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Objectives To evaluate the frequency and clinicopathologic characteristics of RUNX1 mutations, focusing on patients with acute myeloid leukemia not otherwise specified (AML NOS). Methods Diagnostic samples from 219 patients with AML NOS were analyzed for RUNX1 mutations using standard polymerase chain reaction and direct sequencing. Results Thirty-one RUNX1 mutations were detected in 33 (15.1%) patients. Mutations clustered in the Runt homology (61.3%) and transactivation domains (25.8%). Frameshift mutations were most common (51.6%), followed by missense (41.9%) and nonsense (6.5%) mutations. Patients with RUNX1 mutations had a lower platelet count (P = .013) and shorter relapse-free survival (P = .045) than those without. The presence of RUNX1 and NPM1 or CEBPA mutations was mutually exclusive. A literature review, including our study, showed that patients with RUNX1 mutations were associated with intermediate risk; coexisting mutations such as FLT3-ITD, ASXL1, TET2, and DNMT3A; and a relatively cytogenetic heterogeneity. Conclusions Our findings strengthen previous data concerning RUNX1 mutations in AML and support the notion that RUNX1 mutational status should be integrated into a diagnostic workup of AML, particularly for AML NOS or an intermediate-risk group.

Objectives: Current guidelines recommend the eosin-5′-maleimide (EMA) binding test and cryohemolysis test for screening for hereditary spherocytosis (HS), and the flow cytometric osmotic fragility (FC OF) test was recently developed to replace the classic OF test. We evaluatedthe performance of the EMA binding test, FC OF test, cryohemolysis test, and the hemoglobin (Hb)/mean corpuscular hemoglobin concentration (MCHC) ratio in the diagnosis of HS and assessed whether these tests reflect the clinical severity of HS. Methods: A total of 153 patients with anemia (33 with HS, 40 with autoimmune hemolytic anemia, 40 with anemia of chronic disease, and 40 with iron deficiency anemia [IDA]) and 140 healthy controls were enrolled, and the performance of the three tests was evaluated. Results: Both the EMA binding test (area under the curve [AUC], 0.996) and the FC OF test (AUC, 0.992) performed satisfactorily, but the cryohemolysis test (AUC, 0.723) performed significantly worse because of false positivity in patients with IDA. The Hb/MCHC ratio ( P < .001) was able to reflect the clinical severity of HS. Conclusions: Our results demonstrate that both the EMA binding and FC OF tests are useful as screening tests for the diagnosis of HS, but the cryohemolysis test has limited use due to its false positivity in IDA, with the Hb/MCHC ratio the most useful parameter for assessing the clinical severity of HS.

Objectives: To explore posttransplant lymphoproliferative disorder (PTLD) cases associated with Epstein-Barr virus (EBV). Methods: We retrospectively reviewed the EBV DNA quantitation data of 9,779 blood samples from 740 transplant patients and their associations with PTLD. Results: EBV viremia occurred more frequently in patients with PTLD (85.4%) in comparison with patients without PTLD (38.3%; P < .0001). Patients with PTLD demonstrated significantly higher first positive results, higher peak levels, and a higher rate of increase in EBV viral load compared with patients without PTLD ( P = .002, P < .0001, and P < .0001, respectively). However, in the multivariate analysis, only the peak level was associated with the development of PTLD. In particular, within hematopoietic stem cell recipients, the peak level able to diagnose PTLD was an area under the receiver operating characteristic curve of 0.806. Conclusions: We believe that pattern analysis of EBV DNA quantitation results could lead to the early diagnosis and timely treatment of PTLD.

We previously reported 24 cases of marrow fibrin-ring granuloma (FRG) encountered in 1 institution and concluded that, contrary to previous studies showing marrow FRG as a diagnostic marker for Q fever, Epstein-Barr virus (EBV) was the most common proven cause of such FRG. The present study characterized patients with EBV-associated marrow FRG. We retrospectively reviewed 17 cases of EBV-associated FRG (43% of 40 cases with marrow FRG) diagnosed by bone marrow biopsy. Patients with EBV-associated hemophagocytic lymphohistiocytosis (5/17 patients) and chronic active EBV infection (4/17) constituted 53% of patients with EBV-associated FRG. Three patients had lymphoma without marrow involvement. All patients except 1 presented first with fever; splenomegaly was the next most common clinical finding (12/17). Cytopenia was observed in the 17 cases: anemia in 16, thrombocytopenia in 9, and leukopenia in 8. Patients with EBV-associated FRG showed lower survival outcomes than did patients without EBV (median, 3.0 vs 11.8 months; P = .009). Patients with bone marrow FRG accompanied by fever require careful evaluation to discern whether active EBV infection is involved because the prognosis is poor.

