ALBERT

Description: Introduction: The assessment of thrombopoietic activity in bone marrow is necessary for patients with thrombocytopenia to achieve correct diagnoses and effective treatments. We evaluated the discriminatory power of the immature platelet fraction (IPF%) in differentiating hyperdestructive/consumptive thrombocytopenia from hypoproductive thrombocytopenia, and its potential use as a predictive marker for platelet recovery. Methods: Platelet indices including IPF% were measured in 105 healthy individuals (the control group), 31 patients with hyperdestructive/consumptive thrombocytopenia (14 with immune thrombocytopenic purpura [ITP] and 17 with liver cirrhosis), and 34 patients with hypoproductive thrombocytopenia (4 with aplastic anemia and 30 with cancer who were undergoing chemotherapy) by using a Sysmex XN-3000 hematology analyzer. Results: The platelet number in the hyperdestructive/consumptive thrombocytopenia group was significantly lower than that in the hypoproductive thrombocytopenia group (P

Description: Background: The use of laboratory reference intervals based on younger populations is of questionable validity in older populations. We established reference intervals for 16 complete blood count (CBC) parameters in healthy elderly Koreans aged ≥60 years and compared them to those of individuals aged 20-59 years. Methods: Among 64,532 individuals (39,609 men and 24,923 women) aged ≥20 years who underwent medical check-ups, 8,151 healthy subjects (12.6%, 5,270 men and 2,881 women, including 675 and 511, respectively, who were ≥60 years of age) were enrolled based on stringent criteria including laboratory, imaging, and endoscopy results; previous medical history; and medication history. CBC parameters were measured using an Advia2120i instrument. The difference between 2 age groups in subjects of each sex was compared using the Mann-Whitney U-test. P-values

Description: To evaluate the prognostic significance of the submicroscopic deletions of ABL or BCR gene associated with t(9;22) in CML, we investigated the incidence of ABL or BCR deletion on derivative chromosome 9 using fluorescent in situ hybridization (FISH), and analyzed the survival. FISH was performed using LSI BCR/ABL, dual fusion translocation probe on bone marrow cells of 86 patients with CML. Of 86 patients, ABL deletion was detected in 13 (15.1%) patients and BCR deletion in 8 patients (9.3%). Patients with ABL deletion showed shorter event-free survival time (EFS) than those without ABL deletion (P=0.020). Patients with BCR deletion showed significantly short overall survival time (OS) (P=0.039). Patients with ABL and/or BCR deletion (14/86 patients, 16.3%) showed significantly short OS and EFS (median OS: 43.0 months, median EFS: 40.0 months), compared to the patients without any deletions of BCR or ABL gene (median OS: 94.0 months, median EFS: 90.0 months)(P=0.041 for OS, P=0.008 for EFS). Patients with BCR deletion, all except one had a concomitant ABL deletion, suggesting that BCR deletion occurs in conjunction with ABL deletion. In patients with ABL deletion only, BCR/ABL rearrangement with b2a2 mRNA type tended to be more frequent than in patients without any deletion of the two genes (P=0.073). Deletion of any of BCR or ABL gene on derivative chromosome 9 was associated with both short OS and EFS. We conclude that deletion of not only ABL gene, but also BCR gene is a poor prognostic marker that indicates rapid disease progression in CML.

