bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALDH1 Expression in Diffuse Large B-Cell Lymphoma: A Study of 88 Cases.
Authors: Olson Ryan K. , Li Li , Sheehan C. E , Homan Suzanne M. , Hayner-Buchan Alida , Nazeer Tipu 
Published: October 2019

Abstract
Abstract 5019

Introduction
Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous category and tremendous effort has been made to identify sub-groups that are prognostically significant and to guide therapeutic decisions. Aldehyde dehydrogenase (ALDH) a family of ubiquitous enzymes throughout mammalian tissues catalyzes the oxidation of aldehydes to their corresponding carboxylic acids. Isoform 1 (ALDH1) plays a role in the biosynthesis of retinoic acid from Vitamin A. Retinoic acid is a regulator of cellular proliferation, differentiation and survival in normal human tissues. High expression of ALDH1 has been demonstrated in the putative cancer stem cells in malignancies of breast, lung, colon and other organs. Its expression has been associated with increased replicative potential, the ability to differentiate along multiple development lines, high tumorigenic potential and increased metastatic potential. However, more recently ALDH1 expression has been shown to correlate with favorable outcome in ovarian cancer. It has not been studied in DLBCL. The aim of the current study is to evaluate the expression of ALDH1 in DLBCL.

Methods & Materials
Formalin-fixed, paraffin embedded sections from 88 DLBCLs, were immunostained by automated methods (Ventana Medical Systems, Inc, Tucson, AZ) using monoclonal mouse anti-human ALDH antibody (Clone: 44/ALDH; Immunogen: Human ALDH1, aa 7 – 128; BD Transduction Laboratories). Cytoplasmic immunoreactivity was semi quantitatively assessed in all cases. Scoring was based on staining intensity (weak, moderate, intense) and percentage of positive cells (focal <= 25%, regional 26-50%, diffuse >50%).

Results
were correlated with clinicopathologic variables.

Results
High expression of ALDH1 was observed in 26/88 (30%) cases of DLBCL. The staining intensity and distribution pattern varied somewhat by outcome data. Remission status was known in 23 patients. 18 patients achieved complete remission. Interestingly, all 7 patients with high expression of ALDH1 achieved complete remission (p= 0.095). Recurrence information was known in 87 patients. High expression of ALDH1 was seen in 26 cases. Only one of these patients recurred (p=0.19). No association was seen with stage, HIV status, survival or age.

Conclusion
We have demonstrated that ALDH1 is expressed in DLBCL. Moreover, cases with high expression of ALDH1 trend towards complete remission and lack of recurrence. Further studies of ALDH1 expression in DLBCL appear warranted, potentially defining prognostically relevant sub-groups.

Disclosures
No relevant conflicts of interest to declare.
Primary Cutaneous Follicle Center Lymphoma in An HTLV-1 Carrier.
Authors: Phillips Adrienne A. , Oshikanlu Zion , Nuovo Gerard J , Bhagat Govind , Savage David 
Published: October 2019

Abstract
Abstract 5032

Background
Human T-lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus associated with adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm of mature CD4+ T-lymphocytes which always shows monoclonal integration of HTLV-1 provirus DNA. HTLV is not associated with B-cell non-Hodgkin's lymphoma (B-NHL); however rare cases of B-NHL have been reported in HTLV-1 carriers, leading some to hypothesize a role for HTLV-1 in B-cell lymphogenesis. We report a case of a Jamaican male HTLV-1 carrier with primary cutaneous follicle center lymphoma of B-cell origin and explore the link between HTLV-1 and B-NHL.

Case Report
A 55 year old Jamaican male was seen in our hematology clinic for evaluation of multiple scalp masses progressive over six months. The lesions were painful, pruritic, but not associated with other constitutional symptoms. He had been in good health prior to the onset of these symptoms, and denied toxic habits or exposures. Physical examination revealed multiple firm, non-tender scalp masses, the largest measuring 3.0 × 2.0 cm; the overlying skin was nodular and erythematous but without breakdown or discharge. His complete blood count, basic metabolic profile, hepatic function and lactate dehydrogenase were all within normal limits. On excisional biopsy, the dermis showed a dense lymphoid infiltrate of medium to large sized cells, with a nodular and trabecular pattern of growth from the superficial dermis to the aponeurosis. Numerous large centroblast-like cells were present. Immunohistochemical stains demonstrated the following phenotype: CD45+, CD20+, CD79a+, BCL2+/-, BCL6+/-, CD10+, and MUM-/+. A stain for CD21 highlighted compact and fused/contiguous follicular dendritic cell meshworks in association with the neoplastic B-cell infiltrate. Staining with Ki-67 highlighted a variable but high proliferation rate (80%). A moderate infiltrate of small-sized T-cells (CD3+, CD5+) was also present. These features were diagnostic of a primary cutaneous follicle center lymphoma. Evaluation with the MYC breakapart probe showed no evidence of rearrangement; RT in-situ PCR for HTLV-1 showed a signal in many of the infiltrating T-cells. He was seropositive for positive HTLV-1 and negative for HIV and EBV infection. Bone marrow biopsy and aspiration and additional staging CTs were unremarkable. The patient received 4 cycles of R-CHOP chemotherapy and has been in a complete remission for 2 years.

