bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological and Cytogenetic Comparison of Patients with Acute T Lymphoblastic Leukemia and Lymphoblastic Lymphoma
Authors: Raza Sania , Patnaik Mrinal M. , Feldman Andrew L , Ansell Stephen M. 
Published: October 2019

Abstract
Abstract 2705

Background:
Due to similar cytomorphological features and treatment strategies, T lineage lymphomas (T-LBL) and lymphoblastic leukemias (T-ALL) are usually grouped together as a single entity. Traditionally, the difference between T-LBL and T-ALL has been based on percentage of blasts found in the bone marrow (BM): >25% BM blasts and/or presence of peripheral blood (PB) blasts consistent with T-ALL. Recent studies, based on immunophenotypic, cytogenetic and molecular differences, emphasize the clinical uniqueness between T-LBL and T-ALL and argue against grouping them as a single entity.

Objectives:
To perform a clinicopathologic and cytogenetic comparison between patients with T-LBL and T-ALL in order to identify differences between these disease groups.

Methods:
We utilized the Mayo Clinic Lymphoma database to identify consecutive adult patients (>18 years) diagnosed with T-cell leukemia and lymphoma from 1980 to 2010. The patients were sub-divided into T-LBL and T-ALL based on BM and PB blasts (absence of BM and PB blasts consistent with T-LBL). Clinicopathological and cytogenetic characteristics were retrospectively reviewed.

Result:
50 patients met the criteria for T-cell leukemia/lymphoma (29-T-ALL, 21-T-LBL). 50% of patients in each group were females with median age at diagnosis of 32 years for T-LBL and 29 years for T-ALL. Characteristics associated with a statistically significant survival difference for the cohort included: white blood cell count at diagnosis (>100,000/cmm), platelet count (<50,000/cmm), LDH (>500 U/L), presence of BM blasts and an adverse karyotype (hypodiploidy and MLL rearrangements). ECOG performance status, number of lymph node groups involved, extranodal disease, CNS involvement and constitutional symptoms had no impact on survival. Furthermore, no overall survival difference between patients with T-LBL and T-ALL was identified (figure 1).
Among patients with T-LBL, 11 (51%) patients with extranodal disease had shortened survival (p=0.02). CNS involvement was seen in 4 (19%) of T-LBL patients and 5 (17%) of T-ALL patients, and did not affect overall survival (p=0.8). 4 (19%) T-LBL patients and 1 (3%) T-ALL patient had pleural involvement at diagnosis. There were no morphologic, flow cytometric, or immunohistochemical differences noted between the two groups.

Conclusion:
In a large study from a single institution, we confirm no survival difference between T-LBL and T-ALL, which further provides ongoing support that from a therapeutic standpoint these groups can be viewed as a single entity. However, we hope to further clarify clinical differences by performing microarray and chemokine analysis on available tissue specimens.

Disclosures:
No relevant conflicts of interest to declare.
Long-Term Experience with Allogeneic Bone Marrow Transplant (BMT) in Chronic Myeloid Leukemia
Authors: Enrico Alicia Inés , Basquiera Ana , Napal Juan Jose , Sturich Ana Gabriela , Prates Maria Virginia , Garcia Juan , Yantorno Sebastian , Milone Santiago , Navickas Alicia , Milone Jorge 
Published: October 2019

Abstract
Abstract 4582

Introduction:
Introduction of imatinib mesylate has changed the approach towards bone marrow transplantation in Chronic Myeloid Leukemia (CML). Historically considered as a curative therapeutic option, with a probability of disease free survival ranging from 40 to 60%. Its indicated use has been restricted to patients with treatment failure to prior tyrosin-kinase inhibitors or blast crisis.

Objective:
To assess the outcome of patients with CML who undergo BMT

Materials and methods:
66 patients who underwent allogeneic BMT between the years 1994 and 2011 in two health care facilities were analyzed. 63 (93%) were performed between 1994 and 2005. At the time of transplantation, patient status was: 56 patients in 1st Chronic Phase and 10 in advanced phases. Fourteen patients received Unrelated Donor BMT and 37 had Related Donor BMT. Transplant risk was assessed, based on the European Bone Marrow Transplantation (EBMT) score (sc). The conditioning regimens which were used included: for patients in chronic phase, cyclophosphamide (Cy) and busulfan (Bu) and for patients in accelerated phase etoposide (VP 16) was added to the previous regimen, and for unrelated donors BuCy + ATG or alentuzumab was used. Prophylaxis for Graft vs Host Disease (GVHD) was performed with a two-drug regimen (cyclosporine, methotrexate), with or without methylprednisone.