Description: Introduction: The prognosis of multiple myeloma (MM) depends on the underlying cytogenetic subtype. Recurrent cytogenetic changes including hyperdiploidy of odd-numbered chromosomes, -13/13q- and balanced translocations involving IGH have already been incorporated into risk stratification strategies and are used in standard clinical practice. Nevertheless, MM often exhibits a heterogenous and complex karyotype, and many other chromosomal abnormalities of uncertain clinical significance are observed. We performed a comprehensive analysis for the relationship between cytogenetic abnormalities of undetermined prognostic significance and known prognostic factors in MM. Materials and Methods: Conventional G-banding was performed in 333 newly diagnosed MM. Karyotypes were described using the most recent version of the International System for Human Cytogenetic Nomenclature. Translocations with breakpoints at p10, p11, q10, or q11 were all regarded as whole arm (centromere to centromere) translocations. Poor prognostic indicators as follows: hemoglobin (Hb) level 〈 10 g/dL, calcium level 〉 12 mg/dL, IgG level 〉 7 g/dL or IgA level 〉 5 g/dL, b2-microglobulin level 〉 5.5 mg/L, and albumin level 〈 3.5 g/dL. Creatinine level 〉 2 mg/dL, IgA type, lambda type, elevated free light chain level 〉 100 mg/dL, abnormal kappa/lambda ratio of 〉 4.0 or 〈 0.5, and elevated LDH level were also included. Results: Among the 333 MM patients, 212 showed a normal or good/intermediate karyotype (195 with normal karyotype; 17 with abnormal karyotype associated with good or intermediate prognosis); these served as the control group in this study. The remaining 121 had other cytogenetic abnormalities (with or without hyperdiploidy, or translocations associated with good or intermediate prognosis). Chromosomes 1p (12.0%), 1q (18.9%), 6q (7.2%), 8q (6.9%), 11q (5.4%), 12p (5.1%), 14q (9.3%) and 19q (5.1%).showed frequent abnormalities. Common breakpoints were p10–12, p13, p22 in 1p, q10–12, q21, q25, q32 in 1q; q21, q25 in 6q; q10, q22, q24 in 8q; q10, q13 in 11q; p10–12 in 12p; q24, q32in 14q and q10, q13.3 in 19q (Figure 1). Certain chromosomal abnormalities were associated with known prognostic factors (p-value 〈 0.05): 8q - IgA type; 1q - IgG level of 〉 5 g/dL or IgA level of〉 3 g/dL; 14q - kappa or lambda type chains 〉 100 mg/dL; 1p, 1q, 6q, and 19q - Hb 〈 10.0 g/dL; 1p and 12q - albumin 〈 3.5 g/dL; 14q and 19q –creatinine 〉 2.0 mg/dL; 1p, 1q, 6q, or 19q - b2-microglobulin 〉 5.5 mg/L; 1p, 8q, 11q, and 14q - calcium 〉 12 mg/dL; 1p, 3p, 12p, or 14q – elevated LDH level. Conclusion: We analyzed the distribution and clinical significance of the less commonly occurring cytogenetic abnormalities for the first time. Abnormalities in chromosomes 1p, 1q, 3p, 6q, 8q, 11q, 12q, 14q, and 19q were associated with clinical factors associated with a poor prognosis. Not all chromosomes showing frequent aberrations correlated with prognostic factors, indicating that it is not the presence of a cytogenetic abnormality in itself, but the particular chromosome(s) involved in the abnormality that is the key factor that determines the initial clinical characteristics of MM. Figure 1. Diagrammatic representation of the chromosomal breakpoints involved in structural abnormalities in multiple myeloma. Triangles represent breakpoints in interstitial or telomeric regions and diamonds represent breakpoints in centromeric or pericentromeric (p10-p11 or q10-q11) regions. Figure 1. Diagrammatic representation of the chromosomal breakpoints involved in structural abnormalities in multiple myeloma. Triangles represent breakpoints in interstitial or telomeric regions and diamonds represent breakpoints in centromeric or pericentromeric (p10-p11 or q10-q11) regions. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: A causal relationship between viral infection or decreased immunity and certain types of lymphoid malignancy has already been established. We performed a matched-control prospective follow-up study from a nationwide population-based dataset in South Korea to explore the association between herpes zoster exposure and the subsequent risk of lymphoid malignancies. Methods: Data in the Korean National Health Insurance Service-National Sample Cohort were collected from 2002 to 2013. We extracted the data of herpes zoster participants (n = 64,152) and their matched controls at a ratio of 1:4 (n = 1,061,539) and analyzed the occurrence of lymphoid neoplasms. Herpes zoster was diagnosed as ICD-10 B02, among them, we selected the participants who were treated for it ≥ 2 times or who were treated with antiviral medication ≥ 1 time. Lymphoid neoplasms were included using ICD-10 codes C81, C82, C83, C84, C85, C88, C90, and C91. For accurate participant inclusion, we used claim codes to select participants who were treated for lymphoid neoplasm ≥ 3 times or who were treated with chemotherapy or radiation therapy (n = 1,399). The matches were processed for age, group, sex, income group, region of residence, and past medical histories (hypertension, diabetes, and dyslipidemia). In both the herpes zoster and control groups, participants with a history of hematologic malignancy (lymphoid malignancy and acute leukemia) before the index date were excluded. In the herpes zoster group, 198 participants were excluded. The herpes zoster participants for whom we could not identify enough matching participants were excluded (n = 420). We excluded participants who were under 20 years old (n = 4,039). Finally, 1:4 matching resulted in the inclusion of 59,495 herpes zoster participants and 237,980 control participants. However, they were not matched for ischemic heart disease, cerebral stroke, or a history of depression as such strict matching increases participant drop out the due to lack of control participants. The income groups were initially divided into 41 classes (one health aid class, 20 self-employment health insurance classes, and 20 employment health insurance classes). These groups were recategorized into 11 classes (class 1 [lowest income] - 11 [highest income]). Region of residence was divided into 16 areas according to administrative district in South Korea. The past medical histories of participants were evaluated using ICD-10 codes. For accurate diagnosis, the presence of hypertension (I10 and I15), diabetes (E10-E14), and dyslipidemia (E78) was checked if the participants were treated ≥ 2 times. Ischemic heart disease (I24 and I25) and cerebral stroke (I60-I66) were assessed if the participants were treated ≥ 1 time. Depression was defined using the ICD-10 codes F31 (bipolar affective disorder) through F39 (unspecified mood disorder) diagnosed by a psychiatrist ≥ 2 times. Results: The rate of lymphoid neoplasm was higher in the herpes zoster group (0.15% [90/59,495]) than in the control group (0.08% [212/237,980], P 〈 0.001). The general characteristics (age, sex, income group, region of residence, and hypertension, diabetes, and dyslipidemia histories) of the participants were exactly the same due to the matching (P = 1.000). The rates of a history of ischemic heart disease and depression were higher in the herpes zoster group (each P 〈 0.05). The crude and adjusted HRs for lymphoid neoplasm were 1.70 (95% CI = 1.33 - 2.17) and 1.69 (95% CI = 1.32 - 2.16) in the herpes zoster group, respectively (each P 〈 0.001). In the subgroup analyses, the crude and adjusted HRs for lymphoid neoplasm were higher in all herpes zoster groups (each P 〈 0.05). The adjusted HRs were 1.72 (95% CI = 1.18 - 2.50) for those 〈 60 years old, 1.66 (95% CI = 1.20 - 2.31) for those ≥ 60 years old, 1.76 (95% CI = 1.24 - 2.48) for men, and 1.62 (95% CI = 1.14 - 2.31) for women. Conclusion: Our study demonstrates that herpes zoster infection increases the risk of subsequent lymphoid malignancies irrespective of age and gender in the Korean population. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 3874 Poster Board III-810 Introduction Myelomatous pleural effusion (MPE) in multiple myeloma (MM) is rare (