Discussion
We report a case of a Jamaican male HTLV-1 carrier with cutaneous lymphoma of B-cell origin with detection of HTLV-1 proviral DNA in the neoplastic cells by RT in-situ PCR. Our findings lead us to speculate that HTLV-1 infected T-cells and/or an immunodeficient state in certain HTLV-1 carriers might allow for the development of B-cell lymphoma. Further research on the pathogenesis of HTLV-1 in B cell lymphomagenesis needs to be explored.

Disclosures
No relevant conflicts of interest to declare.
Venous Thromboembolism in the Elderly: Epidemiological Data Overview Based On the 2149-Patients Prospective OPTIMEV Cohort.
Authors: Pernod Gilles , Labarere Jose , Sevestre Marie Antoinette , Bosson Jean Luc 
Published: October 2019

Abstract
Abstract 5063
VTE is a multifactorial disease, but one of the strongest risk factor is age. Despite this high incidence, there is surprisingly little known about VTE in this population. So, based on the large OPTIMEV cohort study on VTE, the aim of this study was to focus on epidemiological information regarding VTE among old population.
OPTIMEV was a multicentre prospective cohort study of patients referred for clinically suspected VTE throughout France. VTE presentations were categorized using objective tests including ultrasonography, lung scan and helical CT scan. Subjects without a confirmed diagnosis of VTE were used as controls.
A total of 8256 patients were included in the OPTIMEV study, among which the aged study population (> 75y) was 2149. The median age of the old group was 81 years (76 - 101 years). Among this cohort, a total of 655 patients (30.5%) were positive cases of VTE, including 203 isolated distal DVT (31%), and 452 (69%) proximal DVT +/- PE. Diagnosis of VTE was ruled out in 1494 patients (69.5%). To identify potential specific risk factors in older patients, we compared VTE positive aged patients to younger. For this purpose, we tested by logistic regression the interaction between age (more or less than 75) and risk factors. Personal or familial history of VTE, travel, cardiac or respiratory insufficiency were not specific of the difference in incidence of VTE in older compared to younger patients. Only male gender (OR 1.4, 95% CI 1.1 – 1.9), bed rest (OR 1.4, 95% CI 1.1 – 1.9), lower limb immobilization (OR 1.1, 95% CI 0.5 – 2.5 and surgery <45d (OR 1.2, 95% CI 0.9 – 1.7) were found to be significantly different risk factors for VTE according to age.
Our epidemiological data, based on a large cohort, showed few really specific risk factors in this old population, compared to younger.

Disclosures
No relevant conflicts of interest to declare.
Transient Iron Resistance in Severe Iron Deficiency Anemia.
Authors: Milani Cannon , Colvin Gerald A. , Mazur Eric , Berz David 
Published: October 2019

Abstract
Abstract 5104

Background
Iron deficiency is the primary cause of anemia in the United States. Occasionally the anemia is severe enough to require transfusion of blood products. Anecdotal case reports described a state of transient iron intolerance in patients with profound, prolonged iron deficiency. We are presenting a study, evaluating in a prospective fashion how the iron parameters of patients with severe iron deficiency respond to blood transfusion and compare this to the trajectory of patients with other causes of anemia.

Methods
We included nineteen consecutive patients admitted to the medical floors with the diagnosis of anemia. Six of them had severe iron deficiency. The remaining part of the cohort carried the diagnosis of refractory anemia or anemia of chronic disease. We evaluated serum iron level, total iron binding capacity (TIBC), transferrin, and ferritin levels immediately prior to the transfusion of two units PRBCs and then six, twelve, twenty four, and forty eight hours after the completion of the transfusion, and correlated them to the pre- and post-transfusional IL-1, IL-2, IL-6, IL-10, IL-18, MIB-1β, MCP-1, erythropoietin, and hepcidin values of severely iron deficient patients and patients with other causes of their anemia.

