bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can Body Mass Index Predict the Outcome of Diffuse Large B-Cell Lymphoma? - a Single-Center Retrospective Study in China
Authors: Li Tong , Liu Zhuo-Gang , Liang Pei-Qi , Wang Hong-Tao 
Published: October 2019

Abstract
Body mass index (BMI), as a rough indicator of obesity, has been increasing over the years, along with a high incidence of cardiovascular disease and many malignancies, including diffuse large B-cell lymphoma (DLBCL). However, the predictive prognostic value of BMI at diagnosis for the outcome of DLBCL is controversial. So far, the reported study population has rarely been Chinese. We aimed to assess whether BMI can predict the outcome of Chinese DLBCL patients.
We carried out a single-center retrospective study to assess the predictive value of BMI in the outcome of Chinese patients with DLBCL. Among a total of 207 patients who were newly diagnosed with DLBCL in our center between January 2008 and May 2015, 143 eligible patients were enrolled. These patients were stratified into two groups, 74 patients in the low BMI group (BMI<23.0kg/m2)and 69 patients in the high BMI group (BMI≥23.0kg/m2). We compared the baseline characteristics in the low and high BMI groups, and complete remission (CR), partial remission (PR) and progressive disease (PD) as primary response criteria in the two groups. Univariate and multivariate analyses were used to evaluate whether low or high BMI had an impact on progression-free survival (PFS) and overall survival (OS).
Well-known influence factors including age, Ca125, B2-microglobulin, international prognostic index, B symptoms, Ann Arbor stage and the use of rituximab were similar between the two groups, while gender was not (P<0.023) but did not act as a risk factor. Besides, drug dose did not vary by BMI. No association between BMI and primary response was observed. Patients in the higher BMI group were inclined to have better OS (p=0.008), but we did not find an association between BMI and PFS (p=0.069).
Higher BMI at diagnosis may predict a longer OS, especially for female patients but may not affect the outcome of primary response and PFS. Multi-center and prospective studies are warranted to see if this holds true for the general Chinese DLBCL population, and mechanistic investigations may lead to new treatment options.

Disclosures
No relevant conflicts of interest to declare.
Epidemiology Data of Patients with Chronic Myeloid Leukemia in West Central Mexico
Authors: Campos-Cabrera Virginia , Campos-Villagomez Jose-Luis , Campos-Cabrera Salvador , Campos-Cabrera Gregorio 
Published: October 2019

Abstract
Background:Chronic myeloid leukemia (CML) treatment in Mexican mestizos since the use of TKIs has been well described. Most of the studies only refers to the response rather than epidemiology. There are two large cohorts reported this years (Gad Med Mex 2016;152:208-212 and Clin Lymphoma Myeloma Leuk 2016;16:57-62), but all national information is not available.
Methods:Epidemiological data from samples referred to Laboratorios Fatima de Michoacan for identification of BCR-ABL translocation by chromosome or molecular analysis in patients with suspected chronic myeloid leukemia.
Results:77 positive samples for identification of BCR-ABL were analyzed. By physician indication 46 karyotype and 31 PCR. Male 40 and females 37, ratio 1.08/1. Age range from 15 to 87 years, mean 44.8. Three less than 19 years, thirteen from 20 to 29, twenty from 30 to 39 years, twelve from 40 to 49, twelve from 50 to 59, seven from 60 to 69, nine from 70 to 79 and one more than 80 years.
Conclusions: Compared with data from other Mexican CML studies (cited above) the age at diagnosis was similar: 44.8, 45.8 and 47.0 years; important to mention that in the three studies there are patients less than 15 years old; in the ratio M/F there was a difference: 1.08, 1.37 and 1.32. Compared to CLL epidemiology data that we presented last year in the 57thASH Annual Meeting (Blood 2015;126:5269), CML presented more than 20 years earlier, 66.0 to 44.8 years; M/F ratio is elevated in CLL 1.6 a 1; and CML is more frequent, 77 to 52 cases in CLL.