Result:
66 patients were recorded (28 female/38 male), with a mean age of 35 years at the time of transplantation (range 8–55). The source of Stem Cell was bone marrow in 60 patients and peripheral blood in 6 patients. 43% of patients developed GVHD: (29 patients) according to clinical criteria established by the European Cooperative Group. Overall Survival (OS) was 50% with a mean follow-up of 48 months. Analyzed according to the EBMT risk score, OS was 64% in the 0–2 score group and 31% in patients with a 3–5 score. Procedure-related mortality was 16%, and the most frequent causes included: hepatic veno-occlusive disease, infections, GVHD, and graft failure.

Conclusions:
BMT in patients with CML has been substantially reduced since the introduction of tyrosin-kinase inhibitors. In our experience, this shows its healing potential with an extended follow-up and a prolonged survival.

Disclosures:
No relevant conflicts of interest to declare.
Polymorphisms of Mir-34b/c, Mir-146a and Mir-196a-2 and Predisposition to Chronic Lymphocytic Leukemia and Monoclonal B-Cell Lymphocytosis
Authors: Jamroziak Krzysztof , Szemraj Janusz , Rawstron Andy , Szemraj-Rogucka Zofia , Grzybowska-Izydorczyk Olga , Giannopoulos Krzysztof , Buda Gabriele , Martino Alessandro , Jesionek-Kupnicka Dorota , Franiak-Pietryga Ida , Piotrowska Magdalena , Robak Tadeusz 
Published: October 2019

Abstract
Abstract 4585
Since microRNAs control expression of protein-coding oncogenes and tumor suppressor genes, functional microRNAs single nucleotide polymorphisms (SNPs) may modulate the risk of tumorigenesis including susceptibility to chronic lymphocytic leukemia (CLL). In this case-control study we investigated whether pri-miR-34b/c rs4938723 (T-to-C), miR-196a2 rs11614913 (C-to-T) and miR-146a rs2910164 (G-to-C) SNPs influence predisposition to CLL or monoclonal B-cell lymphocytosis (MBL). miR-34 family members are direct transcriptional targets of tumor suppressor p53, and miR-34b/miR-34c have been recently proposed as regulators of TCL1 (T-cell leukaemia/lymphoma 1) expression in CLL. A rs4938723 SNP in the promoter region of pri-miR-34b/c might affect transcription factor GATA binding and pri-miR-34b/c expression. Alterations in miR-196a2 and miR-196a2 may represent common cancer predisposition pathways as miR-196a2 rs11614913 and miR-146a rs2910164 have been recently associated with altered risk of different solid tumors including breast, lung, prostate and liver cancers. Additionally, we verified the impact of these microRNA SNPs on prognostic factors and clinical course of CLL. Genotyping was performed using PCR-based assays in a total of 561 Caucasians including 195 patients with CLL, 166 patients with MBL and 200 healthy control individuals. The assessed minor allele frequencies (MAFs) of the investigated SNPs were as follows: for rs4938723 SNP C allele frequency was 0.37 in CLL, 0.36 in MBL and 0.30 in controls, for rs11614913 SNP T allele frequency reached 0.43 in CLL, 0.42 in MBL and 0.39 in controls, and for rs2910164 SNP C allele frequency was 0.29 in CLL, 0.30 in MBL and 0.26 in controls. Logistic regression analysis did not detect significant associations of CLL or MBL with studied genotypes or alleles (p>0.05). Moreover, none of the tested genetic variants was found to influence CLL patients’ progression-free survival (PFS) or overall survival (OS) with median follow-up time from diagnosis of 3.0 (0–13.9) years. In conclusion, our data suggest that investigated SNPs in pri-miR-34b/c, miR-146a and miR-196a-2 genes are not likely to play a major role in the susceptibility to CLL and MBL or in clinical outcome of CLL.