Results
Patients with severe iron deficiency anemia showed a transient peak of the serum iron levels immediately after completion of blood transfusion. This normalized after 24 hours. In the not severely iron deficient population, no peak in the serum iron levels was observed. The remaining iron parameters, namely TIBC, transferrin, and ferritin remained unchanged. The transient elevation of the serum iron levels correlated with changes in the level of different cytokines.

Conclusion
Severely iron deficient patients show a transient intolerance to externally, parenterally delivered iron, that normalizes within 24 hours.

Disclosures
No relevant conflicts of interest to declare.
Efficacy of Ursodeoxycholic Acid with Low-Dose Heparin and Prostaglandin E1 in the Prevention of Hepatic Veno-Occlusive Disease After Allogenic Hematopoietic Stem Cell Transplantation in Children with β-Thalassemia Major.
Authors: Wu Xuedong , Liu Huaying , He Yuelin , Feng Xiaoqin , Chen Geyu , Su Qingxia , Meng Fanyi , Li Chunfu 
Published: October 2019

Abstract
Abstract 5109

Objective
This study was to explore more efficient methods of prevention of VOD in patients with thalassemia. We explore the efficacy of VOD prophylaxis with ursodeoxycholic acid, lipo-prostaglandin E1 and low-dose unfractionated heparin in allogeneic heamatopoietic stem cell transplantation(HSCT) for patients with thalassemia. Methods:Fifty-eight children with β-thalassemia major received allo-SCT for 61 times. For the prevention of VOD, all patients received low-dose heparin(100-150IU/kg · d) and also received PGE1(1-1.5 · d) by continuous intravenous infusion from the beginning of conditioning treatment to the 20th day after allo-SCT. Patients who received ursodeoxycholic acid (12mg/kg.d,oral,from the beginning of conditioning treatment to the 90th day after allo-SCT)were used as the study group (n=33).Patients who did not received ursodeoxycholic acid were used as the control group (n=28).Results:VOD occurred in 3 patients(8.8%) in the study group. Ten patients in the control group had VOD(37.0%).There were no obvious drug adverse effects in the two groups.

Conclusions
Ursodeoxycholic acid with low-dose heparin and PGE1(study group) is more effective than low-dose heparin and PGE1 only (control group) for the prevention of VOD after allo-SCT for children with β-thalassemia major.

Disclosures
No relevant conflicts of interest to declare.
The Preparative Method and Clinical Application of Autologous memory T Lymphocyte.
Authors: LI D. , Ouyang Jian , LI CP , Chen Jh , Zhou M. , Zhou Rong-Fu 
Published: October 2019

Abstract
Abstract 5123

Background
The term autolymphocyte therapy refers to an adoptive cellular transfer strategy based on the ex vivo activation of memory T cells. The assumption is that because patients with metastatic cancer have been previously exposed to tumor antigens, memory T cells exist which can be collected and activated ex vivo. The result in autologous cytokines that can be used to activate other T cells. The method is simpler than it sounds and basically consisted of 2 cell collections using a cell separator and 2 cell cultures. The supernatant from the first culture, which contains the desired cytokines, is used to activate the second cohort of T cells.

Objective
To establish a preparative method of autologous memory T lymphocyte and use this T lymphocyte to treat hematologic malignancies and solid tumor.

Method
14 patients of hematologic malignancies and solid tumor had autolymphocyte therapy in 4 hospitals since 2002(Plasmacytoma1,NHL1, colon cancer3,HCC3,NSCLC1, nasopharyngeal carcinoma3, breast cancer1, Ovarian cancer1). These patients, including 11 male and 3 female, with a mean age of 55 (range, 25-71), were finally confirmed by pathology and histology autologouslymphokine, anti-CD3 antibody, IL-2. Cimetidine and Indomethacin induced peripheral blood mononuclear cell (PBMC) ex vivo to memory T lymphocyte by two steps. We tested memory T lymphocyte by flow cytometry before and after culture, we observed side effect during infusion.

Result
After culturing peripheral blood lymphocyte for 9 days, the number of cell and CD4+/CD45RO+T cell increased. The data demonstrated: PBMC before culture was 1.07-67.2×109(median was 2.16×109),the cell after culture was 2.0-6.5×109(median was 3.2×109),CD4+/CD45RO+T cell rate was 27.59-86%(median was 77.76%) before culture and 82.09-99.55%(median was 89.49%) after culture. The absolute number of CD4+/CD45RO+T cell increased. Among 14 patients after infusion, one patient who had no medicine before infusion had fever of 39°C, 4 patients had low-grade fever and the rest 9 patients had no side effect. Follow-up: 5 patients abroad had no follow-up. In 1 to 10 months after therapy, all patients were alive. 4 patients were in partial remission and 5 patients in stable stage.

