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Purpose@#Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions. @*Materials and Methods@#Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients. @*Results@#We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients. @*Conclusion@#Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.
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Purpose@#The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC. @*Materials and Methods@#Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed. @*Results@#PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035). @*Conclusion@#Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.
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Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and an increase in MVD can be used as a marker of poor prognosis in MM patients. We developed an automated image analyzer to assess MVD from images of BM biopsies stained with anti-CD34 antibodies using two color models. MVD was calculated by merging images from the red and hue channels after eliminating non-microvessels. The analyzer results were compared with those obtained by two experienced hematopathologists in a blinded manner using the 84 BM samples of MM patients. Manual assessment of the MVD by two hematopathologists yielded mean±SD values of 19.4±11.8 and 20.0±11.8. The analyzer generated a mean±SD of 19.5±11.2. The intraclass correlation coefficient (ICC) and Bland-Altman plot of the MVD results demonstrated very good agreement between the automated image analyzer and both hematopathologists (ICC=0.893 [0.840–0.929] and ICC=0.906 [0.859–0.938]). This automated analyzer can provide time- and labor-saving benefits with more objective results in hematology laboratories.
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Objective@#We investigated the proportions of and reclassified BRCA1/2 variants of unknown significance (VUS) in Korean patients with epithelial ovarian, tubal, and primary peritoneal cancers. @*Methods@#Data from 805 patients who underwent genetic testing for BRCA1/2 from January 1, 2006 to August 31, 2018 were included. The VUS in BRCA1/2 were reclassified using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines. @*Results@#A BRCA1 pathogenic variant was found in 17.0% (137/805) of the patients, and BRCA1 VUS were found in 15.9% (128/805) of the patients. Further, 8.7% (69/805) of the patients possessed a BRCA2 pathogenic variant and 18.4% (148/805) of the patients possessed BRCA2 VUS. Fifty-three specific BRCA1 VUS were found and 20 were further reclassified as benign (n=11), likely benign (n=5), likely pathogenic (n=3), and pathogenic (n=1). The remaining 33 remained classified as VUS. For BRCA2, 55 specific VUS were detected; among these, 14 were reclassified as benign or likely benign, and 2 were reclassified as likely pathogenic. Among the 805 patients, 195 were found to have only VUS and no pathogenic variants (PV), and 41.5% (81/195) were reclassified as benign or likely benign, and 10.3% (20/195) as pathogenic or likely pathogenic variants. @*Conclusions@#Approximately 33.3% (36/108) of the specific BRCA1/2 variants analyzed in this study that were initially classified as VUS over a 13-year period were reclassified. Among these, 5.6% (6/108) were reclassified as pathogenic or likely pathogenic variants.
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Background@#Clinical specimens are valuable materials that require a traceable management system. Maintenance of temperature and loss prevention during transport are important for the reliability of the clinical test results. Current transportation systems can suffer from temperature changes and agitation. Quality improvement in this pre-analytic phase is required. This study acquired preliminary data from a newly developed specimen transportation system adopting a real-time temperature monitoring during transportation using temperature sensor and global positioning system to establish appropriate guidelines. @*Methods@#Temperature preservation performance was compared between two transportation boxes (newly developed one [A] and conventional one [B]) at exterior temperatures of 35℃ and ?18℃, reflecting the extreme temperature range in Korea. Influences of the temperatures on analytical results of whole blood, serum, plasma, and urine specimens were investigated, as were the effects of vibration. @*Results@#The interior temperature of box A measured at multiple sites was maintained within 1.0?9.0℃ at both exterior temperatures. The interior temperature of box B was outside of this range. The analyzed parameters varied comparably with the variations occurring at the recommended and published storage temperature. Vibration affected nonspecific enolase and lactate dehydrogenase. @*Conclusions@#Temperature preservation and real-time monitoring during specimen transportation are important. The present data highlight the importance of transportation conditions and indicate that laboratories should know the characteristics of temperature changes in their transportation system.
