bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imatinib Mesylate and Hyper-CVAD (IM-HCVAD) for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL).
Authors: Arellano Martha , Muringampurath-John Disni , Shenoy Pareen J. , Winton Elliott F. , Bryan Beverly , Langston Amelia , Sinha Rajni , McLemore Morgan L. , Heffner Leonard , Khoury H. Jean 
Published: October 2019

Abstract
Abstract 4103

Introduction
The addition of IM to hyper-CVAD led to higher rates and longer duration of complete remissions in Ph+ ALL. The purpose of this study is to report single institution experience with IM-HCVAD followed by maintenance IM or allogeneic transplantation in newly diagnosed adult Ph+ ALL treated between 10/02 and 08/08.

Methods
IRB-approved retrospective analysis of the institutional hematological database.

Results
Thirty-three patients, median age 51 (22-72), with 8 (24%) older than 60, presented with a median WBC of 24,000/mm3 (range, 2-200) and LDH of 2.6 ULN (1.3-11). Four (12%) had extra-medullary/CSF leukemia. Patients received a median of 7 (range, 1-8) cycles of IM-HCVAD followed by maintenance IM +/- POMP as tolerated (Blood 2004;103:4396-4407). After 2 cycles, 1 patient had primary refractory disease and expired, and 32 (97%) achieved complete hematological and cytogenetic remission. Twenty-four of 32 (75%) subsequently achieved complete molecular remission (CMR). Among those who achieved CMR, 6/24 relapsed with preceding loss of CMR in 4. Four of 8 who did not achieve CMR relapsed. One patient in CR was lost to follow-up after induction. Thirteen (39%) were allografted in CR1 using TBI-based myeloablative (9) or non-myeloablative (4) conditioning and 18 received maintenance IM-based therapy. With a median follow-up of 18.3 months (range, 4.4-76), 10 patients (32%) relapsed (1 post-transplant and 9 during IM maintenance) and received salvage therapy leading to CR2 in 4, of which 1 was successfully allografted, and 3 remain in CR2 with a follow-up of 20, 36, and 60 months. Eleven patients died (6 from GVHD/infection, and 5 from relapsed refractory leukemia). For the 13 allograft recipients in CR1 disease-free (DFS) and overall survival (OS) were 15, and 18 months; and 15 months and 20 months for the 18 IM maintenance patients, respectively (Figure). WBC > 30,000/mm3 and residual disease detected by flow cytometry after 2 cycles were associated with decreased OS (p < 0.03). A trend for lower survival was noted among African American patients (p= 0.07).

Conclusion
The addition of IM to hyper-CVAD is associated with high rates of CR (97%) in newly diagnosed Ph+ ALL. In this relatively small cohort with a short follow-up, peripheral blood PCR did not predict outcomes. Ph+ALL patients are candidates for novel maintenance regimens.

Disclosures:
Off Label Use: Imatinib combined with the hyper-CVAD chemotherapy. Khoury:Novartis Oncology: Honoraria.
Inhibition of Platelet Function by Aspirin in Insulin Dependent Diabetics without Vascular Disease.
Authors: Schwartz Kenneth A. , Schwartz Dianne E , Myneni Anjana , Nelson Peggy , Gossain Ved 
Published: October 2019

Abstract
Abstract 4172
Diseases like diabetes that are associated with increased platelet production are reported to have decrease aspirin (ASA) induced platelet inhibition. ASA inhibition of platelet function is mediated via acetylation of platelet cylooxygenase, which is completed approximately 30 minutes after ingestion. Thereafter production of new non-acetylated platelets increases the proportion of normal platelets gradually reversing ASA platelet inhibition. We tested the hypothesis that insulin dependent diabetics (type 1) without clinical evidence of occlusive vascular disease have less aspirin platelet inhibition than normal controls. The amount of ASA (325mg) platelet inhibition was measured using the slope (S) of platelet prostaglandin agonist (PPA) stimulated light aggregation curve that decreases after ASA. Aggregation was measured at 3 time points: before ASA ingestion, time 0 (T0); 2 hours post ASA (T2); and 24 hours after ASA (T24). Percent recovery from aspirin inhibition was calculated using the formula (T24–T2)/ (T0-T2) x100. Eight adult insulin dependent diabetic patients without clinical evidence of vascular disease and who were not taking aspirin were compared with 11 nondiabetic controls. 24 hours after aspirin ingestion diabetic patients recovered 10% of their maximal ASA platelet inhibition compared to 13% in controls (p=0.69). We conclude that recovery of platelet function from ASA in insulin dependent diabetics without clinical vascular disease occurs at the same rate as normal controls, suggesting that the previously reported decrease in platelet inhibition in diabetic patients may be related to increased platelet production associated with clinically evident occlusive vascular disease.

