bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addition of Hemoglobin Level Into the Prognostic Scoring System Together with White Blood Cell and Platelet Count Provides Better Prognostic Stratification for Treatment-Related Mortality and Overall Survival, but Not for Relapse Risk In Adult Patients with Acute Promyelocytic Leukemia
Authors: Yi Jun Ho , Jung Chul Won , Han Boram , Lee Ha Yeon , Jang Jun Ho , Kim Kihyun , Kim Hyeoung Joon , Kim Yeo-Kyeoung , Lee Won-Sik , Joo Young-Don , Kim Min Kyoung , Hyun Myung Soo , Kim Hawk , Park Jae Hoo , Kim Dong Hwan (Dennis) 
Published: October 2019

Abstract
Abstract 4371

Background:
Although the introduction of all-trans retinoic acid (ATRA) and combined chemotherapy improved clinical outcomes of acute promyelocytic leukemia (APL), treatment failure still occur due to early death or disease relapse. The PETHEMA study suggested that the risk adopted stratification of disease risk into 3 groups (low, intermediate and high risk) according to the white blood cell (WBC; 10×109/L) and platelet counts (40×109/L) could improve treatment outcomes of APL patients. However, this stratification system needs to be validated in an independent cohort of patients. The current study attempted to validate the prognostic system based on WBC and platelet counts, hemoglobin level, risk stratification system by PETHEMA and proposed prognostic system consisting of WBC and platelet counts and hemoglobin level.

Methods and patients:
Total of 164 patients was included retrospectively from 5 institutes in Republic of Korea. In patients receiving Idarubicin/ATRA based combination chemotherapy. Consolidation therapy was given with Idarubicin monotherapy in 79 patients, or Idarubicin plus cytarabine in 42 patients.

Result:
With median follow-up of 2.94 years, the CR rate following remission induction treatment was 83.9% in overall patients, while the 3 years OS, TRM and relapse rate was 77.6±3.5%, 20.4±3.3, and 9.6±3.1%, respectively. The combined prognostic system provided better stratification of APL patients according to their prognosis compared to single variable comparison such as WBC counts, platelet counts or hemoglobin level. In addition, the risk stratification system by PETHEMA could predict OS (p=0.06) and TRM (p=0.05), but not CR rates (p=0.1) or relapse (p=0.7). However, the proposed 3 score prognostic system could provide better stratification of APL patients in term of the CR rates (p=0.01 vs 0.1 between 3 score system vs PETHEMA risk stratification), OS (p=0.02 vs. 0.06) and TRM (p=0.006 vs 0.05), but not of relapse risk (p=0.9 vs 0.7).

Conclusion:
This retrospective study suggested that the proposed 3 score prognostic system could provide better stratification of APL patients in term of the CR rates, OS and TRM, but not of relapse the risk. Further study will be needed to reach a clear conclusion of better prognostic stratification of APL patients with large number of patients.

Disclosures:
No relevant conflicts of interest to declare.
Imaging Thromboembolism with 99mtc Labelled Chimeric Monoclonal Anti-Platelet Glycoprotein Iiia Antibody Fragment chSZ21F(ab)2: Evaluation In Beagle Canines
Authors: Ji Shundong , Fang Wei , Dong Ningzheng , He Zuoxiang , Ruan Changgeng 
Published: October 2019

Abstract
Abstract 4387

Abstract

Purpose
A mouse/human chimeric monoclonal antibody F(ab)2 fragment, with high affinity for platelet glycoprotein IIIa was labelled with99mTc (99mTc-chSZ21F(ab)2), and evaluated in canine to image experimental venous thromboembolism (deep vein thrombosis [DVT]) and pulmonary embolism (PE).

Methods
ADP-stimulated platelet aggregation was performed to determine the affinity and specificity of chSZ21F(ab)2 to the GPIIb/IIIa receptor on plates of human or canine. ChSZ21F(ab)2 was modified with 2-iminotholane and incubated with 99mTc-glucoheptonate for imaging of 24-h-old DVT and PE in a canine model. Animals were imaged for up to 3 h after injection, heparinized, and sacrificed. Lungs and other tissues, including blood and normal lungs, were harvested and, concurrently, 99mTc was counted for determination of target to tissue ratios and the percentage of injected dose per gram of tissue.

