bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAG (cytarabine, aclarubicin, G-CSF) Regimen Is Effective and Well Tolerated in 367 Elderly Patients with AML in China and Japan: A Meta-Analysis
Authors: Wei Guoqing , Liu Delong 
Published: October 2019

Abstract
Abstract 4290

Background:
Current therapy is still unsatisfactory in elderly patients (pts) with acute myeloid leukemia (AML). CAG regimen (cytarabine, aclarubicin, G-CSF) has been commonly used in China and Japan for the treatment of elderly AML pts. The aim of this study is to summarize the data and to analyze the efficacy as well as the toxic effects of CAG regimen in elderly AML pts.

Methods:
The databases of PubMed, Wanfang Data, as well as American Society of Hematology (ASH) annual meeting abstracts were searched for articles published in English, Chinese and Japanese languages from January 1995 to December 2010. Eligible studies were relevant clinical trials of elderly AML pts treated with CAG regimen. Complete remission (CR) rate, odds ratio (OR) and 95% confidence intervals (CIs) of chemotherapy were compared through a meta-analysis using a random-effects or fixed-effects model.

Results:
19 trials with a total of 367 elderly AML pts were identified and included for analysis. Among the 367 AML pts treated with CAG, 266 pts were newly diagnosed AML, 54 pts were relapsed/refractory (R/R) AML. The AML status was not specified in the rest 47 pts. The CR rate for the 367 elderly AML pts was 52.0% (95% CI 46.8%-57.2%). Interestingly, no significant difference in CR rates was noted between the newly diagnosed (54.7%, 95% CI 48.6%-60.7%) and R/R AML pts (45.7%, 95% CI 32.4%-59.6%) (Q=1.332, p=0.248). Three studies compared the CR rates of elderly AML pts according to the karyotype. The CR rate was significantly higher in pts with intermediate (72.4%, 95% CI 58.0%-83.3%) cytogenetics than those with unfavorable one (35.7%, 95% CI 18.7%-57.2%) (Q=7.803, p=0.005). These elderly AML pts tolerated CAG well with low cardiotoxicity (0.73%, 2/273) and ED (8.48%, 29/342).

Conclusions:
CAG regimen induced high CR rates in elderly pts with new and relapsed/ refractory AML. This regimen was well tolerated with low cardiotoxicity and early death rate.

Disclosures:
No relevant conflicts of interest to declare.
Experimental Study of As2O3 Nanoparticles in the Therapy of Acute Promyelocytic Leukemia
Authors: Liu Ziling , Dong Xiaoyan , Li Wei , Ma Ning , Liu Mengmeng , Shan Jiying , Jin Fenglan , Fan Xiuli 
Published: October 2019

Abstract
Abstract 4302
This paper explores the preparation of As2O3 nanoparticles and examines their antitumor effects on NB4 cells. As2O3 nanoparticles were prepared using the sol-gel method and characterized by transmission election microscopy (TEM) and energy dispersive spectrometer (EDS). The results indicated that As2O3 nanoparticles prepared in our study were round or elliptical, well dispersed, and about 40 nm or less than 10 nm in diameter. The antitumor effects of As2O3 nanoparticles at various concentrations were analyzed by the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry (FCM) and were compared with those of traditional As2O3 solution. At the same concentration and incubation time (48 h), the survival rate of cells treated with As2O3 nanoparticles was significantly lower than that of cells treated with As2O3 solution. The inhibition rate under both treatments was time- and dose-dependent. In addition, at the some concentration and incubation time, the apoptosis ratio of cells treated with As2O3 nanoparticles was significantly higher than that of cells treated with As2O3 solution. Furthermore, As2O3 nanoparticles resulted in a greater reduction in the expression of the anti-apoptotic protein Bcl-2 compared with As2O3 solution. In conclusion, AS2O3 nanoparticles, prepared by sol-gel method, produce a stronger cytotoxic effect on tumor cells than As2O3 solution, possibly through inhibiting Bcl-2 expression.