Disclosures:
No relevant conflicts of interest to declare.
Biological Activity of Low-Molecular-Weight Heparin Increases Over 9 Days in Patients Treated for Acute Venous Thromboembolism.
Authors: Harenberg Job , Bauer Kai , Abletshauser Claudia 
Published: October 2019

Abstract
Abstract 4176
Subcutaneous (s.c.) body-weight adjusted as well as fixed dose low-molecular-weight heparin (LMWH) for treatment of acute venous thromboembolism (VTE) has been proven to be at least as effective and safe as intravenous unfractionated heparin (UFH). We hypothesized that the anticoagulant effects of LMWH may accumulate during a 9 days fixed dose therapy in patients with acute VTE.
Ten patients received 8,000 IU LMWH certoparin bid s.c. for 9±1 days after having given written informed consent. The local ethics committee accepted the study protocol. Serial blood and urine were collected at days 2 and 9 and daily before and after the morning administration of the anticoagulant. The pharmacodynamic parameters were analysed on the anti-factor Xa S2222 method (aXa), heptest, thrombin generation inhibition assay (TGIA), and tissue factor pathway inhibitor activity (TFPI). The area under the activity time curves (AUC) of the parameters was compared at days 2 and 9.
LMWH reached steady state levels of the S2222 and heptest assay within 24 hrs. aXa, heptest, TGIA and TFPI were 22%, 38%, 13% and 22% higher at day 9 compared to day 2. The elimination half-lives of aXa and heptest and the aXa excreted into the urine did not differ between days 2 and 9, respectively. The AUC of the aXa did not correlate with the body weight of the patients.
Fixed dose, body weight-independent subcutaneous LMWH accumulated to some extend after 9 days of treatment in patients with acute VTE. However, the results of the clinical trials with the LMWH certoparin did not show more bleeding complications compared to UFH. Therapy with LMWH for more than 10 days may require dose reduction.

Disclosures:
Harenberg: Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Consultancy, Honoraria; Roche Diagnostics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bayer Health Care: Consultancy, Honoraria. Abletshauser:Novartis: Employment.
Survey On Directed Family Cord Blood Banking for Transplantation Among the National Cord Blood Bank Network in Italy.
Authors: Saracco Paola , Lombardini Letizia , Screnci Maria , Salvaneschi Laura , Tamburini Anna , Saccardi Riccardo , Pupella Simonetta , Pagliarino Mauro , Bargamaschi Paola , Urbani Serena , Fazio Luigina , Bosi Alberto , Grazzini Giuliano , Costa Alessandro Nanni 
Published: October 2019

Abstract
Abstract 4195
Directed family cord blood (DCB) storage provides hemopoietic stem cell source for transplantation (HSCT) for families with an existing or a potentially future recipient with HSCT curable disease (D). The National CB Banks Network in Italy (ITCBN) has a leading role in providing public DCB service for high-risk families, in compliance to GITMO directives for eligibility criteria (HSCT curable D: malignant MD, non MD, inherited ID). To provide best cost-effective practices recommendations it is important to report on DCB procedures and HSCT rate (HSCT-R) among public Banks. By 12.12.2008 almost 1800 DCB units were stored in 18 Italian Banks and 104 (9%) issued for HSCT. The present survey aims at summarizing the over 15 yrs DCB experience among 5 ITCBN Banks active since 1997 (range 1990-1997), and including 670 DCB units.

