bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venous Thrombotic Events (VTEs) in Acute Myeloid Leukemia (AML) Patients During Induction Therapy (IT): Identifying Risk Factors, and Safety of Using Anticoagulation Therapy
Authors: Muslimani Alaa , Rifai Aya , Chisti Mohammad Muhsin , Ashkar Ayham , Muslemani Kinda , Margolis Jeffery , Nadeau Laura , Ye Hong , Micale Mark , Huang James , Jaiyesimi Ishmael 
Published: October 2019

Abstract
Abstract 3148

Background:
VTEs are common complications in association with IT which may cause additional morbidity and mortality in AML patients. However, treating patients with AML is challenging because of the cytopenias due to chemotherapy and the high risk for bleeding during IT. This study investigates frequency, risk factors, and safety of using anticoagulation (AC) therapy for VTEs during IT.

Method:
We retrospectively reviewed the charts of AML patients who received IT between January, 2000-January, 2011 at William Beaumont Health Systems. Exclusion criteria included a documented personal history of inherited thrombophilia. Data retrieved included the following: patient characteristics, leukemia subtype, cytogenetic risk, location of the VTEs, FLT3 mutations, IT regimen used (cytarabine and anthracycline regimens or hypomethylating agents), AC therapy, bleeding complications, mortality related to AC therapy. All patients who received AC were initially treated with regular intravenous unfractionated heparin or subcutaneous low molecular weight heparin. Patients were subsequently started on oral warfarin during the first 10 days of the initial treatment with a targeted INR of 2.0–3.0.

Results:
We found 48 of 363 (13.2%) AML patients developed VTEs during IT. Of those patients, 56.3 % were female. The VTEs occurred most frequently in upper extremities (58%) and were catheter-related. Other locations for VTEs included lower extremities (21%), pulmonary embolism (15%), and mesenteric or portal veins (6%). We note that 41 patients (87%) received AC therapy. Of these, three patients (7.3%) had bleeding complications and no AC therapy-related deaths were observed.
When the three cytogenetic risk groups were compared, there was no difference in the incidence of VTEs (good vs intermediate vs poor). Patients with FLT 3 mutations, however, had a significant higher incidence of VTEs when compared to patients without FLT3 mutations (55.3% vs 12% p <0.001). Finally, patients treated with cytarabine + anthracycline regimen had a higher incidence of VTEs compared to patients treated with hypomethylating agents (81.3% vs 4.2 % p <0.001.)

Conclusions:
We found that 13% of AML patients developed VTEs during IT, most commonly in upper extremities and were catheter-related. The risk for VTEs was markedly increased in patients with FLT3 mutations. Furthermore, using a cytarabine + anthracycline regimens carried a higher risk for VTEs when compared to regimens using a hypomethylating agents. Finally, using AC therapy during IT is relatively safe and is associated with low risk of bleeding complications.

Disclosures:
No relevant conflicts of interest to declare.
Absolute Lymphocyte Count As Predictor of Overall Survival for Patients with Multiple Myeloma Treated with Single Autologous Stem Cell Transplant: Experience of a Single Centre,
Authors: Jimenez-Zepeda Victor H , Reece Donna E. , Trudel Suzanne , Chen Christine , Franke Norman , Winter Andrew , Tiedemann Rodger E. , Kukreti Vishal 
Published: October 2019

Abstract
Abstract 4121
Post-Autologous stem cell transplant (ASCT) studies have demonstrated that early absolute lymphocyte count (ALC) recovery is associated with prolonged survival in some hematological malignancies. Peripheral blood lymphocytes from Multiple Myeloma (MM) were shown to have direct anti-MM activity by proliferative and cytotoxic responses to autologous and allogeneic myeloma plasma cells

Disclosures:
Jimenez-Zepeda: J & J: Honoraria. Reece:Bristol, Meyers, Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Merck: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium: Research Funding; Amgen: Honoraria. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.
A Retrospective Analysis of 344 Fludarabine Melphalan RIC Allogeneic Stem Cell Transplants for Myeloid and Lymphoid Malignancies In Australia and New Zealand 1998–2008,
Authors: Bryant Adam J , Pillai Elango , Kennedy Glen , Kalff Anna , Ritchie David , George Biju , Hertzberg Mark , Patil Sushrut S. , Spencer Andrew , Fay Keith , Cannell Paul , Berkahn Leanne , Doocey Richard , Spearling Ruth , Nivison-Smith Ian , Moore John 
Published: October 2019

Abstract
Abstract 4143

AIM:
Fludarabine Melphalan (FluMel) is the commonest Reduced Intensity Conditioning (RIC) regimen used in Australia and New Zealand. This study aims to assess the relative benefit of this regimen in both lymphoid and myeloid malignancies and to further delineate risk factors associated with an improved survival using RIC conditioning.