Disclosures:
No relevant conflicts of interest to declare.
FLT3 Internal Tandem Duplication and Kinase Domain Mutations Remain Poor Prognostic Markers in Intermediate Cytogenetic AML After Treatment with Transplant in First Remission
Authors: Aljurf Mahmoud , Abalkhail Hala , Almhareb Fahed , Chaudhri Naeem A. , Walter Claudia Ulrike , Toulimat Mohammed , Al Zahrani Hazzaa , Khalil Salem , Mohamed Said , Rasheed Walid , Alsharif Fahad , Albitar Maher 
Published: October 2019

Abstract
Abstract 4627
The internal tandem duplication (ITD) and tyrosin kinase domain (TKD) D835 mutation in the Fms-like tyrosine kinase receptor-3 gene (FLT3) are perhaps the most studied prognostic molecular markers in acute myeloid leukemia (AML). However most of the studies have been in patients treated with standard intensive chemotherapy. The prognostic significance of FLT3, especially the TKD D835, in AML patients treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT) is not well studied.We studied the prognostic value of both FLT3-ITD and FLT3-D535 mutations in patients with AML treated with HSCT.

Methods:
Samples from 87 patients with AML were analyzed for FLT3 ITD and D835 mutations using fragment length analysis for ITD and restriction enzyme digestion followed by fragment length analysis for D835. All patients were diagnosed with AML, treated with intensive chemotherapy, then HSCT. They included 66 (76%) patients with intermediate cytogenetic abnormalities and 21 (24%) patients with adverse cytogenetics.

Results:
ITD mutation was detected in 18 patients (21%) patients, while the D835 mutation detected in 6 patients (7%). FLT3-ITD was associated with significantly shorter overall survival (OS) when all patients are considered (P=0.006). When only patients with intermediate cytogenetic abnormalities treated with HSCT in their first complete response (CR1) are considered, FLT3-ITD was significantly associated with poor OS (P=0.001). Event free survival (EFS) was also significantly shorter in patients with the FLT3-ITD (P=0.005). Similarly, D835 mutation was associated with significantly shorter OS (P=0.002) in this group of patients. Surprisingly, in patients with poor cytogenetic abnormalities, patients with FLT3-ITD had significantly longer survival (P=0.05), although the number is too small.

Conclusion:
Our data suggests that FLT3 mutations, both ITD and D835, remain poor prognostic markers in patients with AML treated with intensive chemotherapy followed by HSCT, but only in patients with intermediate risk cytogenetic abnormalities and this may not be relevant in patients with high-risk AML.

Disclosures:
No relevant conflicts of interest to declare.
4Ts HIT Scoring in the Medical-Surgical ICU
Authors: Crowther Mark A. , Heels-Ansdell Diane , Williamson David , Granton John , Burry Lisa , Lamontagne Francois , Finfer Simon , McDonald Ellen , Vallance Shirley , Klinger James , Friedrich Jan , Paunovic Bojan , Walter Stephen , Zytaruk Nicole , Cook Deborah J , Warkentin Theodore E. 
Published: October 2019

Abstract
Abstract 4669

Background:
Thrombocytopenia occurs in 20–45% of critically-ill medical-surgical patients. The ‘4Ts’ HIT score (with 4 domains: Thrombocytopenia, Timing of thrombocytopenia, Thrombosis and oTher reason for thrombocytopenia) might reliably identify patients at low risk of HIT. Agreement on 4Ts scoring is uncertain in this setting.

Objective:
To compare 4Ts HIT scores among research coordinators (who scored real-time), and 2 adjudicators (who scored retrospectively, independently) during an international heparin thromboprophylaxis trial.

Methods:
763 of 3746 medical-surgical ICU patients in PROTECT met enrolment criteria in this HIT substudy, if any of the following occurred: platelets <50×109/L, platelets decreased to 50% of ICU admission value, venous thrombosis, or if HIT was otherwise clinically suspected. Persons independently completed 4Ts scores blinded to all laboratory HIT results and each others' scores. 475 of these patients had a central or local laboratory HIT test performed and had 4Ts scoring by adjudicators; 432 were scored by research coordinators.

Results:
Most patients (410, 86.3%) had a 4Ts score ≤3 conferring a low pretest probability (PTP) of HIT whereas 57 (12.0%) had a moderate PTP, and 8 (1.7%) had a high PTP, as determined by adjudicator consensus. Raw agreement on the 4Ts score was good for central adjudicators overall; however, agreement between adjudicated consensus scores and real time research coordinator scores was not as high. 4Ts agreement (raw and chance-corrected) is presented below.

