and bone marrow involvement (17 vs 61 months, P=0.033) had a significantly shorter median OS than those without such characteristics. Two novel rearrangements associated with the 13q14 locus were detected. One patient with concomitant MYCN amplification and PAX3/FOXO1 fusion showed an aggressive clinical course. CONCLUSIONS: A comprehensive approach involving conventional cytogenetics and FOXO1 FISH of the bone marrow is needed to assess high-risk ARMS patients and identify novel cytogenetic findings.

Bone Marrow Involvement of Epstein-Barr Virus-Positive Large B-Cell Lymphoma in a Patient with Angioimmunoblastic T-Cell Lymphoma

No abstract available.

A Case of Acute Myeloid Leukemia Concurrent With Untreated Chronic Lymphocytic Leukemia

No abstract available.

Is the Modified AIMS65 Score Suitable for Distinguishing the Low Risk Group and the High Risk Group for Patients with Upper Gastrointestinal Bleeding?

PURPOSE: The goal of this study was to increase the performance of the AIMS65 score in the prediction of outcomes in upper gastrointestinal bleeding by modifying the AIMS65 score. METHODS: Data were collected retrospectively between January 2015 and June 2015. A total of 212 adult patients, who visited the emergency department with an upper gastrointestinal hemorrhage during this period were included for analysis. High risk patients were defined as follows: those who needed an endoscopic or surgical hemostasis, suffered rebleeding, hospitalized in an intensive care unit, and those who were deceased within 30 days or required a blood transfusion. The seven parameters of the modified AIMS65 score were as follows: Albumin levels, international normalized ratio (prothrombin time), altered mental status, systolic blood pressure, age>65 years, hemoglobin levels, and heart rate. RESULTS: The high-risk group was comprised of 163 patients, while the low risk group was comprised of 49 patients. The areas under the curve for AIMS65 and modified AIMS65 scores were 0.727 (95% confidence interval, 0.662-0.786) and 0.847 (95% confidence interval, 0.791-0.892), respectively, which were significantly different (p<0.001). The AIMS65 score had a sensitivity of 53.0% and a specificity of 78.5% at a score of 0. The modified AIMS65 score had a sensitivity of 22.4% and a specificity of 99.3% at a score of 0. For the modified AIMS65 score of 3 or lower, the sensitivity was 97.9% with a specificity of 21.4%. CONCLUSION: The modified AIMS65 score was effective in distinguishing between the low-risk group and the high-risk group among patients with upper gastrointestinal bleeding.

Frequency and Distinct Characteristics of Acute Myeloid Leukemia Lacking HLA-DR and CD34 Expression: Features Intermediate between Typical Acute Myeloid Leukemia and Acute Promyelocytic Leukemia

BACKGROUND: The objective of this study was to investigate the frequency and characteristics of HLA-DR⁻/CD34⁻ acute myeloid leukemia (AML) also known as acute promyelocytic leukemia (APL)-like AML. METHODS: This study included 683 newly diagnosed patients with AML. After exclusion of 211 patients with recurrent genetic abnormalities, one with acute panmyelosis with myelofibrosis, two with myeloid leukemia associated with Down syndrome, and two devoid of metaphase cells, we classified the remaining 467 patients as follows: group 1, HLA-DR⁺/CD34⁺ (typical AML); group 2, HLA-DR⁺/CD34⁻ or HLA-DR⁻/CD34⁺; group 3, APL-like AML. RESULTS: Group 1 comprised 294 patients, group 2 comprised 133, and group 3 comprised 40. Therefore, the frequency of APL-like AML among 683 unselected patients with AML was 5.9%. Group 3 patients had significantly higher leukocyte counts and bone marrow (BM) blast percentages, higher frequencies of normal karyotypes and NPM1 mutation, higher fractions of CD33-positive cells, higher concentrations of fibrin degradation products and D-dimers, lower frequencies of complex karyotypes, monosomal karyotypes and poor cytogenetic risk, lower fractions of CD13-positive cells, and lower fibrinogen concentrations, compared with group 1 patients. The values of the BM blast percentage, number of CD33-positive cells, and DIC score of the patients with APL-like AML were intermediate between those of the patients with typical AML and APL. CONCLUSIONS: This study demonstrates that APL-like AML is not uncommon, and it has characteristics distinguishable from those of typical AML. APL-like AML may have some pathophysiological relationships with APL, which need further investigation.

A Case of Primary Bone Marrow Diffuse Large B-cell Lymphoma Presenting With Fibrillar Projections and Hemophagocytic Lymphohistiocytosis

No abstract available.

The First Case of Therapy-Related Myelomastocytic Leukemia Based on the WHO 2008 Classification and the Recently Proposed Diagnostic Criteria

No abstract available.