METHOD:
This was an ABMTRR based retrospective study assessing the outcome of FluMel RIC allografting in 9 Australian and New Zealand Centres between 1998 and 2008. Data was collected from centres using an excel based eCRF emailed to centres. Analysis was performed using Stata software and a p value less than 0.05 was considered significant.

RESULTS:
Median follow up was 3.4 years. There were 342 patients with a median age of 54 years (18–68) and 61% were male. 234 patients had myeloid malignancies with AML (n=166) being the commonest indication whereas there were 110 lymphoid patients with NHL (n=64) the main indication. TRM at D100 was 14% with no significant difference between the groups. OS and DFS were similar between myeloid and lymphoid patients (50% and 43% at 5 years respectively). There was no difference in the cumulative incidence of relapse and GVHD between the groups. Multivariate analysis revealed 4 adverse risk factors for DFS: non-HLA identical sibling donor, not in remission at transplant, previous autologous transplant, and recipient CMV +ve. The presence of Chronic GVHD was associated with a better DFS predominantly due to a marked reduction in relapse (HR 0.44, p=0.003).

CONCLUSION:
This is one of the largest analyses of Fludarabine Melphalan RIC transpants performed. This dataset confirms that FluMel provides durable remissions in both myeloid and lymphoid malignancies with 50% overall survival at 5 years. The multivariate analysis provides important clues for improving outcomes when planning FluMel conditioning in patients with haematological malignancies.

Disclosures:
No relevant conflicts of interest to declare.
Targeting CXCR4 with Cell-Penetrating Pepducins Enhances Survival in Disseminated Lymphoma
Authors: Covic Lidija , O’Callaghan Katie M , Ngyen Nga , Mo-Ying Hsieh , Klein Andreas K. , Sprague Kellie , Van Etten Richard A. , Kuliopulos Athan 
Published: October 2019

Abstract
Abstract 4244
The G-protein coupled receptor, CXCR4, which normally regulates interactions between stroma and hematopoietic stem cells in the bone marrow, is highly expressed on a variety of malignant hematological cells, such as lymphoma and lymphocytic leukemia cells. A new treatment concept has arisen that CXCR4 may be an effective therapeutic target as an adjunct to standard clinical treatments of hematologic malignancies. In this study we developed novel cell-penetrating lipopeptide antagonists of CXCR4, called pepducins, to interdict signaling to intracellular G-proteins in response to the CXCR4 ligand, SDF-1. We demonstrated that pepducins targeting the first (i1) or third (i3) intracellular loop of CXCR4 completely abrogated SDF-1-mediated chemotaxis of lymphocytic leukemia and lymphoma cell lines, as well as primary cells isolated from patients with chronic lymphocytic leukemia. Pepducins enhanced apoptotic cell death in lymphoma and primary leukemia cells when used in combination with the CD20-targeted antibody, rituximab. Furthermore, pepducin treatment significantly increased survival both as monotherapy and in combination with rituximab in mice with disseminated lymphoma. Together, these data demonstrate that CXCR4/SDF-1 signaling is effectively inhibited by cell-penetrating pepducins, suggesting that these lipopeptide antagonists may represent a potentially new treatment strategy for lymphoid malignancies.

Disclosures:
No relevant conflicts of interest to declare.
Azacitidine for the Treatment of Acute Erythroleukemia: Three Case Reports
Authors: Pierdomenico Francesca , Almeida Antonio 
Published: October 2019