Conclusions:
Real time 4Ts scoring by research coordinators was reasonably close to that obtained by calibrated central adjudicators, suggesting the 4Ts score is somewhat reliable at the bedside when performed by trained personnel. The fourth domain of 4Ts (oTher causes of thrombocytopenia) generated the most disagreement. Further studies of 4Ts scoring by bedside clinicians is needed.

Funding:
Heart and Stroke Foundation of Canada

Disclosures:
Crowther: Pfizer: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; BI: Honoraria; CSL Behring: Consultancy; Octaphram: Consultancy; Artisan: Consultancy. Off Label Use: Dalterparin is not indicated for prolonged prophylaxis in critically ill medical patients. Zytaruk:Pfizer: donated study drug dalteparin for PROTECT. Cook:Pfizer: donated study drug dalteparin for PROTECT. Warkentin:Sanofi-Aventis: Speakers Bureau; Pfizer Canada: Speakers Bureau; GlaxoSmithKline: Consultancy, Research Funding; GTI Diagnostics: Consultancy, Research Funding; Canyon Pharma: Consultancy, Speakers Bureau; Informa: Patents & Royalties.
Heparin-Induced Thrombocytopenia Antibody Is More Common in Patients with Active Bacterial Infections
Authors: Smith Melody , Patel Prapti A. , Dowell Jonathan E , Frenkel Eugene P. , Sarode Ravindra , Shen Yu-Min P 
Published: October 2019

Abstract
Abstract 4678
Heparin mobilizes and binds to platelet factor 4 (PF4), forming a heparin-PF4 complex on the platelet surface. Rarely, IgG antibodies recognize and bind to the immune complex, causing platelet activation and thrombin generation, resulting in heparin induced thrombocytopenia (HIT). There is evidence that PF4 has a role in antibacterial host defense and can concurrently prime the immune system with IgG antibodies that can cross-react with the heparin-PF4 complex (Krauel et al, Blood 2011). In the setting of a bacterial infection, the PF4 molecules interact with the bacterial cell wall and induce antibody production. These antibodies are able to recognize any bacteria coated in PF4, resulting in phagocytosis. In the setting of heparin, this antibody can cross react with the heparin-PF4 complex and result in HIT. In vitro studies suggest that E. coli, S. pneumo, and S. aureus coated in PF4 cross-react with human heparin induced anti-PF4/heparin antibodies.
We have collected a database of patients being tested for HIT at our institution and performed a retrospective analysis of the incidence of bacterial infections. We hypothesize that patients who have a bacterial infection will be more likely to develop HIT due to anti-bacterial antibodies that cross-react with the heparin-PF4 complex. We collected culture data from 54 patients with positive HIT antibody by ELISA and 178 patients with negative HIT antibody. The incidence of positive cultures and active infections in described in table 1. In the HIT negative patients, 61/178 (34.3%) had positive cultures, compared to 28/54 (51.9%) in the HIT positive patients (p=0.0198). Given that there is data to support E. coli, S. pneumo, and S. aureus-induced antibody cross-reactivity, we performed a subgroup analysis of the incidence of these specific bacterial infection in HIT positive and negative patients (33.3% versus 19.7%, p=0.0357). There is a statistically significant difference noted in the active infections, subgroup analysis, as well presence of any positive cultures in the HIT positive patients as compared to the HIT negative patients.Table 1Colonized Infections (%)Active Infections (%)E. coli, S. pneumo, S. aureus (%)Any + culture (%)HIT negative (n=178)15 (8.4)61 (34.3)35 (19.7)66 (37.1)HIT positive (n=54)2 (3.7)28 (51.9)18 (33.3)29 (53.7)p value0.2420.01980.03570.0293
This data supports that in the setting of active infection, particularly with E. coli, S. pneumo, and S. aureus, HIT antibody results should be carefully evaluated. Patients with positive cultures are likely to have thrombocytopenia from infection or sepsis, regardless of the presence of a HIT antibody. Thus, additional factors, such as the patient's 4T score and the presence of thrombosis should be considered prior to initiating treatment for HIT.