Disclosures
No relevant conflicts of interest to declare.
Emerging Potential Roles of Lysyl-Oxidase-like 2 Stimulates Cancer Associated Fibroblasts Promoting Myelofibrosis of Myeloproliferative Neoplasms
Authors: Liu Xiaoli , Xu Na , Pan Chengyun , Zhou Xuan , Liu Qifa , Feng Ru , Sun Jing , Zhou Hongsheng 
Published: October 2019

Abstract
Backgroud and objective: Myeloproliferative neoplasms (MPNs) are a group of clonal haematological disorders that characteristic with a multipotent haematopoietic stem cell transformation, often associating with the progression of myelofibrosis in the evolution course of disease. Progressive myelofibrosis finally turned out a high risk factor of transformation to leukemia and bone marrow failure. Cancer Associated Fibroblasts (CAFs) are recently thought to be a critical mediator in several hematological malignancies tumor microenvironment and associate with fibrosis. Lysyl-oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family that promote the crosslinking of collagens or elastins in the extracellular matrix and mediate epithelial-mesenchymal transition (EMT). Here, we want to verify CAFs mediating myelofibrosis and explore the potential role of LOXL2 association with CAFs in simulated vivo microenvironment.
Patients and methods:For bone marrow specimens, normal samples (n=19) and patients with polycythemia vera (PV) (n=21), essential thrombocythemia (ET) (n=32), and primary myelofibrosis (PMF) (n=9) were contrasted. Markers of CAFs including α-smooth actin(α-SMA), fibroblast activation protein(FAP), transforming growth factor-β1(TGF-β1) and LOXL2 were detected by quantitative reverse transcription-PCR(RT-PCR). we also detected α-SMA, FAP, LOXL2 and reticulin protein by western blot and immunohistochemical staining. For cell lines, α-SMA and FAP were measured after cocultured mesenchymal stem cell(MSCs) with recombinant human lysyl oxidase homolog 2 Protein(rhLOXL2) in hypoxic niche for 24, 48, 72 and 96 hours, respectively.
Results: Markers of CAFs displayed a differential pattern of expression in MPNs especially in PMF(P<0.010) compared with normal samples(P=0.023) according to RT-PCR. Among these markers, the expression of α-SMA is the highest. For western blot and immunohistochemical staining, we discovered the level of α-SMA, FAP and LOXL2 expression was associated with the grading of reticulin fibrosis in bone marrows. we also founded that α-SMA and FAP were significantly expressed after cocultured MSCs with rhLOXL2 in hypoxia for 96 hours, but there were no significant increase in gene and protein level expression with the prolonged exposure time.
Conclusion: Over expression of CAFs played a critical role in promoting bone marrow fibrosis. LOXL2 may be a key factor in stimulating MSC to CAFs and further promoting disease progression, which may provide a new target spot for further excavation of the pathogenesis of MPNs and looking for more effective targeted therapies.

Disclosures
No relevant conflicts of interest to declare.
Early Bortezomib Failure Predicts Shorter PFS: a Retrospective Analysis from 4 Victorian Centres
Authors: Bergin Krystal , Lew Thomas E , Chow Annie W.S. , Kopanidis Paul , Lim Hui Yin , Chan Kah Lok , Chai Khai-Li , Chua Chong Chyn , Reynolds John , Spencer Andrew 
Published: October 2019

Abstract
Aim: To compare patients with newly diagnosed multiple myeloma (NDMM) withbortezomib responsive and resistant disease (defined as <PR after 2 cycles) and assess the impact on clinical outcome particularly progression-free survival (PFS) and overall survival (OS).
Method: Retrospective review of all patients identified with NDMM treated with upfront bortezomib in four tertiary centres in Victoria, Australia between 1st of January 2009 and 1st of March, 2016. Bortezomib responsiveness was defined as achievement of PR or better after completing 2 cycles of any bortezomib containing therapy (total eight doses of bortezomib). Prior radiotherapy was allowed. Data were analysed via log rank tests for PFS and OS using SAS (V9.4) software. Predictors of bortezomib resistance were assessed by chi-square analysis.
Result: A total of 187 eligible patients were included (147bortezomib responsive and 40bortezomib resistant patients). Bortezomib resistance was associated with shorter median PFS, 27.4 (95%CI: 16.3, 30.8) vs 30.4 (95%CI: 23.4, 37.1) months (log-rank p= 0.047) with a median potential follow up of 27.4 vs 29.7 months in the resistant and responsive groups respectively. Estimated PFS at 12 months was 68.0% (95%CI: 50.3%, 80.5%) vs 88.3% (95%CI: 81.2%, 92.8%) and, at 24 months, 60.4% (95%CI: 41.7%, 74.7%) vs 60.0% (95%CI: 49.9%, 68.6%) in the resistant and responsive groups respectively, indicating non-constant hazard in the resistant group (see figure). Bortezomib resistance was not associated with higher ISS (ISS3 24% vs 15%, p=0.17), high riskcytogenetics (17p del ort(4;14)) (23% vs 23%, p= 0.99), MM sub-type (p= 0.63) or length ofbortezomib cycle (21 vs 35 day p= 0.56)). In responders (n=147), maintenance therapy was associated with improved PFS (p=0.021), and PFS at 24 months was, 70.7% (95%CI: 57.3%, 80.5%) vs 46.9% (32.0%, 60.5%) in those who received maintenance therapy and those who did not respectively. In non-responders (n=40) PFS at 24 months was 68.8% (95%CI: 35.7%, 87.3%) vs 54.9% (31.6%, 73.2%) in those patients who received maintenance therapy and those patients who did not respectively (p=0.84). Median OS has not been reached in either thebortezomib resistant or responsive groups however estimated OS at 24 months is 82.8% (95%CI: 62.8%, 92.7%) vs 89.5% (95%CI: 81.5%, 94.1%) in the resistant and responsive groups respectively.
Conclusion: Bortezomib resistance is a poor prognostic factor and is associated with a shorter PFS. Consideration of early therapy change, maintenance therapy and/or referral for assessment for allograft in eligible patients appears to be warranted.
Figure Figure.