Conclusion
Autologous memory T lymphocyte is a safe and an effective way to treat advanced-stage hematologic malignancies and solid tumor. The mechanism and long-tem effect need more research and observe.

Disclosures
No relevant conflicts of interest to declare.
Factor VIII-Fc Fusion Protein Shows Extended Half-Life and Hemostatic Activity in Hemophilia A Dogs.
Authors: Dumont Jennifer A , Kamphaus George D , Fraley Cara , Ashworth Tamera , Franck Helen , Merricks Elizabeth P. , Nichols Timothy C. , Bitonti Alan J 
Published: October 2019

Abstract
Abstract 545
A recombinant B-domain-deleted factor VIII-Fc (rFVIIIFc) fusion protein was created as an approach to extend the half-life of FVIII. The pharmacokinetics and pharmacodynamics of rFVIIIFc were evaluated in the Chapel Hill colony of hemophilia A dogs. These dogs have a severe hemophilic phenotype comparable to the severe form of human disease with F.VIII < 1%. A single intravenous dose (125 IU/kg) was administered to four dogs and immediately corrected the clotting to normal as measured by whole blood clotting time (WBCT) and aPTT. The WBCT remained below 20 min, the time consistent with FVIII:C > 1%, through approximately 96 h. The range of WBCT in our normal dogs is 8 to 12 min. The concentration of rFVIIIFc in the plasma was measured by ELISA and the terminal half-life was 15.7 ± 1.7 hr. Similar results were obtained when rFVIIIFc was measured using a FVIII-specific chromogenic activity assay (half-life was 15.4 ± 0.3 hr). The concentration vs. time curves were similar using both methods. The activity data were converted to ng/mL using the specific activity of the test article that was used to dose the animals, and these data correlated well with the ELISA data, thus demonstrating that the protein that was measured by ELISA was fully active.
Two of the dogs also received a single dose of recombinant B-domain deleted FVIII (rBDD-FVIII, ReFacto®), 114 IU/kg for one dog and 120 IU/kg rBDD-FVIII for the other, and then received rFVIIIFc (125 IU/kg) 72 hr later in a cross over design. Clotting was corrected to normal immediately after dosing with both rBDD-FVIII and rFVIIIFc (determined by WBCT and clotting activity measured using an aPTT assay). However, the WBCT normalization after rFVIIIFc lasted for approximately twice as long compared to rBDD-FVIII and the half-lives determined from the ELISA data for FVIIIFc (15.7 ± 1.7 hr) were twice those determined for rBDD-FVIII (7.0 hr and 6.7 hr). No adverse clinical signs were detected with any of the infusions. Therefore construction of an Fc fusion of FVIII produces a molecule with a defined mechanism of action that has an increased half life and the potential to provide prolonged protection from bleeding.

Disclosures:
Dumont: Biogen Idec (Syntonix Subsidiary): Employment. Kamphaus:Biogen Idec (Syntonix Subsidiary): Employment. Fraley:Biogen Idec/Syntonix Subsidiary: Employment. Ashworth:Biogen Idec (Syntonix Subsidiary): Employment. Bitonti:Biogen Idec/Syntonix Subsidiary: Employment.
Transferrin Receptor 2 Protein Is Expressed in Mitochondrial-Associated Lysosomes During Human Erythropoiesis.
Authors: Noh Seung-Jae , Wu Yun-Ping , Byrnes Colleen , Lee Y. Terry , Miller Jeffery L. 
Published: October 2019