Disclosures:
No relevant conflicts of interest to declare.
Antifungal Prophilaxis with Low Dose Amphotericin B Lipid Complex In Patients with Acute Myeloid Leukaemia: A Single Centre Experience
Authors: Veggia Barbara , Saltarelli Francesca , Montefusco Enrico , Conte Esmeralda , Antolino Giusy , Porrini Raffaele , Monarca Bruno , Ferrari Antonella 
Published: October 2019

Abstract
Abstract 4303

INTRODUCTION
Invasive fungal infections (IFI) represent an important cause of mortality and morbidity in patients with Acute Myeloid Leukemia (AML) undergoing intensive chemotherapy. A prophylactic antifungal therapy is often administered during intensive chemotherapy, however the optimal antifungal prophylaxis protocol is still unknown. Amphotericin B lipid complex (Abelcet®) has been commonly used as a standard treatment for IFIs caused by Aspergillus and Candida, but its effectiveness in prophilaxis has not been clearly estabilished.

METHODS
From September 2010 to April 2011 we treated six patients with newly diagnosed AML using low dose amphotericin B lipid complex as antifungal prophilaxis. Patients observed were three females and 3 males, median age was 54 years (range 21–74 years) and they were all fit to receive intensive chemotherapy. Three patients older than 60 years received Fludarabine based chemotherapy regimen during both induction and consolidation. Three patients aged less than 60 years old were treated using a chemotherapy protocol based on Citarabine, Daunorubicin and Ethoposide association. One patient in this group also underwent BuCy conditioned autologous stem cell transplant. Amphotericin B lipid complex was administered intravenously at 100 mg once a day. Antifungal prophilaxis was started when the absolute neutrophil count was ≤ 500 cells/μ l and was continued until neutrophils recovery was ≥ 500 cells/μ l, without any evidence of IFI.

RESULTS
Five patients did not experience any proven fungal infection during all treatment. Anyway one patient died during induction due to a severe bacterial lung infection. One patients discontinued antifungal prophylaxis due to extensive skin rash during the second infusion of the drug. Amphotericin B lipid complex was otherwise well tolerated by patients. One patient was diagnosed with lung aspergillosis infection by evidence of galattomannan positivity on BAL and a lung CT scan showing a single nodular escavated lesion on left upper lobe; subsequentely he was successfully treated with voriconazole.

CONCLUSIONS
In our experience, Amphotericin B lipid complex showed to be an effective and safe antifungal prophylaxis for newly diagnosed AML patients. Further clinical studies are certainly required to obtain definitive data.

Disclosures:
No relevant conflicts of interest to declare.
Generation and Optimization of a Chimeric Antigen Receptor Against CD22: A New Immunotherapeutic Agent for Treating B Lineage Leukemia and Lymphoma
Authors: Orentas Rimas J , Haso Waleed , Morgan Richard A. , Pastan Ira , Mackall Crystal L 
Published: October 2019

Abstract
Abstract 4313
CD22 is expressed on a number of hematologic malignancies. A recombinant immunotoxin composed of an anti-CD22 Fv fused to a 38 kDa fragment of Pseudomonas exotoxin A (Moxetumomab pasudodtox, HA22) is currently being evaluated in the treatment of B cell malignancies. We used the Fv sequence to construct a series of chimeric antigen receptors (CARs) to determine the optimal affinity, domain structure, and signaling required for optimal anti-leukemic activity. The original anti-CD22 binding domain, BL22, or a newer generation high-affinity domain, HA22, were fused to transmembrane and signaling sequences derived from the TCR zeta-chain, CD28, and CD137. In some constructs we extended the binding domain away from the membrane using constant domains from IgG (CH2CH3). Retroviral gene vectors were used to transduce activated primary T cells with CAR constructs. We found: HA22 Fv, 2 as opposed to 3 signaling motifs, and non-CH2CH3 containing CARs were superior in short-term in vitro tumor cell cytolysis assays, indicating that Fv affinity, signaling, and 3-D structure of the CAR all impact the anti-leukemic effectiveness of CARs. Finally, direct comparison to CD19-specific CAR showed an equivalent or superior killing activity in 2 out of 3 ALL lines tested. Using Scatchard analysis to define the number of CD22 moleules on the surface, the ALL line with the lowest number of CD22 molecules is also the least able to be killed by CAR-transduced T cells. The supeior lytic activity of CD19-CAR for this single cell line was due to preservation of high levels of CD19 at the cell surface. We are currently testing the in vivo activity of anti-CD22 CAR in an immunodeficient mouse model bearing human cell lines and primary patient-derived ALL. Our results indicate that CD22-CAR should be developed for the immunotherapy of CD22+ hematologic malignancies.