Results
The concentration of chSZ21F(ab)2 required to inhibit 50% of platelet aggregation (IC50) in platelet-rich plasma was 11.6±7.9 nM for human and 24.9±18.8 nM for canine. In vivo, focal uptake was observed in planar images as early as 30 min (DVT), and 60 min (PE) after injection. Lesion uptake of 99mTc-chSZ21F(ab)2 at 3 h after injection was calculated in terms of percentage injected dose per gram (%ID/g) of tissue and averaged 0.076%ID/g PE and 0.083%ID/g DVT. Lesion-to-background ratios averaged 12.8 (PE-to-lung), 7.2 (DVT-to-blood), and 117.0(DVT-to-muscle).

Conclusion
99mTc-chSZ21F(ab)2 with its modest affinity and high DVT and PE uptake is a promising agent for imaging vascular thrombosis.

Disclosures:
No relevant conflicts of interest to declare.
aPTT Versus Anti Xa Monitoring of Unfractionated Heparin - a Retrospective Review of Clinical Outcomes
Authors: Dhami Sabina , Lorinsky Michael , Johnson Susan , Smith Michael , Healy Abigail , Kapur Nisha , Taylor Roseleigh , Slater Dennis E , Dhami Mandeep S 
Published: October 2019

Abstract
Abstract 4391
In May 2008, The William W. Backus Hospital changed the unfractionated heparin dosing protocol and the monitoring parameter for the treatment of thromboembolic disease. The original protocol utilized the Rashke's method (Bolus dose 80 units/kg and initial infusion of 18 units/kg/hour) monitored with aPTT (Therapeutic range 61–80.9 seconds). The newer protocol is a novel model utilizing a bolus dose of 26 units/kg and initial infusion rate of 15 units/kg/hour, calculated using the methodology designed by Rosbourough et al monitored with anti-Xa (Therapeutic range 0.3–0.7 anti Xa units). This is a retrospective study comparing of the efficacy and safety of each protocol.

Methods:
Data abstraction was completed through electronic medical record review of two hundred patients. Time point 0 was the date of changing to the new protocol. One hundred patients in reverse chronological order were reviewed for the original protocol and one hundred patients in chronological order with the new protocol. Data included demographics, duration of time prior to achieving therapeutic parameters, number of dosage changes, diagnosis of cancer, bleeding events and recurrent thrombotic events. Unpaired Student t tests were utilized to statistically analyze the differences between the cohorts.

Results:

Conclusion:
Both methodologies achieved therapeutic levels rapidly. The Rosbourough method required statistically significant less dosage changes when compared to the Rashke method. The incidence of major and minor bleeding was similar between the two dosing algorithms. Although not statistically significant, the incidence of recurrent thromboses was numerically higher with the Rosbourough method compared to Rashke method. This is concerning and suggests that the higher loading dose may be more appropriate. A prospective comparison of these two monitoring methods using Rashke dosing is planned.

Disclosures:
Off Label Use: Discuss alternative dosing and anti Xa monitoring of unfractionated heparin infusion.
(AVK) Anti Vitamin K Treatment In patients with Fontan Surgery
Authors: Infante Maria Stefania , Izquierdo Cristina Pascual , Lopez Fernando Carretero , Ramirez Jose Manuel Sanchez , Huerta Ana Maria Rodriguez , Rus and Jose Luis Diez Martin Gloria Perez 
Published: October 2019

Abstract
Abstract 4397

OBJECTIVES
Thrombotic events have been reported as a major cause of morbidity after the Fontan procedure. There is no consensus about the type and duration of postoperative anticoagulation prophylaxis, due to the high risk of bleeding complications, the difficulties in monitoring and the questionable therapeutic compliance in children. In spite of the lack of long term prospective studies in this situation, the ACCP has recommended in their guidelines OAT following Fontan or Glenn operation for at least 6 months. This has also been our practice in our institution during the period of study.

AIM OF THE STUDY
To analyze the efficacy and complications of OAT in our pediatric patients after undergoing the Fontan operation.

