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Annals of laboratory medicine. 05/2013; 33(3):229-32.
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ABSTRACT: Bone marrow involvement confers a poor prognosis in patients with diffuse, large, B-cell lymphoma (DLBCL). However, the prognostic significance of concordant and discordant bone marrow involvement in these cases differs. We analysed this further in patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) at a single institute.
The cytomorphology of bone marrow involvement was evaluated in 632 patients who were diagnosed with DLBCL in primary tissues and had received R-CHOP therapy. Bone marrow trephine biopsies and clot sections were analysed, along with the immunohistochemical analysis of CD20, CD79a and CD3.
Bone marrow involvement was identified in 80 of our DLBCL patient subjects (12.7%). Of these, 32 (40%) showed discordant bone marrow involvement, and 48 (60%) showed concordant involvement. Kaplan-Meier survival analysis showed that progression-free survival and overall survival was poorer in the concordant group (p<0.001). Multivariate analysis, adjusted for the International Prognostic Index score, showed that concordant involvement was an independent predictor of progression-free survival (p<0.001) and overall survival (p=0.011). Discordant involvement was not a negative prognostic factor independent of the International Prognostic Index.
Prognostication based on bone marrow involvement cytomorphology is a useful indicator of progression-free survival and overall survival, independent of the International Prognostic Index score, in DLBCL patients. Accurate staging based on morphology should thus be included in bone marrow examinations of such cases.
Journal of clinical pathology 05/2013; 66(5):420-5. · 2.43 Impact Factor
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ABSTRACT: We report here a case of a 59-yr-old man with CD4(+) T-cell large granular lymphocytic leukemia (T-LGL). Peripheral blood examination indicated leukocytosis (45×10(9) cells/L) that consisted of 34% neoplastic lymphoid cells. Other laboratory results indicated no specific abnormalities except for serum antinuclear antibody titer (1:640), glucose (1.39 g/L), and hemoglobin A1c (7.7%) levels. Computed tomography indicated multiple small enlarged lymph nodes (<1 cm in diameter) in both the axillary and inguinal areas, a cutaneous nodule (1.5 cm in diameter) in the left suboccipital area, and mild hepatosplenomegaly. Bone marrow examination revealed hypercellular marrow that consisted of 2.4% neoplastic lymphoid cells. The neoplastic lymphoid cells exhibited a medium size, irregularly shaped nuclei, a moderate amount of cytoplasm, and large granules in the cytoplasm. Immunohistochemical analysis indicated CD3(+), CD4(+), T-cell receptor βF1(+), granzyme B(+), and TIA1(+). Flow cytometric analysis of the neoplastic lymphoid cells revealed CD3+, cytoplasmic CD3(+), CD4(+), and CD7(+). Cytogenetic analysis indicated an abnormal karyotype of 46,XY,inv(3)(p21q27),t(12;17)(q24.1;q21),del(13)(q14q22)[2]/46,XY[28]. The patient was diagnosed with CD4(+) T-LGL and received chemotherapy (10.0 mg methotrexate). This is the second case of CD4(+) T-LGL that has been reported in Korea.
Annals of laboratory medicine. 05/2013; 33(3):196-9.
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Annals of Hematology 04/2013; · 2.62 Impact Factor
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ABSTRACT: Multiparametric flow cytometry (MFC) allows discrimination between normal and neoplastic plasma cells (NeoPCs) within the bone marrow plasma cell (BMPC) compartment. This study sought to characterize immunophenotypes and quantitate the proportion of NeoPCs in BMPCs to diagnose plasma cell myeoma (PCM) and evaluate the prognostic impact of this method. We analyzed the MFC data of the bone marrow aspirates of 76 patients with PCM and 33 patients with reactive plasmacytosis. MFC analysis was performed using three combinations: CD38/CD138/-/CD45; CD56/CD20/CD138/CD19; and CD27/CD28/CD138/CD117. The plasma cells of patients with reactive plasmacytosis demonstrated normal immunophenotypic patterns. Aberrant marker expression was observed in NeoPCs, with negative CD19 expression observed in 100% of cases, CD56+ in 73.7%, CD117+ in 15.2%, CD27- in 10.5%, CD20+ in 9.2%, and CD28+ in 1.3%. In PCM patients, more than 20% of NeoPCs/BMPCs were significantly associated with factors suggestive of poor clinical outcomes. Patients who were CD27- or CD56+/CD27-, demonstrated shorter overall survival than patients of other CD56/CD27 combinations. Our results support the clinical value of immunophenotyping and quantifying NeoPCs in PCM patients. This strategy could help to reveal poor prognostic categories and delineate surrogate markers for risk stratification in PCM patients.