Disclosures:
No relevant conflicts of interest to declare.
The Analysis of Patients with Refractoriness to Platelet Transfusion Due to Anti-HLA Antibodies During the Treatment of Acute Leukemia
Authors: Takada Satoru , Koya Hiroko , Yuzuriha Akinori , Shimizu Hiroaki , Hatsumi Nahoko , Sakura Toru 
Published: October 2019

Abstract
Abstract 4339

Background and aim:
Refractoriness to platelet transfusion is one of complications during the treatment of acute leukemia. The major reason is destruction of transfused platelets by anti-human leukocyte antigen (HLA) antibodies to HLA on donor’s platelets. We investigated retrospectively the incidence and characteristics of patients with refractoriness to platelet transfusion due to anti-HLA antibodies during the treatment of acute leukemia.

Method:
From 2000 to 2010, 348 acute leukemia patients underwent chemotherapy at our hospital. Among them, we surveyed 325 patients who received platelet transfusions more than five times. Examination of anti-HLA antibodies was performed when clinically an attending physician suspected that platelet transfusion was not effective. The existence of anti-HLA antibodies were tested both lymphocyte cytotoxicity test (LCT) and anti human immunoglobulin-LCT (AHG-LCT).

Result:
Of the 325 patients, males were 186, and female were 139. Two hundred sixty-three patients and 62 patients suffered from acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL), respectively. The median age of all patients was 57 (15–86) years. All patients had received red blood cell and platelet products from which leukocytes were removed by filtration. Of all patients, 23 (7.1%) were positive for anti-HLA antibodies. The median age of patients with anti-HLA antibodies was 57(24–76) years. The number of male and female were 2(8.7%) and 21 (91.3 %), respectively. All female patients with anti-HLA antibody had a history of delivery. 8.3 % of AML patients and 1.6% of ALL patients were positive for anti-HAL antibodies.The median number of platelet transfusions until the presence of anti-HLA antibodies was 11 (4–48). The median date of anti-HLA antibodies detection was 27(8–263) days after first platelet transfusion. After detection of anti-HLA antibodies, all patients with anti-HLA antibodies received HLA-matched platelets, and fatal bleeding was not seen. History of delivery (p<0.001), AML (p=0.0147) and age over 50 years (p=0.0490) were risk factors for the presence of anti-HLA antibodies. The presence of anti-HLA antibodies had no impact for the survival (p=0.6033).

Conclusion:
During chemotherapy for the treatment of acute leukemia, 7% of patients suffered from refractoriness to platelet transfusion due to ant-HLA antibodies. The frequency was low compared with other blood disorders. Elderly AML patients with a history of delivery tended to produce anti-HLA antibodies. Patients with anti-HLA antibodies could obtain similar outcomes by using HLA-matched platelets, comparing with patients without anti-HLA antibodies.