Disclosures
No relevant conflicts of interest to declare.
VD Versus VTD Induction: Similar Efficacy in Controlling Disease in Transplant Eligible Multiple Myeloma Patients Outside Clinical Trials
Authors: Cocito Federica , Mangiacavalli Silvia , Ferretti Virginia Valeria , Cartia Claudio Salvatore , Ganzetti Maya , Cazzola Mario , Corso Alessandro 
Published: October 2019

Abstract
Autologous stem cell transplant (ASCT) remains the standard of care for Multiple Myeloma (MM) patients younger than 70 years old. The role of induction therapy is crucial within a program of high-dose therapy since deeper is the response before, higher is the outcome of transplant.
In this study, we analyzed a real life setting of patients treated with three different induction approaches: VAD (Vincristine-Adriamycin-Dexamethasone), VD (Bortezomib - Dexamethasone), and VTD (Bortezomib-Thalidomide-Dexamethasone) in terms of depth of response, 2 years therapy-free rate and toxicity.
One hundred and sixty-three MM patients (pts) were included in the analysis: 62 pts treated with VAD (38%), 44 with VD (27%) and 57 with VTD (35%). In VTD group 49 pts (86%) received Bortezomib subcutaneously. As shown in Table 1, patients of the three groups were similar for D&S stage (p 0.59), a higher rate of ISS stage 3 was observed in VAD group (p=0.019), patients in VTD group were significantly older (p=0.024), median follow-up was significantly lower in VTD pts (p<0.001). The overall response rates after induction were similar in all three groups (p=0.156), with higher rate of responses of good quality (CR+VGPR) for patients treated with Bortezomib-based combinations: VAD 24.2%, VD 52.3%, VTD 63.2% (p<0.001). No difference was observed between VTD and VD (p=0.258). A different pattern of responses was observed after transplant, VTD, in fact, was superior to VAD (p<0.001) and VD (p=0.012), while no difference was highlighted between VAD and VD (p=0.352). As a matter of fact, 2 years therapy-free rate were: 48% for patients treated with VAD vs 73% with VD vs 74% with VTD (p=0.189). Of note, however, bortezomib base therapy maintained its superiority with respect to VAD (p=0.03). No differences were observed between VD and VTD regimens in terms of toxicity of any grade and type (52.3% VD vs 52.6% VTD, p> 0.9), and of discontinuation rate (14% in VTD and 18% in VD, p=0.395). The incidence of all grades peripheral neuropathy (PN) was similar between VD and VTD (28.2% and 31.4% p=0.835), but grade 3-4 PN was significantly higher in VD group (no patients in VTD vs 18% in VD pts, p=0.078), probably due to different way of Bortezomib administration in VTD group (86% of pts received subcutaneous Bortezomib).
In this study, we confirm that Bortezomib-based regimens are better than VAD in terms of overall response rate, good quality responses and long-term disease control. VTD is superior to VD in terms of good quality responses after transplant but disease control at 2 years is similar.