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Objective@#We investigated the proportions of and reclassified BRCA1/2 variants of unknown significance (VUS) in Korean patients with epithelial ovarian, tubal, and primary peritoneal cancers. @*Methods@#Data from 805 patients who underwent genetic testing for BRCA1/2 from January 1, 2006 to August 31, 2018 were included. The VUS in BRCA1/2 were reclassified using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines. @*Results@#A BRCA1 pathogenic variant was found in 17.0% (137/805) of the patients, and BRCA1 VUS were found in 15.9% (128/805) of the patients. Further, 8.7% (69/805) of the patients possessed a BRCA2 pathogenic variant and 18.4% (148/805) of the patients possessed BRCA2 VUS. Fifty-three specific BRCA1 VUS were found and 20 were further reclassified as benign (n=11), likely benign (n=5), likely pathogenic (n=3), and pathogenic (n=1). The remaining 33 remained classified as VUS. For BRCA2, 55 specific VUS were detected; among these, 14 were reclassified as benign or likely benign, and 2 were reclassified as likely pathogenic. Among the 805 patients, 195 were found to have only VUS and no pathogenic variants (PV), and 41.5% (81/195) were reclassified as benign or likely benign, and 10.3% (20/195) as pathogenic or likely pathogenic variants. @*Conclusions@#Approximately 33.3% (36/108) of the specific BRCA1/2 variants analyzed in this study that were initially classified as VUS over a 13-year period were reclassified. Among these, 5.6% (6/108) were reclassified as pathogenic or likely pathogenic variants.
ABSTRACT
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.
Subject(s)
Humans , Bone Marrow , Diagnosis , Flow Cytometry , Hyperplasia , Medical Records , Megakaryocytes , Paraneoplastic Syndromes , Paraproteinemias , Plasma Cells , POEMS Syndrome , Polyneuropathies , SkinABSTRACT
Assessment of bone marrow (BM) involvement in peripheral T-cell lymphoma, not otherwise specified (PTCL) is straightforward in cases of extensive involvement but difficult in cases of minimal to partial involvement. We evaluated the usefulness of CD3 as an immunohistochemical marker for assessing BM involvement in PTCL patients. BM biopsies of 92 PTCL patients were immunohistochemically stained for CD3, CD4, CD8, CD20, and CD56, and evaluated by two hematopathologists. CD3 positivity was graded according to the proportion of CD3-positive cells and the number of CD3-positive cells in a cluster. These criteria were used to determine the cut-offs at which significant differences in progression-free survival (PFS) and overall survival (OS) were observed. Multivariate analysis controlling the International Prognostic Index (IPI) score and its individual factors revealed that >20 CD3-positive cells in a cluster adversely affected PFS (relative risk [RR], 2.1; 95% confidence interval [CI], 1.0–4.3; P=0.047) and OS (RR, 2.4; 95% CI, 1.1–5.1; P=0.028) independent of IPI score. A cluster with >20 CD3-positive cells is a candidate indicator for BM involvement in PTCL.
Subject(s)
Humans , Biopsy , Bone Marrow , Disease-Free Survival , Lymphoma, T-Cell, Peripheral , Multivariate AnalysisABSTRACT
BACKGROUND: Coronary artery disease is an important cause of death in adults and stent insertion is one of the treatment modalities. The most severe adverse effect of a stent insertion is the formation of a thrombus; therefore, antiplatelet agents are used. The addition of cilostazol to low-dose aspirin and clopidogrel results in a better antiplatelet effect. However, laboratory tests to monitor the effect of cilostazol are insufficient. METHODS: We tested the inhibitory effect of cilostazol using maximal platelet aggregation in 20 healthy volunteers. Conditions for incubation and concentrations of cilostazol and prostaglandin E1 (PGE1) were established and aggregation was induced by 5'-adenosine diphosphate (ADP) and measured with light transmission aggregometry (LTA). Blood samples were incubated with 1 µM and 2 µM cilostazol for 10 minutes at room temperature, and 80 nM PGE1 was added and incubated for an additional 10 minutes. Aggregation was induced by ADP and reactivity was evaluated. RESULTS: The average maximum aggregation (MA) was 58.1% at 1 µM cilostazol and 22.0% when PGE1 was added. The average MA was 42.8% when cilostazol concentration was increased to 2 µM and 21.2% when PGE1 was added. Average inhibition of aggregation at 1 µM cilostazol was not statistically significant (P=0.085), but was significant (P=0.004) at 2 µM cilostazol. Aggregation was not inhibited even with 2 µM cilostazol and PGE1 in 2 volunteers, which suggests possible resistance to cilostazol. CONCLUSIONS: We designed a method to monitor the effect of cilostazol using in vitro incubation with PGE1.