Disclosures:
No relevant conflicts of interest to declare.
ADAMTS13 Cleavage of Von Willebrand Factor (VWF) in Commercial Concentrates and Effect on VWF Function
Authors: Fuchs Birte , Solecka Barbera , Kröning Mario , Kannicht Christoph , Schwartz Bruce A. 
Published: October 2019

Abstract
Abstract 4354

Objective:
The characteristic multimeric pattern of plasmatic VWF results from asymmetric cleavage by ADAMTS13. Regulation of VWF multimer distribution is critical for its physiological function. In human plasma, VWF multimer gels reveal species of various multimeric sizes with flanking satellite bands (triplets). The faster and slower migrating bands encompassing a VWF multimer lack one N-terminal fragment or possess an additional N-terminal fragment, respectively. Defects in VWF secretion, impaired assembly of multimers, or increased proteolysis can cause von Willebrand Disease (VWD). Distribution of VWF triplet bands is significantly altered in some plasma-derived VWF concentrates. The impact of triplet structure on VWF function has not been investigated so far.

Methods:
Four commercially available VWF concentrates were analyzed for ADAMTS13 content as well as VWF multimer- and triplet structure using agarose gel electrophoresis. ADAMTS13 activity was quantified by fluorescence resonance energy transfer (FRET) assay. Samples composed of different VWF triplet distribution but comparable multimers were obtained by heparin affinity chromatography. Platelet adhesion under flow was determined using a flow-chamber model.

Results:
VWF concentrates markedly differed with respect to their content of ADAMTS13 antigen and activity. A higher content of ADAMTS13 correlated with an altered triplet structure reflected by an increased presence of the faster migrating triplet band, indicating VWF proteolysis. VWF-mediated platelet adhesion under flow over time was increased using a VWF fraction predominantly containing the slower migrating triplet band.

Conclusion:
These findings suggest that an intact triplet structure has an impact on platelet adhesion at physiological high arterial shear rate conditions. The relevance of VWF N-terminal domains for platelet binding and potential clinical consequences of enhanced proteolysis in commercial concentrates has to be further evaluated.

Disclosures:
Fuchs: octapharma: Employment. Solecka:Octapharma: Employment. Kröning:Octapharma: Employment. Kannicht:Octapharma: Employment. Schwartz:Octapharma: Employment.
Successful Delivery of Patients with FXIII Deficiency on Prophylaxis in Iran
Authors: Naderi Majid , Eshghi Peyman , Cohan Nader , Yaghmaei Minoo , Miri Moghaddam Ebrahim , Sadeghi-Bojd Simin , Karimi Mehran , Hoorfar Hamid , Lak Manijeh , Narouie Behzad 
Published: October 2019

Abstract
Abstract 4363

Introduction
Coagulation factor XIII (FXIII) deficiency is a rare bleeding disorder with a general frequency of 1 in 2 million populations. Life-long bleeding tendencies, umbilical bleeding, defective wound healing and habitual abortions are the most important clinical problems in this patients.For prevention of abortion and pregnancy loss in severe FXIII-deficient women, replacement and prophylaxis with a source of FXIII throughout pregnancy is essential.The acceptance level of plasma FXIII level for successful delivery is above 10% as a result the administration of FXIII concentrate 250 IU weekly until 22 weeks gestation and 500 IU from 23 weeks is recommended to maintain this plasma level. The aim of this study was to evaluate the bleeding score and rate of successful delivery in Iranian FXIII deficient pregnant women on regular prophylaxis.

Material and methods
A total of 17 FXIII deficient Iranian women with age range 18–35 years old (mean 24 years old) were enrolled in this study. The first record bleeding episodes were cord bleeding in 10 patients, echymosis in 4 patients, hemarthrosis in 1 patient, hematoma in 1 patient and CNS bleeding in 1 patient. All patients had history of abortion (one abortion in 12 patients, 2 abortions in 2 patients and 3 abortions in 2 patients) except one patient. All of patients were on regular prophylaxis (10 IU every 2 weeks) for 24–62 months, every 4 weeks before pregnancy and every 2 weeks during pregnancy. The patients were followed for any bleeding episodes and also evaluated for bleeding score before and after prophylaxis according on standard form.