Abstract
Abstract 628
Regulated expression of transferrin receptor 1 (TFR1) provides for the major mechanism of iron binding and absorption by endocytosis in erythroblasts. In contrast, the expression of transferrin receptor 2 (TFR2) in erythroid cells is not well understood. Fourteen-day cultures of human CD34+ cells were utilized to explore TFR2 gene and protein expression during erythropoiesis. Transcriptome analyses revealed an expression of the TFR2 gene on culture days 7 and 14. Protein analyses were performed with a TFR2 antibody that demonstrated a doublet band at 105 Kd in K562 and HepG2 cells, but no band in Jurkat cells. Western analyses of the primary erythroblasts demonstrated maximum TFR2 levels on culture days 6-8 coinciding with the onset of high-level glycophorin A expression and just prior to hemoglobin accumulation in the cells. Cellular localization of TFR2 was assessed by dual-staining confocal microscopy. More than 15 cells were analyzed for the calculation of correlation coefficients from 4-6 separate pictures per each sample. Unlike TFR1, expression of TFR2 on the plasma membrane was low or absent at all stages of erythroblast maturation. Expression of both proteins was detected in the endosomes throughout the cytoplasm on culture days 2-6. After culture day 6, TFR1 and TFR2 localization became divergent, with TFR2 localized almost exclusively to a single perinuclear compartment near the Golgi stack in the region of the centrosome. Co-localization experiments indicated that TFR2 was most highly co-localized with LAMP1, a lysosome marker. DMT1, the divalent metal transporter was also colocalized with the TFR2-lysosomes. The TFR2-lysosomes were additionally surrounded by and closely associated with mitochondria. Live cell imaging revealed dynamic interactions between the lysosomes and surrounding mitochondria. Pulse-chase experiments using Alexafluor 594-labeled transferrin (Tf) showed that endocytosed Tf was initially co-localized with TFR1. However, Tf was transported to the TFR2 localized region after a chase period of 10 minutes. In summary, TFR2 protein expression is highly regulated during erythropoiesis and localized to centrosomal lysosomes. These studies further suggest that iron regulation in erythroblasts includes trafficking to TFR2 and DMT1 containing lysosomes, which are dynamically associated with mitochondria.

Disclosures:
No relevant conflicts of interest to declare.
Evaluating the Response to Imatinib In Philadelphia-Positive Chronic Myeloid Leukemia (Ph+ CML): The Value of Major Molecular Response (MMolR) at 12 Months
Authors: Baccarani Michele , Rosti Gianantonio , Martinelli Giovanni , Castagnetti Fausto , Palandri Francesca , Gugliotta Gabriele , Amabile Marilina , Testoni Nicoletta 
Published: October 2019

Abstract
Abstract 668

The cytogenetic response is a confirmed early surrogate marker of the outcome of Ph+ CML patients treated with imatinib (Baccarani et al, JCO 2009;27:6041-51). Many reports and reviews highlight the value of MMolR, defined as a BCR–ABL value equal/less than 0.1% on the International Scale (Hughes et al, Blood 2006;108:20-37). The European LeukemiaNet recommendations use the BCR-ABL level for the definition of optimal response at 12 months (achievement of MMolR) and suboptimal response at 18 months (less than MMolR), but not for the definition of failure (Baccarani et al, JCO 2009; 27:6041-51). As the prognostic value of achieving a MMolR may increase with the introduction of 2nd generation tyrosine kinase inhibitors (TKIs) in the frontline treatment of Ph+ CML, we have reviewed and compared the cytogenetic and molecular data of 4 company–sponsored studies and 4 independent investigator–sponsored studies, for a total number of 2466 patients treated frontline with imatinib (Table 1). The CCgR rates at 12 months ranged between 49% and 88% (median 66%). The MMolR rates at 12 months ranged over a wider range, between 15% and 65% (median 33%). The ratio CCgR/MMolR ranged between 1.31 and 1.90 (median 1.60) in 5 out of 8 studies, while in the other 3 studies (Hammersmith, ENESTnd, and DASISION) the ratio was much higher, ranging between 2.35 and 4.00. Comparing Hammersmith, ENESTnd and DASISION studies to the other 5 studies (IRIS, TOPS, ELN, GIMEMA, and TIDEL), the CCgR rates were similar (median 64% vs. 67%, range 45–73% vs. 58–88%), while the MMolR rates were lower (median 22% vs. 40%, range 15–31% vs. 26–65%). These data cannot be used to argue that a lab, a dose of imatinib, or a study, is “better or worse” than the others, but higlight the consistency of CCgR worldwide and warns from overemphasizing the MMolR rate at 12 months for response evaluation and for treatment adaptation or modification.
Molecular studies sere performed: IRIS at 3 labs (Hammersmith, Adelaide; Seattle), Hammersmith at 1 lab, TIDEL at 1 lab (Adelaide), ELN at Bologna and many other labs, TOPS at 3 labs (Naples, Adelaide and Seattle), GIMEMA at 1 lab (Bologna), ENESTnd and DASISION at 1 lab (Portland).

Disclosures:
Baccarani: Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Research Funding; Wyeth: Consultancy, Research Funding. Rosti:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau. Martinelli:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy. Castagnetti:Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Gugliotta:Novartis: Honoraria.