Abstract
Abstract 4285
Acute erythroleukemia (AEL) is usually characterized by cytopenias with myelodysplastic features and is frequently associated with unfavourable karyotype. AEL is associated with a poor prognosis. There is no specific therapy for AEL and results of standard induction chemotherapy have been unsatisfactory. Hypomethylating agents have been used with success in myelodysplastic syndromes (MDS) with improved overall survival (OS) of MDS patients treated with azacitidine compared to those receiving conventional care regimens in the AZA001 phase III trial. Efficacy of hypomethylating agents has also been demonstrated in small groups of AEL patients, advocating a role for these agents alone, or in combination, as first line therapy. We report 3 patients diagnosed with AEL at a single institution treated with azacitidine 500 mg/m2 every 4 weeks divided in 5 days per cycle. All cases were diagnosed according to the 2008 WHO criteria and response criteria were based on the revised recommendation of the International Working Group published in 2003.Table 1.Patients demographic characteristics.PatientAgea (in years)SexCo-morbidities162MObesityBenign prostatic hyperplasia265MNone376MDiabetesTable 2.Patients hematological characteristics at baseline.PatientHemoglobin(g/dL)WBC(x109/L)/ANCPlatelets (x109/L)Cytogenetic18.01.700/0.47060000del(5)(q15q?(31)27.710.300/1.300367000Normal karyotype36.81.000/0.18012400045, XY, -7, del(20)(q11q13)Table 3.Treatment characteristics and response.PatientPrevious treatmentsTreatment durationTime to transfusion independencyBest Hematological responseTime to response1Conventional chemotherapy13 cycles4 cyclesComplete remission (no cytogenetic remission)6 cycles2None17 cycles5 cyclesComplete remission10 cycles3None9 cycles4 cyclesHematological improvement4 cycles
Therapy was well tolerated and all patients achieved transfusion independency with improvement in quality of life. At 12 months follow-up, all of them are alive, two patients are in complete sustained remission, one of whom awaits stem cell transplantation, while one patient is currently on supportive care.
These results confirm the active role of azacitidine in AEL.

Disclosures:
Almeida: Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau.
Use of All Trans Retnoic Acid (ATRA) Via Nasogastric Tube (NGT) in Patients Unable to Swallow in Treatment of Acute Promyelocytic Leukemia (APL): A Case Series
Authors: Preet Mohan , Sidhu Gurinder , Khillan Rajnish , Silbergleit Marc , Braverman Albert S. , Khillan Ratesh 
Published: October 2019

Abstract
Abstract 4300

Introduction:
ATRA is the critical component of treatment of APL, and when used in combination with anthracycline chemotherapy can induce remission in over 90% of patients. At initial presentation, patients are at high risk for bleeding or disseminated intravascular coagulation, which may be exacerbated by immediate chemotherapy. Except in patients with marked leukocytosis, ATRA should precede chemotherapy. ATRA is available as 10 mg capsules and should be ingested orally and not crushed. The capsules cannot, therefore, be used in patients unable to swallow, or administered by NGT.

Patients and Methods:
We present two APL cases where patients unable to swallow and acutely bleeding, received ATRA via NGT. ATRA capsules were opened, the free powder aspirated into a glass syringe, and the remaining capsule contents suspended in soy bean oil and aspirated into the same syringe (Shaw, 1995).

Case 1:
A 33-year-old female with juvenile onset diabetes and blindness presented with fever vaginal bleeding and coma with response only to painful stimuli. Her white blood count (WBC) was 0.5 k/MicroL with 27% bands, 20% lymphocytes and 10% promyelocytes; platelets were 18 K and PT/PTT was 14.7/33. Bone marrow (BM) was replaced by cells with granular cytoplasm and bilobed nuclei. PML-RARa was not detected by cytogenetics and fluorescent in situ hybridization (FISH), but was by PCR. Daunorubicin was administered and the ATRA oil suspension was given on 14 successive days. Hematologic recovery had occurred by day 16, PCR was negative for PML-RARa by 20, and following consolidation she remains in complete hematologic and cytogenetic remission after 7 months. MRI revealed white matter changes but after IV-HGG she regained consciousness.

Case 2:
A 66-year-old man with coronary artery disease presented with fever, rectal bleeding and pulmonary hemorrhage, which required intubation and mechanical ventilation. WBC was 7.9 with 3% bands, 19% lymphocytes and 22% promyelocytes. Platelet count was 13 and PT/PTT was 9.6/23.6. BM confirmed APL, with FISH positive for PML- RARa. He was started on ATRA oil suspension via NG tube and daunorubicin. By day 27 FISH was PML-RARa negative, but he continued to require ventilatory support for 3 weeks and succumbed to pneumonia and septic shock.

Conclusion:
In two patients unable to swallow and bleeding, ATRA administration as an oil suspension via NGT was safe and effective, inducing cytogenetic remission in both. IV liposomal ATRA is not FDA approved and no other parenteral formulation is available.