METHODS
Retrospective chart review of all the children treated with OAT in our institution between 1995 and 2009. All patients were treated initially with acenocumarol 0,2 mg/kg, except the Fontan patients, who received 0,1 mg/kg. Target INR was 2–3 for all patients.
The Mann-Whitney test was used to compare the rate of complications, and the percentage of visits out of target INR between the Fontan patients and the rest of the cohort.

RESULTS
There were 61 children (26 female/35 males) aged between 1 month and 17 years, who received OAT with a range of follow up between 4 months and 14 years: 27 after Fontan operation (Group A), an 34 for other reasons (Group B: n=13 non prothetic valve cardiopathy, n=21 treatment of thromboembolic disease).
The average follow-up was similar in both groups (median of 6.5 months in group A vs.7.5 months in group B). There were few complications: 1 mild epistaxis and 1 thrombotic event in group B, and none in group A. There were no differences in the proportion of controls in normal range between both groups; there was a moderate proportion of controls outside the target range of INR, with higher distribution below the range than above the range. The median dose used to achieve the target INR was 0.3 mg/kg/d in Group A and 0.4 mg/kg/d in Group B.

CONCLUSIONS
Oral Anticoagulant therapy is safe and effective in pediatric patients,with very low rates of thrombotic or hemorragic complications including those undergoing the Fontan surgery. There were not any differences between both groups in any of the analizyed parameters.

Disclosures:
No relevant conflicts of interest to declare.
Eltrombopag Can Stimulate Trilineage Hematopoiesis In Patients with Refractory Severe Aplastic Anemia
Authors: Olnes Matthew J. , Tang Yong , Soto Susan , Sloand Elaine M , Scheinberg Philip , Young Neal S. , Dunbar Cynthia E. 
Published: October 2019

Abstract
Abstract 4427
Severe aplastic anemia (SAA) is characterized by trilineage marrow hypoplasia and a paucity of hematopoietic stem cell progenitors. SAA is treated with immunosuppression or allogeneic stem cell transplantation (SCT), with a successful outcome in a majority. However, 20–40% of patients without a suitable donor for SCT do not respond to immunosuppression and may have persistent severe thrombocytopenia. Thrombopoietin (TPO) is the principal regulator of platelet production, and it exerts its effects through binding the megakaryocyte progenitor TPO receptor mpl, which stimulates production of mature megakaryocytes and platelets. Eltrombopag, a small molecule TPO mimetic that binds to mpl, increases platelet counts in healthy subjects, and in patients with chronic immune thrombocytopenic purpura. Both TPO and eltrombopag stimulate more primitive multilineage progenitors and stem cells in vitro. Patients with SAA and thrombocytopenia have very elevated TPO levels; nevertheless, we asked whether pharmacologic doses of eltrombopag could stimulate hematopoiesis in these patients without other options. We are conducting a pilot phase II study of eltrombopag in SAA patients with severe thrombocytopenia refractory to immunosuppressive therapy. Consecutive eligible adult patients were treated with oral eltrombopag at an initial dose of 50 mg daily, with escalation to a maximum dose 150 mg daily, with the goal of maintaining a platelet count of >20,000/uL above baseline. Treatment response was measured after three months and was defined as platelet count increases to 20,000/uL above baseline, or stable platelet counts with transfusion-independence for a minimum of 8 weeks. Nine patients have been enrolled and six are evaluable for response to date. Two patients did not respond to treatment. Three patients achieved platelet responses by 12 weeks of treatment, and all have sustained their responses (median follow up 10 months). Four patients exhibited improved hemoglobin levels 12 weeks after starting treatment (median hemoglobin increase of 2.1 g/dL) and two patients who were previously dependent on packed red blood cell transfusions have achieved transfusion-independence. Three neutropenic patients exhibited increased neutrophil counts after treatment with eltrombopag (median increase 0.46K cells/uL). These results provide evidence that eltrombopag can improve platelet counts in patients with severe refractory thrombocytopenia, and perhaps more surprisingly, have a clinically relevant impact on erythropoiesis and myelopoiesis. Updated data will be presented at the Society's meeting.