Subject(s)
Adult , Humans , Adenosine Diphosphate , Alprostadil , Aspirin , Cause of Death , Coronary Artery Disease , Healthy Volunteers , In Vitro Techniques , Methods , Platelet Aggregation , Platelet Aggregation Inhibitors , Stents , Thrombosis , VolunteersABSTRACT
Paroxysmal cold hemoglobinuria (PCH) is a rare diagnosis of acquired hemolytic anemia in children, which is caused by a specific cold antibody named Donath-Landsteiner hemolysin. Although various bacteria or viruses were reported as triggering factor of PCH, childhood PCH related to Chlamydia pneumoniae infection is uncommon. The authors report a case of childhood PCH which is related with suspicious Chlamydia pneumoniae infection, with a review of pertinent literature.
Subject(s)
Child , Humans , Anemia, Hemolytic , Bacteria , Chlamydia Infections , Chlamydophila pneumoniae , Diagnosis , Hemoglobinuria, ParoxysmalABSTRACT
No abstract available.
Subject(s)
Female , Humans , Middle Aged , Base Sequence , Benzamides/therapeutic use , Bone Marrow/pathology , Fusion Proteins, bcr-abl/genetics , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Philadelphia Chromosome , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Sequence Analysis, DNA , Thiazoles/therapeutic use , Translocation, GeneticABSTRACT
Paroxysmal cold hemoglobinuria (PCH) is a rare diagnosis of acquired hemolytic anemia in children, which is caused by a specific cold antibody named Donath-Landsteiner hemolysin. Although various bacteria or viruses were reported as triggering factor of PCH, childhood PCH related to Chlamydia pneumoniae infection is uncommon. The authors report a case of childhood PCH which is related with suspicious Chlamydia pneumoniae infection, with a review of pertinent literature.
Subject(s)
Child , Humans , Anemia, Hemolytic , Bacteria , Chlamydia Infections , Chlamydophila pneumoniae , Diagnosis , Hemoglobinuria, ParoxysmalABSTRACT
BACKGROUND: Clinical and Laboratory Standards Institute (CLSI) guidelines (H42-A2) recommend the "CD45/SSC" gating method for assays on lymphocyte subset enumeration and CD16 exclusion for assays enumerating NK cells. In contrast, the Flow Cytometry Checklist (06/17/2010) of the College of American Pathology does not recommend a specific lymphocyte gating method, but recommends the correction of lymphocyte subset results for lymphocyte gate purity. METHODS: We compared lymphocyte subset results of EDTA-treated blood from 102 patients with various diseases and 12 normal controls, using 3 lymphocyte gating methods (CD45/SSC, FSC/SSC, and lymphocyte gate purity correction after FSC/SSC gating), and assessed the proportion of CD56-/CD16+ NK cells within the total NK cell population. RESULTS: Lymphocyte gate purity increased as the percentage of lymphocytes increased. However, lymphocyte subsets that consistently showed high lymphocyte gate purity could not be identified. The purity of the T cell population differed significantly depending on the gating method used: CD45/SSC vs. FSC/SSC, P=0.027; CD45/SSC vs. gate purity correction after FSC/SSC, P=0.002. However, the lymphocyte gate purity correction after FSC/SSC gating did not significantly improve the accuracy of the lymphocyte subset enumeration assay using FSC/SSC gating. The subset of CD56-CD16+ NK cells, constituted an average of 17.1% of total NK cells. Patients had higher proportions of CD56-CD16+ NK cells (13.1-25.5%) than did the normal controls (9.52%). CONCLUSIONS: In flow cytometric assays to evaluate lymphocytic subsets, the CD45 is inevitable for lymphocyte gating, whereas the measurement of CD16 is essential for the evaluation of NK cell proportions.