Disclosures:
No relevant conflicts of interest to declare.
Indications for Platelet Transfusions: How Educational Interventions Can Improve Compliance with National Guidelines
Authors: Katz Elena , Klek Malgorzata , Graham Robert E , Levine Randy L. 
Published: October 2019

Abstract
Abstract 4331

Intro:
Evidence-based guidelines are developed and promoted to help physicians implement best practice care. The American Society of Hematology (ASH) platelet transfusion guidelines changed in 2007 to a prophylactic transfusion threshold of 10, 000/μL from the previous 20,000/μL. We conducted a retrospective analysis at a metropolitan teaching hospital to assess how well physicians are complying with the new professional guidelines as well as the older, less stringent criteria to administer platelet transfusions. We then assessed the effect of an educational intervention on transfusion practices.

Methods:
All patients receiving platelet transfusions over a five-month period from Jan-Feb, and April-June 2010, admitted to the medical, critical care and cardiac services were reviewed. The medical record clinical indication was then evaluated against the ASH 2007 “Evidence-Based Platelet Transfusion Guidelines” (Slichter SJ. Hematology 2007): bleeding and platelets ≤50, 000/μL, pre-invasive procedure and platelets ≤50, 000/μL, prophylactic transfusion for platelets ≤10, 000/μL and WHO bleeding grade ≥ 2. We also assessed how the patients’ clinical indication met the previous prophylactic threshold for platelet transfusion of ≤20, 000/μL laid forth by the landmark study by Gaydos LA. et. al. (The quantitative relation between platelet count and hemorrhage in patients with acute leukemia. N Engl J Med 1962).
Following initial data collection, we implemented an educational intervention by giving a lecture, reviewing all indications for platelet transfusions, and distributing a pocket card to the house-staff on the medical wards in August, 2010. We subsequently gathered post-intervention data following the methods described above for four consecutive months from Sept-December, 2011.

Results:
Eighty-six patients on the selected units received a total of 241 platelet transfusions. Fifty nine percent of the time the patient's clinical indication failed to meet the currently accepted 2007 ASH guidelines and 37% of cases failed to meet even the older guideline.
Eighty-one patients received a total of 237 platelet transfusions post-intervention. Forty-seven percent of the time the patient's clinical indication failed to meet the currently accepted 2007 ASH guidelines and 19% of cases failed to meet the older guideline.

Conclusions:
Based on the significant difference observed between the pre- and post-educational intervention groups, our initial study shows that updating physicians on current evidence-based guidelines for platelet transfusions is a simple and effective means to improve transfusion practices. Periodic educational interventions may prove to even further enhance physician compliance with up-to-date guidelines and we plan to implement additional educational interventions throughout the upcoming academic year.

Disclosures:
No relevant conflicts of interest to declare.
Chronic Myeloid Leukemia Developing in a Patient with B-Cell Chronic Lymphocytic Leukemia – a Case Report
Authors: Zawilska Krystyna M , Malendowicz-Portala Lucyna 
Published: October 2019

Abstract
Abstract 4421
The coexistence of B-cell chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) in the same patient is rare. A 61-year-old man developed a lymphocytosis with morphologic and immunophenotypic feature of B-CLL (stage I according to the modified Rai classification), without indications for treatment. Ten months later he presented with a markedly elevated leukocytes count and splenomegaly. Myeloblasts, promyelocytes, myelocytes and metamyelocytes appeared in his peripheral blood. A bone marrow aspirate was hypercellular with an increased proportion of the myeloid series in all maturative stages; the percentage of lymphocytes was 3%. The immunophenotypic study demonstrated the typical feature of chronic phase of CML, simultaneously 2% of CD5+ CD19+ cells have been found. Unstimulated bone marrow culture shoved a 46,XY,t(9;22)(q34;q11.2) karyotype, and interphase FISH detected the presence of BCR/ABL fusion with 4,55×106 of p 210 and 1,55×103of p 190 copies/ml. Previously it has been shown that these two different hematological malignancies derive from distinct progenitors.

Disclosures:
No relevant conflicts of interest to declare.
Quantitative Assessment of WT1 Gene Transcript After Hematopoietic Stem Cell Transplantation Is a Powerful MRD Marker to Predict the Clinical Outcome in Acute Leukemia
Authors: Zhao Bingrui , Tang XiaoWen , Cen Jiannong , Jin Song , Shi Xiaolan , Wei Xiaoai , Chang Huirong , Sun Aining , Depei Wu 
Published: October 2019

Abstract
Abstract 4461

Background
WT1 is a panleukemic marker that is expressed in 90% of acute leukemias and has been used as MRD marker after chemotherapy or transplantation. However, the threshold of WT1 to predict relapse and outcome in acute leukemia (AL) patients post transplantation has not been well studied.