Disclosures:
Off Label Use: Eltrombopag for thrombocytopenia in refractory severe aplastic anemia patients.
Oxidative Stress in CML Stem and Progenitor Cells Correlates with Response to Imatinib
Authors: del Castillo Santiago , García Regina , Hernandez Agustin M , Campos Arturo , Entrena Laura , Llano Ma Paz Queipo De , Rosell Ana , Sanchez Guacimara , Ramirez Gemma 
Published: October 2019

Abstract
Abstract 4473

Introduction:
The BCR/ABL kinase alters the oxidative environment in chronic myelogenous leukemia (CML) cells, but the consequences of the increased reactive oxygen species (ROS) levels on signaling pathways remain unknown. Increased intracellular peroxides in progenitors cells have been linked to DNA damage, and promote self-mutation which subsequently render imatinib to resistance and failure to eliminate all leukemia cells.

Material and Method:
A total of 8 patients and 3 health controls were included in this study. 1 patient only at diagnosis, 3 patients at diagnosis and 3 months after treatment with Imatinib, 1 case after 3 and 6 month with Imatinib, 2 cases are long follow-up resistant patients and 1 with long follow-up and good response. Oxidative stress biomarkers were studied by flow cytometry in the bone marrow progenitor cells.

Result:
Not only levels of BCR-ABR and the number of CML stem cells were lower with the treatment, the oxidative stress biomarkers were lower too in normal controls and in CML cells in patients with response to imatinib but in the resistant ones oxidative stress biomarkers were higher in all stem and progenitor cells.

Conclusion:
The levels of oxidative stress are significantly higher in CML cells than in healthy subjects and correlate with tumor burden as well as the response to imatinib. This data demonstrate a role of oxidative stress in restore normal hematopoiesis in CML patients and probably in imatinib resistance.

Disclosures:
García: Celgene: Research Funding.
A Disease Model to Predict the Long-Term Outcomes Associated with Treatments for Chronic Myelogenous Leukemia (CML).
Authors: Taylor Matthew , Lewis Lily , Patton Thomas , Hirji Ishan , Davis Catherine 
Published: October 2019

Abstract
Abstract 4480

Introduction
Dasatinib, a BCR-ABL inhibitor 325 fold more potent than imatinib, has been studied in DASISION a randomized comparison vs. imatinib in patients with newly diagnosed chronic phase CML. A computer simulation disease model was developed to examine long-term survival outcomes following treatment with dasatinib, imatinib, or nilotinib in this patient population.

Methods
A disease model was developed to estimate the lifetime health outcomes associated with each form of treatment. Five initial best-response categories were used (no response (NR), complete hematologic response (CHR), partial cytogenetic response (PCyR), complete cytogenetic response (CCyR) and molecular response (MR)), which were each linked to a disease prognosis based on previously published evidence. Mutually exclusive initial response rates for NR, CHR, PCyR, CCyR and MR came from the DASISION trial for dasatinib and imatinib while those for nilotinib were identified from published ENESTnd data. A quality of life (QoL) utility value was assigned to each health state (chronic phase with response, chronic phase without response, progressed, and dead), also from previous publications. Adverse events were accounted for in terms of their impact upon QoL utility values. Extrapolation beyond the published data was undertaken by calculating trend rates for the final three years of follow up and applying age related mortality rates. Uncertainty was incorporated into the analysis by fitting distributions to survival and using simulation techniques to run 1,000 iterations. The model calculated survival based on the mean number of years’ survival per patient, across the entire cohort. Adjusted QoL utility values were calculated by assigning a QoL utility value weight to each state (see above) and calculating the mean total outcome for the entire cohort. Incremental survival was calculated by comparing the mean survival associated with each treatment.

Results
The quality adjusted life years (QALYs) and life years (LYs) are given in Table 1. The QALYs and LYs were 12.238 and 14.727 for dasatinib, 11.506 and 13.822 for imatinib and 12.016 and 14.426 for nilotinib, respectively.

Conclusion
Based on simulation modeling, results suggest that treatment with dasatinib may be associated with long-term survival as well as QoL-adjusted survival benefits. Long-term follow-up of ongoing studies will be needed to confirm these predicted benefits.