Results
Preliminary analysis reports a 94% overall compliance to eligibility criteria directives, and overall HSCT- R for an alive sibling of 12% (63/522); the 63 HSCT were 97% matched, for curing ID in 84% and with 72 % overall survival outcome. Different policies among Banks were compared (Bank vs others: 1) eligibility criteria distribution : Bank PV06 DCB for MD <50% (42% vs 55-67%), Banks Rm04,R04 significant DCB for non sibling recipient (parent with MD) (17-24% vs 0.5%-2%), Bank T02 with significant (53/261) DCB for future sibling with ID (20% vs 2-5%); 2) Timing of HLA typing: Banks T02,FI03,PV06 with DCB following prenatal HLA (20-27% vs 0%), Banks FI03,Rm04,PV06 with CB HLA typed at birth (61-73% vs 23-25%). Significant HSCT-R (37/177=21 %) was reported by PV06 (HLA selection based storage). Lowest HSCT-R by Rm04,R04 (3/101=3%-5/98=5%) (parental mismatch). At T02 when excluding DCB for future sibling (low birth rate), and autologous (11 ID) HSCT-R increased from 6% (15/261) to 9% (15/170)

Conclusion.
Advice for public long-term DCB storage should depend on HLA compatibility, potential recipient, disease progression, and likelihood/ timing of using DCB; Italian CB Banks are actively cohoperating to find best public banking practices to ensure a CDB storage system that is ethical, cost effective and responsive to patient needs.

Disclosures:
No relevant conflicts of interest to declare.
Measurement of Thrombin-Alpha-2-Macroglobulin Complexes Generated in Plasma.
Authors: Vetr Helga , Geiter Sabine , Graf Markus , Knapp Silvia , Binder Bernd R 
Published: October 2019

Abstract
Abstract 4205
The aim of this study is to evaluate a new assay (TECHNOZYM®TAM Activity) for measurement of thrombin-alpha2-macroglobulin (TAM) complexes. Furthermore, we asked the question whether the acute phase nature of a2Macroglobulin would be reflected in increased TAM levels in plasma of sepsis patients.
Thrombin generation was measured using TECHNOTHROMBIN®TGA which does not use any inhibitors of clot formation. Thus, clots formed during the reaction need to be removed either by centrifugation or filtration prior to sample transfer to the TAM assay which is a combined immuno-activity assay specifically detecting a2M bound thrombin.
Pre-existing TAM levels in various haemostatic samples did not differ significantly from those in normals, with one exception. Surprisingly, Factor X deficient samples expressed about 3 fold higher levels of TAM than normals. Approximately 4% of total thrombin generated was found in TAM complexes (TAM/AUC ratio 3,6 % ± 1, TAM concentration 73nM ±14). No significant difference in TAM values could be found for the different methods of clot removal (n=8; p>0,3). As expected, thrombin generation in normal as well as in factor deficient samples lead to approximately 10-fold increase of TAM. Only in FX-deficient and Coumadin samples no increase in TAM was observed. This is consistent with the small amount of total thrombin generated in these samples. TAM levels in plasma of sepsis patients were significantly higher (19.2nM ± 1.7) than in normals (9.7nM ±0.5; n=40, p<0,0001). Levels of TGA triggered TAM correlate with total amount of thrombin generated and TAM measurement in TGA samples is not necessary for routine TGA measurements. Furthermore, TAM levels are increased in the plasma of sepsis patients and do not correlate with acute phase markers in these patients. Thus TAM might be suitable as a new marker to differentiate a (sub)group of sepsis patients.

Disclosures:
Vetr: Technoclone GmbH: Employment. Geiter:Technoclone GmbH: Employment. Graf:Technoclone GmbH: Employment.
Cross-Reactivity of Rabbit Anti-Bovine Thrombin IgGs with Human α-Thrombin and a Recombinant Version of Human Thrombin (Recothrom™).
Authors: Zhu He , Hoppensteadt Debra , Wahi Rakesh , Paterson Craig , Fareed Jawed 
Published: October 2019