Results
The monochloroacetic acid test was normal in all patients during prophylaxis.
The bleeding score was significantly decreased from 11–16 (mean 12) to 1–2 (mean1.5) starting prophylaxis. Two bleeding episodes were recorded in 2 patients, one subject in 11 patients and 3 patients didn’t experience any bleeding episodes. All of patients had successful delivery at 36 weeks gestation without any significant coagulation complications.

Discussion
Pregnancy loss is a main complication in women with FXIII deficiency and prophylaxis is critical for pregnancy maintenance in these patients. In this study we experienced a successful pregnancy maintenance and delivery in Iranian women with FXIII deficiency. It is recommended to precise detection and diagnosis of FXIII in women with coagulation disorders for appropriate prophylaxis and prevention of pregnancy loss.

Disclosures:
No relevant conflicts of interest to declare.
Serial D-Dimer in Pregnancy Women with a History of Fetal Loss Syndrome and Invitro Fertilization
Authors: Atmakusuma Tubagus Djumhana , Muharam Raden 
Published: October 2019

Abstract
Abstract 4366

Background
We have reported in abstract P-Th-374 in a 2011 Kyoto ISTH Congress that an increased level of D-dimer in combination with umbilical artery systolic diastolic (UASD) ratio can be used as a timing to start with prophylactic anticoagulants In women with pregnancy failure, regardles of the antibody antiphospholipids (APAs) level, history of fetal loss syndrome or invitro fertilization (IVF).
The question is: Are there any differences of a serial D-dimer level if is compared to the APAs level, history of fetal loss syndrome and IVF?.

Methods.
A retrospective Cohort study was conducted on a total sampling subjects of pregnancy women who visited two hospitals in Jakarta, Indonesia, at a periode of January 2009 – December 2010. Serial D-dimer using chromogenic assay method (cut off normal level < 500 ng/ml) was tested during antenatal and post partum period. The data were analysed to compare a mean D-dimer with the level of APAs (ACA IgG/IgM, AntiB2GP1 IgG/IgM) tested using ELISA method, a history of fetal loss syndrome and IVF conception

Results
Of 83 pregnant women,19 women with high level of APAs (subgroup 1) showed a mean D-dimer level as follows: Trimester I: 892.15 ± 785.15 ng/ml, trimester II: 782.59 ± 440.53 ng/ml, trimester III:1282.62 ± 601.22 ng/ml, post partum 1367.45 ± 581.19 ng/ml; 31 women with normal APAs (subgroup 2) showed: Trimester I: 666.23 ± 396.24 ng/ml, trimester II: 896.66 ± 396.24 ng/ml, trimester II: 896.66 ± 496.32 ng/ml, trimester III: 1313.45 ± 850.20 ng/ml, post partum: 1991.75 ± 1388.70 ng/ml; 33 women with no data of APAs (subgroup 3) showed: Trimester I: 568.47 ± 482.70 ng/ml, trimester 2: 797.95 ± 934.59 ng/ml, trimester III: 966.89 ± 862.10 ng/ml, post partum: 1078.50 ± 836.29 ng/ml
Of 83 pregnant women, 47 women who have experienced 1 or ≥ 1 abortion or IUFD (subgroup 4) showed D-dimer level as follows: Trimester I:493.09 ± 385.89 ng/ml, trimester II: 740.23 ± 564.99 ng/ml, trimester III: 859.05 ± 549.88 ng/ml, post partum 1342.59 ± 1264.09 ng/ml. Meanwhile, 36 women who have no history of fetal loss (subgroup 5) showed: Trimester I: 892.17± 593.47 ng/ml, trimester II: 930.57± 807.02 ng/ml, trimester III: 1439.71 ± 932.12 ng/ml, post partum 1695.16 ± 1131.56 ng/ml.
Of 83 pregnant women, 10 women who became pregnant after embryo transfer of IVF (subgroup 6) showed: Trimester I: 493.09± 385.895 ng/ml, trimester II: 740.23± 564.99 ng/ml, trimester III:859.05 ± 549.88 ng/ml, post partum 1342.59 ± 1264.09 ng/ml.