Journal of Korean medical science 04/2013; 28(4):542-9. · 0.84 Impact Factor
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ABSTRACT: AIMS: The immunohistopathological features of lesions involving the bone marrow (BM) were examined in patients with anaplastic large-cell lymphoma (ALCL) to identify the most useful markers for the detection of BM involvement in ALCL. METHODS AND RESULTS: A total of 80 patients with ALCL were enrolled, of whom 15 (18.8%) showed BM involvement. Anaplastic lymphoma kinase-negative (ALK-) patients (n = 11) showed a nodular BM involvement pattern more frequently than ALK+ patients (n = 4; 72.7% versus 25.0%, P = 0.095). Patients with interstitial BM involvement were more frequently ALK+ than those with nodular BM involvement (50.0% versus 11.1%, P = 0.095). CD30 positivity was the strongest indicator of the presence of BM lesions, regardless of the BM involvement pattern. The application of CD30 in cases without morphological evidence of BM involvement detected subtle BM involvement by ALCL in 13.7% of cases, which were predominantly ALK+. CONCLUSIONS: The immunohistopathological features of BM lesions in patients with ALCL differ according to ALK status and BM involvement pattern. CD30 is the most useful marker for the identification of BM lesions in ALCL patients and should be employed in all ALCL patients without exception, especially ALK+ cases.
Histopathology 03/2013; · 3.08 Impact Factor
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ABSTRACT: The aim of this study was to evaluate effect of c-KIT mutations on RUNX1/RUNX1T1 fusion transcript expression in patients with t(8;21)-positive AML. Fifty patients diagnosed with t(8;21)-positive AML for recent 10 years were enrolled. Patients with c-KIT mutations tended to achieve a greater than 3-log reduction in RUNX1/RUNX1T1 fusion transcript expression less frequently than patients without mutations from 6 to 12 months of follow-up. They have difficulties to obtain molecular complete remission and experience molecular relapse more frequently and rapidly than those without mutations. These results support poor prognostic impact of c-KIT mutations in t(8;21)-positive AML.
Leukemia research 03/2013; · 2.36 Impact Factor
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Clinical Chemistry and Laboratory Medicine 03/2013; · 2.15 Impact Factor
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ABSTRACT: In up to 40% of systemic mastocytosis (SM) cases, an associated clonal hematological non-mast cell lineage disease such as AML is diagnosed before, simultaneously with, or after the diagnosis of SM. A 40-yr-old man was diagnosed with AML with t(8;21)(q22;q22). Mast cells were not noted at diagnosis, but appeared as immature forms at relapse. After allogeneic hematopoietic stem cell transplantation (HSCT), leukemic myeloblasts were not observed; however, neoplastic metachromatic blasts strikingly proliferated during the state of bone marrow aplasia, and finally, aleukemic mast cell leukemia developed. As the disease progressed, we observed serial morphologic changes from immature mast cells with myeloblasts to only metachromatic blasts and atypical mast cells as mast cell leukemia; FISH analysis showed that the neoplastic mast cells originated from the same clone as the leukemic myeloblasts of AML.
Annals of laboratory medicine. 03/2013; 33(2):125-129.
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ABSTRACT: The prognostic impact of the presence of differentiating neuroblasts in bone marrow (BM) remains unclear in BM metastatic neuroblastoma (NB). We aimed to identify the prognostic impact of differentiating neuroblasts in BM at diagnosis and after chemotherapy.
A total of 51 patients diagnosed with BM metastatic NB at Asan Medical Center between January 1990 and July 2005 were enrolled. BM histology and laboratory data along with overall survival (OS) were compared with regard to the differentiation status of neuroblasts in BM at diagnosis and after chemotherapy.
Among the 51 patients, 13 (25.5%) exhibited differentiating neuroblasts in BM at diagnosis and 17/51 (33.3%) exhibited them after chemotherapy. The only significant difference among patient groups was the improved OS in patients with differentiated neuroblasts in BM at diagnosis (P=0.021). In contrast, the differentiation status of neuroblasts in BM after chemotherapy did not affect OS (P=0.852).
Our study is the first report describing the presence of differentiating neuroblasts in BM. The presence of differentiating neuroblasts in BM at diagnosis may be a favorable prognostic factor for patients with BM metastatic NB; however, the same phenomenon after chemotherapy is irrelevant to prognosis.
Annals of laboratory medicine. 03/2013; 33(2):89-96.