Disclosures
Corso: Janssen-Cilag: Honoraria.
Robust Production of Cytomegalovirus pp65-Specific T Cells By a Fully Automated IFN-γ Cytokine Capture System
Authors: Kim Nayoun , Nam Young-Sun , Im Keon-Il , Lim Jung-Yeon , Jeon Young-Woo , Song YuneJin , Lee Jong Wook , Cho Seok-Goo 
Published: October 2019

Abstract
Cytomegalovirus (CMV) related diseases are a serious cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). As an alternative to antiviral drugs, CMV-specific cytotoxic lymphocytes (CMV-CTLs) can provide long-term CMV-specific immunity without major side effects. In this study, we apply the IFN-γ cytokine capture system (CCS) using the fully automated CliniMACS Prodigy device to rapidly produce CMV-CTLs. Five validation runs were performed using apheresis samples from randomly selected CMV-seropositive healthy blood donors. CliniMACS Prodigy automatically performed successive processes including antigen stimulation, anti-IFN-γ labelling, magnetic enrichment, and elution which took approximately 13 hours. The original apheresis samples consisted of 0.3% CD3+IFN-γ+ T cells which were mainly CD45RA+CD62L+ naïve T cells. Following IFN-γ enrichment, the target fraction contained 51.3% CD3+IFN-γ+ cells with reduction in naïve T cells and the selection of CD45RA-CD62L- and CD45RA+CD62L- memory T cells. Interestingly, the frequency of CMV pp65 specific CD3+ T cells was also increased by 1.7-fold. Furthermore, extended culture of isolated cells revealed efficient proliferation with sustained antigen-specific IFN-γ secretion and cytotoxicity against pp65 pulsed target cells. Therefore, we suggest IFN-γ CCS by CliniMACS Prodigy as a simple and robust approach to produce CMV-CTLs, which may be highly feasible and applicable for clinical use.

Disclosures
No relevant conflicts of interest to declare.
New Therapeutic Options: Alternates to Gene Therapy for Treating Hemoglobinopathies
Authors: De Franceschi Lucia 
Published: October 2019

Hemoglobinopathies are chronic, invalidating globally distributed hereditary red cell disorders, which impact patient survival and quality of life. Sickle cell disease (SCD) and β-thalassemias are the more frequent hemoglobinopathies worldwide. In both SCD and β-thalassemias, novel therapeutic strategies might be divided into (1) pathophysiology related therapies and (2) innovative curative therapeuties such as hematopoietic stem cell transplantation and gene therapy, the latter discussed in another presentation in this session. In the last two decades, studies have highlighted the biocomplexity of SCD and β-thalassemias and the need for the development of new therapeutic options targeting one or more of the mechanisms involved in their pathogenesis. In SCD, the pathophysiology related novel therapies might be divided into: (i)Molecules targeting sickling and red cell dehydration; (ii) Molecules targeting SCD vasculopathy and sickle cell-endothelial adhesive events; (iii) Molecules modulating SCD related oxidative stress. Since inflammatory vasculopathy is a key factor in SCD related organ damage, major efforts have been made to develop agents that interfere with SCD vasculopathy and adhesion events, involving sickle red cells, neutrophils and endothelial interplay. β-thalassemic syndromes are characterized by ineffective erythropoiesis, which plays a crucial role in anemia and in the development of extramedullar erythropoiesis. In β-thalassemic syndromes, pathophysiology related novel therapies might be divided into: (i) Agents reducing the ineffective erythropoiesis such the TRAP ligands, targeting the GDF11 pathway (sotatercept or luspatercept); (ii) Agents affecting Jak2 activation to reduce splenomegaly in β-thalassemia and (iii) Agents modulating hepcidin - erythropoiesis axis such as minihepcidins. The main goal of these molecules is to ameliorate the ineffective erythropoiesis resulting in increased hemoglobin levels with reduction of transfusion requirement, iron overload, and facilitating iron chelation therapy. This review highlights new therapeutic strategies in SCD and β-thalassemia and discusses future development, research implications, and possible directions toward future clinical trials.