Disclosures:
Taylor: Bristol Myers-Squibb: Consultancy. Lewis:Bristol Myers-Squibb: Consultancy. Patton:Bristol Myers-Squibb: Consultancy. Hirji:Bristol Myers-Squibb: Employment. Davis:Bristol Myers-Squibb: Employment.
The Use of Intravenous Antibiotics at the Onset of Neutropenia In Patients Receiving Hematopoietic Stem Cell Transplants: A Pre-Emptive Strategy.
Authors: Hamadah Abdulaziz 
Published: October 2019

Abstract
Abstract 4516

Background:
Hematopoietic Stem Cell Transplant (HSCT) recipients are at risk for fatal bacterial infections during the engraftment period. Empirical antibiotic(s) at the onset of febrile neutropenia remain the standard of care. HSCT recipients began receiving intravenous once daily ceftriaxone at the onset of neutropenia (neutrophils< 1.0) regardless of fever as part of The Ottawa Hospital Blood and Marrow Outpatient Programme policy from Jan 2009; “pre-emptive” approach. We examined the impact of this policy on HSCT recipient outcomes.

Methods:
A retrospective “before-after” study was conducted to compare 2 cohorts [Jan 2008 - Dec 2008 (Empiric strategy) vs. Jan 09 - Dec 2009 (Pre-emptive strategy)] of patients receiving HSCT. Baseline characteristics between the groups were compared with 2 sample tests. Categorical variables and continuous variables were compared using Chi-squared and Wilcoxan rank-sum tests respectively.

Results:
There were 238 HSCTs performed between Jan 2008 and Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Baseline characteristics between the cohorts were similar. Infection related mortality at 100 days after HSCT and during the engraftment period was similar with a pre-emptive strategy compared to an empiric strategy (7.2% vs 10.2%; p=0.41 and 3.6% vs 7.1%; p=0.24) respectively. Further, there were no differences in ICU admissions or length of hospital stay. Both microbiologically (MDI) and clinically documented infections (CDI) were reduced (11.7% vs 29.1%; p=0.001 and 18.2% vs33.9%; p=0.007) with the pre-emptive strategy compared with an empiric strategy. Importantly, recipients of autologous HSCT appear to have a lower infection related mortality and reduced infection related ICU admissions during the engraftment period with the pre-emptive strategy compared to an empiric strategy (0% vs 6.8%; p=0.03 and 2.9% vs 12.2% p= 0.04). The need for escalation of antimicrobial treatments, resistance pattern of MDIs and cost of antimicrobial treatment were not different between the two groups.

Conclusion:
The use of once daily intravenous ceftriaxone at the onset of neutropenia in patients receiving HSCT is safe and effective particularly in patients receiving autologous HSCT. Further studies are warranted to study the impact of this “pre-emptive” strategy.

Disclosures:
No relevant conflicts of interest to declare.
Application of Mesenchymal Stem Cells Derived From the Umbilical Cord Instead of Bone Marrow In Hematopoietic Stem Cells Transplantation.
Authors: Peng Ching-Tien 
Published: October 2019

Abstract
Abstract 4544
Bone marrow-derived mesenchymal stem cells (BMMSCs) have been found to enhance engraftment of hematopoietic stem cell transplantation (HSCT), plus show effect against graft-versus host disease (GVHD) because of their immunosuppressive properties. However, harvesting these cells is an invasive and painful procedure. To substitute BMMSCs from alternative sources is necessary. We intravenously infused ex vivo-expanded third-party umbilical cord-derived mesenchymal stem cells (UCMSCs) obtained from a bank 8 times in 3 patients who developed severe, steroid-resistant acute GVHD after allogeneic HSCT. The acute GVHD improved with each infusion of UCMSCs. Besides, after cotransplantation of cord blood and UCMSCs in 5 patients, we found UCMSCs enhanced absolute neutrophil counts and platelet counts recovery. No adverse effects after UCMSCs infusions were noted. We also found that UCMSCs had superior proliferative potential and greater immunosuppressive effects than BMMSCs in vitro. This is the first report of UCMSCs in human clinical application. These findings suggest UCMSCs are effective in treating aGVHD and can enhance hematopoiesis after HSCT. Considering that they are not only easy to obtain but also proliferate rapidly, UCMSCs would be the ideal candidate for cell-based therapy, especially for diseases associated with immune responses because of their immunosuppressive effects.

Disclosures:
No relevant conflicts of interest to declare.