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ABSTRACT: We evaluated the outcome of children and adolescents with acquired severe aplastic anemia (SAA) who received haploidentical hematopoietic stem cell transplantation (HHCT) within vitro T cell-depleted peripheral blood stem cells. Twelve patients with acquired SAA received a total of 15 HHCTs within vitro CD3-depleted grafts between July, 2009, and July, 2012. Among the 12 patients, 11 achieved neutrophil engraftment at a median of 10 days (range, 9-13 days) after HHCT. One patient failed to achieve primary engraftment and two experienced graft rejection soon after engraftment. All three patients who experienced early graft failure (GF) received a second HHCT and achieved sustained engraftment. Thus, the final engraftment rate was 100%. Acute graft versus host disease (aGVHD) was assessed in nine patients, excluding the three patients with early GF. Three of these patients developed aGVHD (two ≥ grade II and one with grade III). All 12 patients survived and were transfusion-independent at a median follow-up of 14.3 months (range, 4.1-40.7 months). Hematopoietic stem cell transplantation from haploidentical family donors with in vitro CD3 T cell depletion is a reasonable therapeutic option for children/adolescents with acquired SAA. Our future trial with a uniform protocol will help to solve the problems associated with HHCT and provide a valuable platform for the further development of HHCT as a therapy for SAA.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2013; · 3.15 Impact Factor
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ABSTRACT: Acute promyelocytic leukemia is characterized by the rearrangement of the retinoic acid receptor alpha (RARA) gene and its fusion with other genes. We report a novel case of variant acute promyelocytic leukemia with the karyotype der(2)t(2;17)(q32;q21). Array comparative genomic hybridization revealed distinct chromosome breakpoints within the RARA and oligonucleotide/oligosaccharide-binding fold containing 2A (OBFC2A) genes. Sequence analysis of the OBFC2A/RARA transcript showed that exon 5 of OBFC2A was fused with exon 3 of RARA through the same breakpoint as in previously described fusions of RARA. The single-stranded DNA binding protein encoded by OBFC2A is critical for genomic stability. Retention of the OB fold domain of OBFC2A in the fusion protein suggests the possibility of homodimerization. The leukemic cells from the patient showed neutrophilic differentiation in the in vitro all-trans retinoic acid assay. Mutation or rearrangement of the OBFC2A gene has not been previously reported in congenital or acquired disorders.
Blood 01/2013; · 9.90 Impact Factor
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Annals of laboratory medicine. 01/2013; 33(1):80-3.
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ABSTRACT: The recently developed Cytodiff flow cytometric system (Beckman Coulter, Miami, FL) enables leukocyte analysis using a single immunophenotyping panel tube composed of six markers and five colors and that can detect 16 leukocyte subpopulations. We performed a preliminary investigation of whether changes in any of 16 leukocyte differentials were associated with survival and treatment outcomes in patients with metastatic carcinoma or not. We measured 16 leukocyte differential counts using the Cytodiff flow cytometric system in peripheral blood samples from 40 patients with metastatic malignancy (27 stomach cancer and 13 lung cancer) before chemotherapy and at 15 day intervals after chemotherapy for 2 months. A higher percentage of CD16+ cytotoxic NK+T lymphocytes was found to be the only significant prognostic factor among by Cox regression analysis and a higher percentage of CD16+ cytotoxic NK+T lymphocytes (>5.0%) showed significantly longer survival outcomes by Kaplan-Meier analysis (P = 0.003). The Cytodiff system enables 16 leukocyte subpopulations in a one tube assay and also can operate with only small amounts of sample, although it cannot differentiate NK cells from T lymphocytes. Hence, the monitoring of all leukocyte subpopulations using Cytodiff flow cytometry may be a helpful prognostic tool for patients with metastatic carcinoma. © 2012 International Society for Advancement of Cytometry.
Cytometry Part B Clinical Cytometry 12/2012; · 2.53 Impact Factor
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Clinical Chemistry and Laboratory Medicine 12/2012; · 2.15 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the correlation of mutations of the fms-like tyrosine kinase (FLT3) and nucleophosmin (NPM1) genes with the cup-like nuclear morphology of blasts in patients with acute myeloid leukemia (AML). We retrospectively reviewed peripheral blood (PB) and bone marrow (BM) slides of 208 patients prepared at the time of diagnosis of AML based on the results of testing for mutations of both NPM1 exon 12 and FLT3. We investigated the association between this phenotype and hematologic findings, disease markers, and mutations in NPM1 exon 12, FLT3-internal tandem duplication (ITD), and tyrosine kinase domain (TKD) genes. Cup-like nuclei were found in 44 patients (21.2 %) diagnosed with AML. This morphology was associated with high blast counts in the PB and BM; AML type, especially AML M1 (FAB classification); low CD34 expression; and mutation of FLT3-ITD, -TKD, NPM1 regardless of other mutations (p < 0.05 for all). However, FLT3-ITD or TKD mutation alone (nine cases, p = 0.228) was not associated, and NPM1 mutation alone (14 cases, p = 0.036) was weakly associated with cup-like nuclei. Mutation of both NPM1 and FLT3-ITD or TKD (17 cases, p < 0.001) was strongly correlated with the cup-like nuclear morphology. AML with cup-like nuclei is strongly associated with co-occurring mutations of both NPM1 and FLT3-ITD or TKD. Therefore, testing for both mutations is recommended for patients with the cup-like nuclear morphology.