We retrospectively reviewed the clinical and laboratory data and bone marrow (BM) histomorphologic features in 33 angioimmunoblastic T-cell lymphoma (AITL) cases. Paraffin-embedded BM core biopsy specimens were reacted immunohistochemically with antibodies to pan–T-cell markers, CD20, CD10, CD21, and bcl-6. The frequency of BM involvement was 70% (23/33). The following features were more significant in patients with than without BM involvement: fever, hepatosplenomegaly, pleural effusion, elevated lactate dehydrogenase level, hypoalbuminemia, hyponatremia, hypocalcemia, anemia, circulating atypical cells, hypercellular marrow, and plasmacytosis in the BM. Morphologic features included nodular or interstitial infiltration in a paratrabecular distribution, periodic acid–Schiff–positive intercellular materials, mixed infiltrates of T and B cells, presence of clear cells, and blood vessel proliferation. Immunohistochemical assays revealed that CD5, bcl-6, and CD10 were useful markers of BM infiltration. Seven cases with BM involvement were interpreted as negative for lymphoma initially, mainly owing to insufficient information in nodal biopsy specimens. Several clinical and laboratory features indicate BM involvement of AITL at diagnosis. Laboratory physicians should be more familiar with BM histomorphologic and immunophenotypic characteristics suggesting AITL infiltration to make accurate diagnoses even without prior nodal biopsies.

Objectives: We developed and validated an interinstrument comparison method for automatic hematology analyzers based on the 99th percentile coefficient of variation (CV) cutoff of daily means and validated in both patient samples and quality control (QC) materials. Methods: A total of 120 patient samples were obtained over 6 months. Data from the first 3 months were used to determine 99th percentile CV cutoff values, and data obtained in the last 3 months were used to calculate acceptable ranges and rejection rates. Identical analyses were also performed using QC materials. Two instrument comparisons were also performed, and the most appropriate allowable total error (ATE) values were determined. Results: The rejection rates based on the 99th percentile cutoff values were within 10.00% and 9.30% for the patient samples and QC materials, respectively. The acceptable ranges of QC materials based on the currently used method were wider than those calculated from the 99th percentile CV cutoff values in most items. In two-instrument comparisons, 34.8% of all comparisons failed, and 87.0% of failed comparisons were successful when 4 SD was applied as an ATE value instead of 3 SD. Conclusions: The 99th percentile CV cutoff value–derived daily acceptable ranges can be used as a real-time interinstrument comparison method in both patient samples and QC materials. Applying 4 SD as an ATE value can significantly reduce unnecessarily followed recalibration in the leukocyte differential counts, reticulocytes, and mean corpuscular volume.

We compared the TEST 1 (Alifax, Padova, Italy) and Westergren methods of measuring the erythrocyte sedimentation rate (ESR) to assess inflammation. The ESR was measured by both methods in 154 blood samples from patients with malignancy (n = 69), autoimmune disease (n = 44), or infection (n = 41). Total protein, albumin, and C-reactive protein (CRP) levels were measured in each plasma sample, and albumin and α1-, α2-, β1-, β2-, and γ-globulin fractions were measured by capillary electrophoresis. TEST 1 ESR values were significantly lower than the Westergren values, by 10.9 mm/h. We found that the correlations of TEST 1 ESR values with inflammatory protein levels (total protein, globulin, CRP, and α1-, α2-, β2-, and γ-globulin) were better than those obtained using the Westergren method. These findings indicate that ESR measurements by TEST 1 reflect inflammation better than do those by the Westergren method in patients with malignancy, autoimmune disease, or infection.