Disclosures:
No relevant conflicts of interest to declare.
Initial Management of Suspected Heparin-Induced Thrombocytopenia: Opportunities for Education
Authors: Smith Melody , Dowell Jonathan E , Frenkel Eugene P. , Sarode Ravindra , Shen Yu-Min P 
Published: October 2019

Abstract
Abstract 4686
According to the current recommendations for patients being evaluated for heparin-induced thrombocytopenia (HIT), a pretest assessment for the probability of HIT should be performed to evaluate the need for laboratory testing and the treatment modality that the patient should receive. The 4T score is an accepted clinical tool used for this purpose. For patients with a 4T score <4 discontinuation of heparin products is not indicated. However, in those patients who have a 4T ≥4, heparin should be discontinued and treatment with a direct thrombin inhibitor (DTI) should be initiated while performing the immunologic assay for HIT antibody.
In this study, a database of patients being tested for HIT at our institution was compiled and retrospective analysis was performed to determine whether our treatment population was being managed appropriately. The treatment of 159 patients in whom HIT antibody had been sent over a 2- year period, from 5/2008 to 5/2010, was assessed. Of the sample population, 32/159 (20%) had not been exposed to heparin prior to the HIT antibody being sent. Furthermore, the majority of the patients, 104/159 (65%) had a 4T score <4. Thus fully 85% of the patients tested in this cohort did not need to be tested. Of the latter group with heparin exposure but low clinical probability for HIT, 57/104 (54%) had heparin unnecessarily discontinued once HIT was suspected.
Most notably, 23/159 (14%) of the patients had a 4T greater than 4. The data for these patients indicates that the majority of them were not treated as per the current guidelines. As noted in the Table, 69% of these patients had either no treatment, meaning that heparin was not discontinued, or simply had heparin stopped with no DTI initiated. Only 5/23 (22%) of the patients in this cohort were placed on a DTI. Of these patients, 2 were also placed on warfarin, as they were noted to have active thromboses.
This data suggests that the management of patients suspected of having HIT at our institution is not consistent with the current recommendations with wasteful practices and inappropriate therapy. These results highlight opportunities for further education of clinicians regarding HIT.No treatmentHeparin stopped onlyDTIWarfarinNot exposed to heparin (n=32)324T less than 4 (n=104)4757004T greater than 4 (n=23)41452

Disclosures:
No relevant conflicts of interest to declare.
Rituximab May Be a Useful Option in Children with Severe Chronic Immunthrombocytopenia (ITP)
Authors: Halimeh Susan , Schubert Erdmuth , Paulus George , Rott Hannelore , Schaefers Michael , Quabeck Klaus 
Published: October 2019

Abstract
Abstract 4692
This otherwise healthy 12-year-old girl presented in March, 2011 with a history of severe ITP that had been diagnosed in November, 2007. Since then, she had suffered from recurrent bruises, petechiae, epistaxis, persistent bleending after tooth-loss and during menstruation (menarche: April, 2010), and subsequent iron-deficiency. Severe headache of sudden onset turned out to be caused by intracranial hemorrhage (ICH) in December, 2009, and in September, 2010, respectively. CT-scans in September 2010 revealed 2 additional ICH which had occured without symptomps. Fortunately, she recovered without sequelae from these complications. The initial and the subsequent treatment consisted of immunoglobulie (IG) and prednisone (IV or orally) given in various doses and for various time-intervals, always followed by a rise in platelet count for short periods of time, and a subsequent decline, when the drugs were withdrawn. Both ICH occured in phases of watchful waiting, while platelet count were below 1000. Splenectomy was offered and repeatedly denied by the patient and her parents.
After the second ICH (Sept 2010) the patient received continuous weekly IG as prophylaxis of further ICH. Serious side-effects of prednisone in this patient (Cushing’s habitus, abdominal striae, insomnia and secondary depression) led to withdrawal of this drug. Since February 2011, the efficacy of IG was decreasing significantly, and the patient was referred to hematological practice for further treatment. We obtained the patient’s and her parents’ informed consent for a trial of 4 weekly doses rituximab (375mg/ square meter body surface after premedication with an antihistamine and 50mg prednisone). The infusions were given over a time-period of 5 weeks (May – June 2011) and were well tolerated. Platelet counts began to rise significantly after the 2. course and have remained above 200 000 since the beginning of July, 2011 without any other medication.
Through the long-term course in this patient yet has to be followed, we feel that Rituximab (though not licensed for ITP in Germany) has been a useful option in this heavily pretreated patient. Because of good clinical results from US trials, like cases confirm previous reports of B.U. Mueller and C.M. Benett (Pediatr. Blood Cancer 2009; 52:259 and Blood 2006; 107:2639) we are now able to perform this treatment.

Disclosures:
No relevant conflicts of interest to declare.