Subject(s)
Humans , Checklist , Flow Cytometry , Killer Cells, Natural , Lymphocyte Subsets , LymphocytesABSTRACT
BACKGROUND: It is critical to differentiate heparin-induced thrombocytopenia (HIT) from disseminated intravascular coagulation (DIC) in heparinized intensive care unit (ICU) patients with thrombocytopenia because the therapeutic approach differs based on the cause. We investigated the usefulness of PF4/heparin antibody tests in these patients. METHODS: A total of 127 heparinized ICU patients whose platelet counts were 50% after 5-10 days of heparin therapy were enrolled. PF4/heparin antibodies were measured using 2 immunoassays. We assessed the probability of HIT by using Warkentin's 4T's scoring system for antibody positive patients and compared routinely performed coagulation test results between patients with and without antibodies to evaluate the ability of these tests to discriminate between HIT and DIC. RESULTS: Positive results were obtained for 14 (11.0%) and 11 (8.7%) patients in the 2 assays. The analysis performed using the 4T's scoring system revealed that 11 of 20 (15.7%) patients with antibodies in at least 1 assay had intermediate or greater probability of HIT. Patients without antibodies had significantly higher levels of D-dimer than those with antibodies. However, there were no intergroup differences in platelet counts, PT, aPTT, fibrinogen, DIC score, and rate of overt DIC. CONCLUSION: Seropositivity for PF4/heparin antibody was 8.7-11.0% in the patients with thrombocytopenia, and more than a half of them had an increased probability of HIT. Among the routine coagulation tests, only D-dimer was informative for differentiating HIT from DIC. PF4/heparin antibody test is useful to ensure appropriate treatment for thrombocytopenic heparinized ICU patients.
Subject(s)
Humans , Antibodies , Dacarbazine , Dietary Sucrose , Disseminated Intravascular Coagulation , Fibrin Fibrinogen Degradation Products , Fibrinogen , Heparin , Immunoassay , Critical Care , Intensive Care Units , Platelet Count , Platelet Factor 4 , ThrombocytopeniaABSTRACT
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Humans , Antibodies, Monoclonal , Bone Marrow , Cell Count , Flow Cytometry , Follow-Up Studies , Immunophenotyping , Multiple Myeloma , Plasma , Plasma Cells , RecurrenceABSTRACT
BACKGROUND: Proper gating is important in flow cytometric assays of lymphocyte subsets. Forward light scatter (FSC)/side light scatter (SSC) gating requires application of a lymphocyte purity correction when lymphocyte purity is less than 95%. We compared 3 different gating methods to establish an accurate gating method appropriate for a T-lymphocyte subset assay of bronchoalveolar lavage (BAL) fluid. METHODS: Leukocyte numbers and subtypes in 31 BAL fluid samples were assessed manually and by using an automatic hematology analyzer. T-lymphocyte subsets (T cells, T helper/inducer cells [Th], and T suppressor/cytotoxic cells [Tc]) were assessed by flow cytometry. We compared 3 methods of lymphocyte gating: CD45/SSC gating (reference method), FSC/SSC gating, and FSC/SSC gating with application of a lymphocyte purity correction. Lymphocyte purity was determined by CD45/CD14 staining of BAL fluid. RESULTS: We observed a significant correlation between lymphocyte percentage and lymphocyte purity (r = 0.453, P = 0.011). T-cell results obtained using the reference method were not correlated with the results of the other 2 gating methods (r = 0.189 each, P = 0.308 for FSC/SSC gating and P = 0.310 for FSC/SSC gating with purity correction). Mean differences between the reference method and FSC/SSC gating (T cells: 14.4%, P = 0.002; Th cells: 7.7%, P = 0.006; Tc cells: 7.1%, P = 0.001) were greater than those between the reference method and FSC/SSC gating with purity correction (T cells: 12.1%, P = 0.004; Th cells: 1.7%, P = 0.608; Tc cells: 0.2%, P = 0.957). CONCLUSIONS: Lymphocyte purity correction after FSC/SSC gating improved the accuracy of Th- and Tc-cell measurements, but not T-cell measurements. CD45 is essential for lymphocyte gating in T-lymphocyte subset assays of BAL fluid.