Objective
We evaluated the predictive value of quantitative Wilms’ tumor gene (WTl) assessment for relapse following hematopoietic stem cell transplantation (HSCT) in patients of AL.

Methods
The quantitative assessment of WT1 expression by real-time quantitative PCR (RQ-PCR) was measured in 63 AL patients (pts) with 326 bone marrow samples at the different time points post transplant. ROC (Receiver Operating Characteristic) curve was used to determine the WT1 threshold in order to predict clinical relapses. Furthermore, AL patients were divided into WT1 positive and negative groups according to the threshold of WT1, and the clinical outcomes of these patients post transplant were analysed retrospectively.

Results
BM samples from 19 pts who relapsed post transplanted showed significantly higher WT1 expression levels compared to the samples from 44 pts in remission (P<0.01), with a median expression level of 1270 (range 55–47596) and 132 (range 0–2959) copies WT1/104ABL, respectively. Ten of 18 relapsed patients died from recurrence, and had higher levels of WT1 expression than that of other 8 patients. Based on the ROC curve, the cut-off value of WT1 was 585 copies WT1/104ABL, dividing 63 patients into WT1-positive group (>585,n=21) and the negative group (≤585,n=42). The WT1-negative group had longer relapse- free survival (RFS) (P<0.01) and overall survival (OS) (P<0.01) than that of positive group.

Conclusion
Our data suggest that, in the HSCT setting, the sequential and quantitative analysis of WT1 may be useful as a leukemia marker for monitoring MRD, and predicting AL relapse post transplant.

Disclosures:
No relevant conflicts of interest to declare.
R-CHOP in the Treatment of EBV-Diffuse Large B-Cell Lymphoma of the Elderly
Authors: Beltran Brady E , Alva Jose C , Morales Domingo , Quinones Pilar , Castillo Jorge J 
Published: October 2019

Abstract
Abstract 4988

Introduction:
Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is a new entity considered in the most recent WHO classification. It is a very aggressive entity associated with a short survival. The role of rituximab-containing regimens in EBV+ DLBCL of the elderly is currently unknown.

Methods:
Between January 2002 and December 2010, 22 patients diagnosed with EBV+ DLBCL of the elderly were selected for this study, from which 11 patients received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and 11 patients received rituximab and CHOP (R-CHOP). Both groups received chemotherapy at every 3 weeks cycles. Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the immunohistochemical expression of bcl-6, CD10, CD30 and MUM-1/IRF4. Samples were also analyzed for the presence of EBV-encoded RNA (EBER) using an in situ hybridization (ISH) technique. Chi-square and Mann-Whitney tests were used to compare categorical and continuous variables, respectively. Overall survival (OS) estimates were calculated using the Kaplan-Meier method and compared using the log-rank test. P-values <0.05 were considered statistically significant.

Results:
The median age was 73 years (range: 49–85 years) with a male predominance (2.7:1). Eleven patients (50%) had advanced clinical stage (i.e. stage 3 and 4), nine patients (45%) had elevated LDH levels, eleven (50%) had performance status ECOG >1 and 13 (59%) had high or high-intermediate IPI scores. Fourteen out of 17 patients studied (82%) had a non-germinal center DLBCL. When comparing the CHOP and R-CHOP groups, there was no statistical difference in median age (p=0.87), sex distribution (p=0.63), stage distribution (p=0.28), IPI scores (p=0.15), Oyama scores (p=0.23), ECOG performance status (p=0.39), LDH levels (p=0.62), lymphocyte counts (p=0.06), hemoglobin levels (p=0.20), platelet counts (p=0.14), Ki67 expression by malignant cells (p=0.57) and proportion of patients with a non-germinal center profile (p=0.91). Additionally, there was no statistical difference in overall response and complete response rates (p=0.66). When evaluating median OS, patients treated with CHOP and R-CHOP had median OS at 5 and 20 months, respectively (p=0.04).

Conclusion:
Based on the results of this retrospective study, patients with EBV+ DLBCL of the elderly had a short OS when treated with CHOP alone; however, R-CHOP seems to confer a survival advantage in patients with EBV+ DLBCL of the elderly, although it seems shorter than in EBV-negative DLBCL patients.

Disclosures:
Castillo: GlaxoSmithKline: Research Funding; Millennium Pharmaceuticals: Research Funding.