Annals of Hematology 12/2012; · 2.62 Impact Factor
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ABSTRACT: AIMS: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy derived from plasmacytoid dendritic cell precursors. Almost all patients show cutaneous manifestations, and >60% show bone marrow (BM) involvement at initial presentation. In cases where there is BM involvement by only a small number of tumour cells, such involvement is difficult to ascertain solely on morphological examination. In such situations, immunohistochemistry (IHC) may be useful in revealing minimal BM involvement by BPDCN. METHODS AND RESULTS: We investigated six patients with BPDCN. Initial morphological diagnosis disclosed BM involvement in only one of the six patients. To confirm BM involvement, IHC for CD4, CD56 and CD123 was performed on BM biopsies or clot sections. IHC revealed minimal BM involvement (CD123, 3/3; CD56, 2/3; CD4, 2/3) in three patients with BM that appeared morphologically normal. CONCLUSIONS: Our data clearly support the utility of IHC in diagnosing minimal BM involvement by BPDCN. Accordingly, we highly recommend immunohistochemical analyses for CD123, CD56 and CD4 in BPDCN patients, particularly in cases where the initial BM study indicates normal morphology.
Histopathology 12/2012; · 3.08 Impact Factor
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Tae-Dong Jeong, Chan-Jeoung Park,
Hyoeun Shim,
Seongsoo Jang,
Hyun-Sook Chi,
Dok Hyun Yoon,
Dae-Young Kim,
Jung-Hee Lee,
Je-Hwan Lee,
Cheolwon Suh,
Kyoo Hyung Lee
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ABSTRACT: Flow cytometric immunophenotyping has been used to identify neoplastic plasma cell populations in patients with multiple myeloma (MM). Previous reports have described the use of several antigens, including CD38, CD138, CD56, CD117, CD52, CD19 and CD45, to distinguish distinct populations of plasma cells. The aim of this study was to evaluate a simplified immunophenotyping panel for MM analysis.
A total of 70 patients were enrolled in the study, 62 of which were newly diagnosed with MM (untreated), whereas the remaining 8 were undergoing bone marrow assessment as part of follow-up after treatment (treated). Treated cases included 3 patients with relapse and 5 patients with persistence of MM. Multiparametric flow cytometric immunophenotyping was performed using monoclonal antibodies against CD56, CD19, CD138 (CD38), and CD45.
In differential counts, plasma cells in bone marrow (BM) accounted for 3.6-93.2% of the total nucleated cell count. The positive expression rates of CD56, CD19, CD138, and CD45 in neoplastic myeloma cells were 83.9%, 0%, 98.4%, and 37.1%, respectively, among the 62 untreated cases, and 75.0%, 0%, 87.5%, and 37.5%, respectively, among the 8 treated cases. CD19 expression of neoplastic plasma cells was negative in both untreated and treated cases.
The simplified immunophenotyping panel, CD56/CD19/CD138(CD38)/CD45, is useful for distinguishing neoplastic myeloma cells from reactive plasma cells in clinical practice. In addition, CD19 represents the most valuable antigen for identifying neoplastic myeloma cells in patients with MM.
The Korean journal of hematology 12/2012; 47(4):260-6.
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Annals of laboratory medicine. 11/2012; 32(6):452-4.
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ABSTRACT: Multiplex reverse transcription polymerase chain reaction (mRT-PCR) has recently emerged as an alternative to cytogenetics. We designed and used simplified mRT-PCR system as a molecular screen for acute leukemia. Fifteen fusion transcripts were included: BCR-ABL1, PML-RARA, ZBTB16-RARA, RUNX1-RUNX1T1, CBFB-MYH11, DEK-NUP214, TCF3-PBX1, ETV6-RUNX1, MLL-AFF1, MLL-MLLT4, MLL-MLLT3, MLL-MLLT10, MLL-ELL, MLL-MLLT1, and MLL-MLLT6. A total of 121 diagnostic acute leukemia specimens were studied, comparing the mRT-PCR system with standard cytogenetics. Fifty-six cases (46.3%) had fusion transcripts revealed by our mRT-PCR assay. The concordance rate between mRT-PCR and cytogenetics was 91.7%. However, false negative results were found in three cases who have inv(16), t(4;11) or t(11;19)(q23;p13.1), respectively. Seven cryptic translocations including ETV6-RUNX1, MLL-MLLT3, MLL-MLLT4, and PML-RARA were detected. This mRT-PCR assay is a useful screening tool in acute leukemia because it provides rapid and reliable detection of clinically important chimeric transcripts. In addition, cryptic translocations provide additional genetic information that could be clinically useful.
Journal of Korean medical science 10/2012; 27(10):1155-61. · 0.84 Impact Factor