Disclosures
De Franceschi: F. Hoffmann-La Roche Ltd, Basel, Switzerland: Research Funding.
The Effect of Homologous Marrow Transplantation on the Survival of Monkeys Following Sublethal Who1e-Body Radiation
Authors: NEWSOME FRANCES E. , OVERMAN R. R. 
Published: October 2019

Abstract
Homologous bone marrow given to the rhesus monkey 30 hours after LD 10 radiation dose of 550r increased the mortality rate expected from the radiation alone. The symptoms produced resembled those obtained at higher doses of radiation. The effects of marrow given 48 hours after radiation differed little from those produced by the radiation alone. It is suggested that the 30-hour injection elicited a more violent reaction or that the reaction occurred during a more decisive time in the process of recovery.
ON HOOKWORM ANEMIA
Authors: STRANSKY EUGENE , QUINTOS FLORENCIO N. 
Published: October 2019

Abstract
We have discussed three types or stages of blood changes in hookworm disease. Attention is directed to a severe irreversible aplastic anemia which occurs not infrequently in hookworm disease. The pathogenesis is obscure, but we believe that it is due to bone marrow exhaustion following continuous blood loss in the presence of various factors, including dietary deficiency.
The symptomatology, hematologic and bone marrow findings are described.
THE RELATIONSHIP BETWEEN HEPARIN DOSAGE AND CLOTTING TIME
Authors: JAQUES L. B. , RICKER ANN G. 
Published: October 2019

Abstract
1. The relationship between clotting time and heparin dosage has been studied in the dog.
2. On the addition of heparin to blood in vitro, a linear relation is found between heparin dosage and the logarithm of the clotting time obtained. The sensitivity of the blood sample to the action of added heparin is influenced both by the individual (coagulability of the blood before withdrawal) and by the technics of withdrawal and of determination of the clotting time. It is indicated that alterations in the latter may be used to extend the range of measurable hypocoagulability due to heparin. Incubation of heparin with blood for ten minutes increases its anticoagulant effect.
3. When moderate doses of heparin are injected intravenously, five to fifteen minutes are required for the clotting time to reach a maximum. No evidence of a biphasic response was obtained. The maximum clotting time obtained is greater than it is with the same amount of heparin added to the blood in vitro, due to the effect of incubation of heparin with blood on its anticoagulant activity. The in- terval required for the clotting time to return to normal is quite short, and with a given dosage is constant with different animals. Factors influencing the relation between duration of hypocoagulability and dosage are discussed.
4. A test has been devised to determine the sensitivity of the animal to the anticoagulant action of heparin. The clotting time response to certain concentrations of heparin added to the blood in vitro is determined. A fixed dose of heparin is then injected intravenously and the clotting time response is again determined. The response in vitro measures the sensitivity of the clotting system to heparin, while the in vivo response, when interpreted in the light of the in vitro response, measures the ability of the body to remove heparin from the circulation.
5. By means of this test, it has been determined that anesthesia with pentobarbital decreased the coagulability of the blood, urethane had no effect on coagulability, while the effect of ether was variable. The injection of india ink and evisceration caused a hypercoagulability, while removal of the kidneys had little effect.
6. When the sensitivity of the blood to the anticoagulant action of heparin was tested during these procedures, pentobarbital and nephrectomy had no effect, ether caused an increase in sensitivity, urethane a decrease. The injection of india ink and also evisceration markedly decreased the sensitivity of the blood to the anticoagulant action of heparin.
7. Anesthesia with pentobarbital, ether or urethane, the injection of india ink, removal of the kidneys, or removal of the gastrointestinal tract, had no effect on the duration of heparin action in the body.
RESPONSE OF TROPICAL SPRUE TO VITAMIN B12
Authors: SPIES TOM D. , SUAREZ RAMON M. 
Published: October 2019

Abstract
These findings show that the administration of vitamin B12 to patients with tropical sprue was followed by general clinical and hematologic improvement provided the dosage was adequate. A single dose of 4 micrograms administered in case 4 produced little or no change. The larger dosage of 10-25 micrograms administered in the other cases was accompanied by striking increase in strength and vigor and a decrease in the diarrhea; however, in no instance was a maximal dose given and these patients quickly tended to relapse clinically and hematologically. They could be relieved promptly again either by another injection of vitamin B12 or by a compound of folic acid. (The conjugated compounds of folic acid used in these cases were used for experimental purposes, and they produced the same hematologic response as that of folic acid per se.) Case 3, who had an excellent hematologic response after eating one serving of 400 grams of liver, is regarded as especially significant in that it suggests that, as powerful as vitamin B12 is as a therapeutic agent, it is more effective when given with liver. It is especially noteworthy that cases 1 and 2, who had three injections of vitamin B12, have had steady clinical and hematologic improvement. The reader should have in mind that a single injection of approximately 100 micrograms of vitamin B12 probably would be needed to produce a full hematologic response in persons so ill. This tentative appraisal would suggest that this therapeutic compound, per unit of weight, is more effective in treating human disease than any compound that yet has been used.