Conclusion
Either in subgroup 1, 2, 3,4,5 and 6 mean D-dimer tend to increase from trimester I to trimester II and from trimester II to trimester III, except in subgroup 1 from trimester I to trimester II of pregnancy. Meanwhile, all groups showed a higher mean D-dimer post partum compared to antenatal period.

Disclosures:
No relevant conflicts of interest to declare.
Chemotherapy Plus Hematopoietic Growth Factor for Refractory Paroxysmal Nocturnal Hemoglobinuria: Diminishing PNH Clone and Stimulating Hematopoisis
Authors: Shao Zonghong , Dong Xifeng , Fu Rong , Qu Wen , Liang Yong , Wu Yuhong , Wang Guojin , Liu Hong , Song Jia , Wang Xiaoming , Xing Limin , Ruan Erbao , Guan Jing , Wang Jun , Wang Huaquan 
Published: October 2019

Abstract
Abstract 4376

BACKGROUND
Even complement inhibitor against C5 Eculizumab has been used in the treatment of paroxysmal nocturnal hemoglobinuria (PNH) acting as a “dam” protecting PNH clone and storing higher risk of hemolysis. So we carried out a study to investigate the efficacy and safety of chemotherapy plus growth factors, a traditional treatment for malignant hematological diseases, aiming at diminishing PNH clone and stimulating hematopoisis, in patients with refractory and relapsed PNH.

METHODS
10 patients were enrolled in this study. These patients were admitted into General Hospital affiliated to Tianjin Medical University(TMU) between 2006 to 2010, receiving either DAG (DNR 40mg/d, d1–2; 20mg/d, d3; Ara-C 100mg/d, d1-5; G-CSF until WBC return normal) or HAG (HHT 2–3mg/d, d1-5; Ara-C 100mg/d, d1-5; G-CSF until WBC return normal) regimen chemotherapy intravenously every 4 weeks for several cycles. The primary end points were the improvement of hemoglobin levels, decreased proportion of PNH clone and dosage of corticosteroid. Biochemical indicators of intravascular haemolysis and adverse events were also assessed.

RESULTS
All patients responded well. Overall improvement for anemia was achieved, transfusion independence(HB can keep more than 6g/L without transfusion) was achieved in 4 patients, hemoglobin levels reached normal gradually in 1 of them, 2 patients got prolonged transfusion interval, another 4 patients did not need transfusion all the time. Elevation of hemoglobin from (58.1±12.12) g/L to (90.20±21.55) g/L (P=0.000) was achieved for the 10 patients. The dosage of corticosteroid decreased significantly from (45.84±19.05)mg to (13.00±6.75)mg (P=0.000). The results of flow cytometry demonstrated that CD59− and CD55− erythrocytes and granulocytes in peripheral blood decreased significantly in 8 patients [(20.87±11.68)% vs (7.97±10.02)%, P=0.004 for CD59− erythrocytes; (63.76±25.36)% vs (28.44±23.50)%, P=0.002 for CD55− erythrocytes; (68.25±26.05)% vs (59.53±24.60)%, P=0.007 for CD59− granulocytes; (81.47±26.13)% vs (68.14±26.53)%, P=0.003 for CD55− granulocytes]. Indicators for haemolysis also improved. In 10 patients, apart from 1 patient with normal IBIL and TBIL all the time, IBIL decreased significantly from (36.8±29.2) U/L at baseline to (18.1±12.4) U/L (P= 0.015). Free hemoglobin level, Rous test, Ham ‘s test were carried out only in some of the patients and results of which were also encouraging. No patients died during chemotherapy; most common adverse events were infection, nausea, vomiting and fatigue. The duration of bone marrow depression ranged from 10 to 33 days.

CONCLUSIONS
DAG/HAG regimens Chemotherapy was an effective, safe and promising therapy for PNH.

Disclosures:
No relevant conflicts of interest to declare.