Subject(s)
Bronchoalveolar Lavage , Bronchoalveolar Lavage Fluid , Flow Cytometry , Hematology , Leukocyte Count , Light , Lymphocyte Subsets , Lymphocytes , T-Lymphocyte Subsets , T-LymphocytesABSTRACT
BACKGROUND: Continuous monitoring systems have allowed determination of the time-to-positivity (TTP). We evaluated the clinical relevance of TTP in the BACTEC9240 system (Becton-Dickinson, USA). METHODS: A total of 2,354 vials of positive blood cultures were evaluated over 2 months. TTP was monitored from each of BACTEC Plus Aerobic/F (BD) or Pediatric Plus/F and Lytic Anaerobic/F bottles, and the differential time-to-positivity (DTP) for blood samples drawn simultaneously via catheter and a peripheral site was determined. RESULTS: The average TTP of the positive vials was 17.4 hr, and 79.9% and 95.2% of the vials showed positivity within 24 and 48 hr, respectively. While the average TTP values for Aeromonas hydrophila, Bacillus cereus, Acinetobacter baumannii, and Streptococcus pneumoniae were less than 10 hr, those for Candida spp., anaerobes, Propionibacterium acnes, Corynebacterium spp, Bacillus spp. other than cereus, and coagulase-negative staphylococci were 35.3, 27.0, 56.8, 45.8, 23.0, and 26.3 hr, respectively. The negative predictive values of TTP over 24 hr to predict Staphylococcus aureus among staphylococci and S. pneumoniae among alpha-hemolytic streptococci were 76.7% and 100%, respectively. Enterobacteriaceae and Enterococcus faecalis showed shorter TTP in anaerobic vials than in aerobic vials. DTP of more than 2 hr was observed for 27.8%, 72.2%, and 45.5% of S. aureus, S. epidermidis, and Candida spp. CONCLUSIONS: TTP can be used to discriminate pathogens and contaminants. The shorter TTP in anaerobic vials of certain Enterobacteriaceae and Enterococcus spp. would facilitate further identification. DTP is useful for diagnosing catheter-related bloodstream infection by S. aureus, S. epidermidis, and Candida spp.
Subject(s)
Humans , Bacteremia/diagnosis , Bacteria, Aerobic , Bacteria, Anaerobic , Bacteriological Techniques/instrumentation , Reagent Kits, Diagnostic , Time FactorsABSTRACT
BACKGROUND: Therapy-related myeloid neoplasm (t-MN) is a distinct class of acute myeloid leukemia (AML) in the World Health Organization (WHO) classification. Both AML and acute lymphoblastic leukemia (ALL) may develop after treatment for primary cancer. Topoisomerase inhibitors are commonly used to treat breast cancer patients and are well-known for their effect on leukemogenesis of therapy-related acute leukemias (t-AL). METHODS: We retrospectively evaluated bone marrow test results, chromosomal findings, and clinical characteristics of 12 patients who received topoisomerase inhibitors for breast cancer treatment and later developed acute leukemia. RESULTS: Fourteen patients (0.2%) developed t-AL after treatment for breast cancer. Topoisomerase inhibitors were administered to 12 patients. Among them, 9 patients (75%, 9/12) were diagnosed with therapy-related AML (t-AML) and 3 patients (25%, 3/12) with therapy-related ALL (t-ALL). Eight patients (67%, 8/12) showed translocation involving 11q23 and 3 different partner genes, 19p13.1 (37.5%, 3/8), 9p22 (37.5%, 3/8), and 4q21 (25%, 2/8). The median interval between completion of chemotherapy for breast cancer and occurrence of t-AL was 25 months. Patients with 11q23 translocation showed markedly poorer event-free survival than the group without involvement of 11q23. CONCLUSION: The incidence rate of t-AL after treatment for breast cancer was 0.2% in a tertiary hospital in Korea. Translocation involving the MLL gene was frequently found in t-AL caused by a topoisomerase inhibitor and was related to poor prognosis.
Subject(s)
Humans , Bone Marrow , Breast , Breast Neoplasms , Disease-Free Survival , Incidence , Korea , Leukemia , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Retrospective Studies , Tertiary Care Centers , Topoisomerase Inhibitors , World Health OrganizationABSTRACT
Anti-Ok(a) was detected in a 56-year-old female patient who was admitted for surgical treatment of degenerative scoliosis. Because Oka is a high-incidence antigen, anti-Ok(a) antibody is extremely rare. No case of hemolytic transfusion reaction or hemolytic disease of the fetus and newborn caused by anti-Ok(a) antibody has been reported so far, however, it is likely that anti-Ok(a) is clinically significant based on several in vivo and in vitro studies. When a patient who is bearing anti-Ok(a) needs transfusion of RBCs, transfusion of autologous blood or Ok(a-) RBCs from family members is recommended.