Description: Abstract 2661 Background. In lymphoma, bone marrow (BM) involvement is a sign of extensive disease and BM biopsy is a standard method in the evaluation of BM infiltration by disease. Because of patchy BM involvement pattern by lymphoma, the reported rates of unilateral involvement in bilateral biopsies range from 10% to 50%. However BM biopsy is an invasive and painful procedure. The value of unilateral versus bilateral BM biopsy remains controversial. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is a noninvasive imaging technique and currently it shows potential to detect BM involvement by lymphoma. Aims. We assess the abilities of FDG PET-CT to ascertain the presence of BM involvement in diffuse large B cell lymphoma (DLBCL) patients and to define the possibility that bilateral BM biopsies could be replaced by unilateral biopsy for DLBCL staging workup. Methods. We retrospectively reviewed medical records of histologically proven DLBCL patients from 2004 through 2010 at the Asan Medical Center and Hallym University Medical Center. All patients were examined by FDG PET-CT and bilateral BM biopsy at both posterior iliac crests for initial staging workup. Evaluation of PET studies was performed by board-certified nuclear medicine physicians of each institution. Quantitative analysis of FDG uptake was not performed. Data were expressed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for FDG PET-CT in evaluation of BM involvement by DLBCL, using BM biopsy as the reference standard. Two sets (right & left biopsy site) of pathologic and imaging data were analyzed separately. Results. Study population comprised 478 patients (median age 57, range 17–85 years; 269 male) with newly diagnosed DLBCL. Ann Arbor stage I, II, III and IV patients were 96, 120, 40 and 222, respectively. Overall, BM involvement by DLBCL that confirmed by bilateral BM biopsy occurred in 63 patients (13.2%, 15, 12, and 36 at right, left and both side biopsy, respectively). From the data of right side biopsy and FDG PET-CT images, comparison of the former and the later results revealed concordant positive findings in 22 cases (4.6%) and concordant negative findings in another 418 cases (87.4%). In 29 patients (6.1%) in whom FDG PET-CT returned findings of normal marrow, iliac crest BM biopsy revealed lymphomatous infiltration. On the other hand, in 9 patients (1.9%) in whom bilateral iliac crest BM biopsy had failed to reveal any abnormality, FDG PET-CT showed increased uptake. The calculated values for FDG PET-CT in evaluation of right BM infiltration were 43.1% (22/51) of sensitivity, 97.9% (418/427) of specificity, 71% (22/31) of PPV and 93.5% (418/447) of NPV. The values oriented from left BM biopsy and FDG PET-CT images were similar (sensitivity 41.7% (20/48), specificity 97.9% (421/430), PPV 69% (20/29), NPV 93.7% (421/449)). Conclusions. This study has the largest DLBCL cases among ever reported articles, and demonstrates not excellent sensitivity of FDG PET-CT against the results of BM biopsy for the detection of BM involvement in DLBCL patients. BM biopsy could not be completely replaced with FDG PET-CT. But it has relatively good PPV, FDG PET-CT will be a useful tool for image-guided biopsy for DLBCL staging. And in daily practice, clinicians could consider the possibility to do efficient unilateral BM biopsy for DLBCL patients who have increased posterior iliac crest FDG uptake, instead of bilateral biopsy. Disclosures: Kim: Novartis: Research Funding.

Description: Systemic capillary leak syndrome (SCLS) is a rare condition characterized by episodic capillary hyperpermeability. The manifestations of this syndrome are generalized edema, hypotension, hypoalbuminemia, hemoconcentration, renal shut-down and monoclonal gammopathy. The pathogenesis of SCLS is still unclear. The treatment of SCLS is empirical, including theophylline, terbutaline, steroids, loop diuretics, plasmapheresis and BMT. Some patients were diagnosed multiple myeloma during follow-up. Death during the acute attack from cardiopulmonary collapse or diuresis phase from pulmonary edema occurs in approximately one third of the cases. Therefore initial fluid therapy is one of critical care point, but there is no information what is the adequate volume expander during acute attack. We experienced two cases of SCLS with severe acute attack and showed rapid improvement of hypotension by 10% pentastarch. Case 1: A 36-year-old woman visited our hospital with systolic blood pressure (SBP) 50 mmHg, resting dyspnea, oliguria and anasarca. The laboratory findings showed Hb 19.2 g/dL, hematocrit (Hct) 53%, total protein / albumin 3.7 / 1.7 g/dL, BUN / creatinine 32.6 / 1.9 mg/dL and monoclonal IgG-kappa. There was no evidence of multiple myeloma. We diagnosed the patient as having SCLS and started intravenous infusionof 9 L of normal saline (NS), dexamethasone, aminophylline and inotropics for 8 hours. Despite massive fluid therapy, SBP was not increased, and respiratory failure due to pulmonary edema was developed. After infusion of 10% pentastarch 0.5 L every 8 hours, SBP was gradually increased to normal within 12 hours without NS infusion. From the next day, diuresis phase started, other clinical and laboratory findings became normal range. There was no long-term sequale, and no more attack for 1 year follow-up. Case 2: A 36-year-old woman was referred to our hospital with severe hypovolemic shock and anasarca. The laboratory findings showed typical SCLS with the presence of monoclonal IgG-kappa. There was no evidence of multiple myeloma. She had histories of similar several episodes for 3 years, was managed with infusion of albumin, NS and suffered from pulmonary edema. At this time, clinical and laboratory findings were severe: confusion, anuria, SBP 40 mmHg, Hb 21.1 g/dL, Hct 63%, BUN / creatinine 22.6 / 2.8 mg/dL, total protein / albumin 4.4 / 2.5 g/dL. Two hours after using 0.5 L of 10% pentastarch and 2 L of NS, SBP and urine output increased to 127 mmHg and 50 ml/hour, respectively. Other clinical and laboratory findings restored and diuresis phase started within 1 day and there was no pulmonary edema. Acute management during hypotensive attack is very important to reduce mortality of SCLS. Because shift of fluid and protein by capillary hyperpermeability is the pathophysiology of this syndrome, total body fluid is not decreased. Thus massive crystalloid fluid, albumin infusion would not effective during hypotensive phase of SCLS and exacerbate edema. Hypoalbuminemia (molecular weight (MW) 69,000 dalton) is very common manifestation of SCLS, and Atkinson et al (Medicine1997; 56;225–39) reported that egress from vascular compartment was limited to proteins of MW up to 200,000 dalton. Under this knowledge, we used pentastarch (MW 240,000 dalton) during acute SCLS attacks and it showed dramatic responses. Pentastarch would be a very effective treatment for acute attack and might decrease acute mortality of SCLS.

Description: Tissue factor (TF) is the primary initiator of coagulation, and the TF pathway mediates signaling through protease-activated receptors (PARs). In sepsis, TF is up-regulated as part of the proinflammatory response in lipopolysaccharide (LPS)–stimulated monocytes leading to systemic coagulation activation. Here we demonstrate that TF cytoplasmic domain–deleted (TFΔCT) mice show enhanced and prolonged systemic coagulation activation relative to wild-type upon LPS challenge. However, TFΔCT mice resolve inflammation earlier and are protected from lethality independent of changes in coagulation. Macrophages from LPS-challenged TFΔCT mice or LPS-stimulated, in vitro–differentiated bone marrow–derived macrophages show increased TF mRNA and functional activity relative to wild-type, identifying up-regulation of macrophage TF expression as a possible cause for the increase in coagulation of TFΔCT mice. Increased TF expression of TFΔCT macrophages does not require PAR2 and is specific for toll-like receptor, but not interferon γ receptor, signaling. The presence of the TF cytoplasmic domain suppresses ERK1/2 phosphorylation that is reversed by p38 inhibition leading to enhanced TF expression specifically in wild-type but not TFΔCT mice. The present study demonstrates a new role of the TF cytoplasmic domain in an autoregulatory pathway that controls LPS-induced TF expression in macrophages and procoagulant responses in endotoxemia.