Abstract
Abstract 4211
It has been reported that patients exposed to topical bovine thrombin preparations may develop antibodies to bovine thrombin, factor V or various other proteins. In some cases these antibodies can cross-react with the corresponding human coagulation proteins. The present study was undertaken to determine if the antibodies induced by bovine thrombin antigens in rabbits could also cross-react with human a-thrombin and RecothromTM. Bovine crude thrombin and its purified versions, thrombin 4A and 4B, were administered to individual groups of rabbits on 0, 21, 42, 91, 123 and 151 days. Blood was drawn from each rabbit on days 30, 50, 105, 137 and 165, respectively. The antiserum from each rabbit and the pooled antisera from individual groups were purified to obtain the IgGs. Utilizing western blotting method, the possible cross-reactivity of each IgG with human thrombin and RecothromTM was explored using serial diluted human α-thrombin (20μg, 10μg, and 5μg) and RecothromTM (10U, 5U, and 2.5U). No cross-reactivity with either human α-thrombin or RecothromTM was observed with both anti-bovine crude thrombin IgGs and thrombin 4B IgGs collected on day 30 and day 165. However, anti-bovine thrombin 4A IgGs showed cross-reactivity with both human α-thrombin and RecothromTM. Cross-reactivity of anti-bovine thrombin 4A IgGs with human α-thrombin and RecothromTM was augmented with time. The minimum concentration of 4A IgG required to exhibit cross-reactivity with human α-thrombin and RecothromTM varied considerably among individual rabbits. These results demonstrate that rabbit anti-bovine thrombin 4A IgG could cross-react with both human a-thrombin and RecothromTM in a time/concentration-dependent manner.

Disclosures:
Paterson: King Pharmaceuticals: Employment.
Fludarabine Plus Cyclosporine for Refractory/Relapse Aplastic Anemia.
Authors: He Guangsheng , Wang Xiuli , Depei Wu , Sun Aining , Jin Zhengming , Qiu Huiying , Miao Miao 
Published: October 2019

Abstract
Abstract 4221

Objective
To evaluated the efficiency of fludarabine plus cyclosporine for refractory/ relapse aplastic anemia (AA).

Methods
We treated 7 refractory/ relapse aplastic anemia (AA) patients by fludarabine plus cyclosporine (fludarabine 25 mg/m2, day 1-5; cyclosporine 3mg/kg/d) from November 2003 to April 2008. The concentration of cyclosporine was maintained between 200-300ng/ml. The AA patients who was refractory to immunosuppressive therapy was defined as did not get transfusion dependence 6 months after treatment with ATG (anti-thymocyte globulin, ATG) and cyclosporine, who become transfusion dependent again after transfusion dependence were relapse.
In the patient group, 5 were males and 2 was female, with ages ranging from 12 to 45 years (median=22.5 years). 3 patients previously were treated by ATG plus cyclosporine, 3 were only received cyclosporine, and one was treated by Allo-HSCT (Table 1).

Results
The reponse rate was 57.1%(4/7), all were partial remission with count of neutrophil and levels of hemoglobin achieved normal levels while the number of platelet was lower than 100°Á109/L. No serious infection was found.

Conclusion
Fludarabine plus cyclosporine as a new immunosuppressive therapy for refractory/ relapse aplastic anemia patients is an effective regimen, it was worth to explore in clinical research.

Disclosures:
No relevant conflicts of interest to declare.
Apheresis of Hematopoietic Progenitor Cell (HPC) From Allogeneic Donors ≥60 Years of Age.
Authors: Janssen William E. , Rahn Darlene , Field Teresa , Kharfan-Dabaja Mohamed A , Ayala Ernesto , Ochoa Jose L , Hackett Martha , Anasetti Claudio , Fernandez Hugo F. 
Published: October 2019

Abstract
Abstract 4226
There has been reluctance to collect apheresis HPC grafts from donors of age 60 and beyond. This is predicated on concern over relative frailty, poor venous access, reduced potential for HPC mobilization, and reduced potential for stable engraftment of HPC transplant. We have expanded our transplant eligibility into patients beyond the age of 60, with the concomitant acceptance of matched sibling donors of similar age. We have reviewed 96 consecutive sibling donors, 19 of whom were of age ≥60 years at the time of collection. All donors were collected using Gambro Spectra apheresis instruments, and the volume of blood pheresed was gauged to target a CD34 dose of 5-10 million per Kg of recipient weight. We have found the following:
Age < 60 (n=77) Age ≥ 60 (n=19) p Blood volumes (Mean±Std) 4.9±3.3 6.1±3.1 .85 CD34/RecipKg E6 (Mean±Std) 8.1±2.8 5.8±1.7 .02 CD34/Blood vol E7. (Mean±Std) 18.0±11.7 10.9±7.8 .06 < 5E6 CD34/Kg Collected (n) 5 3 .21 > 1 collection (n) 12 7 .04 Catheter required (n) 23 6 .54 Grade 3+ pheresis complications 2 3 .47 ANC500 Median days (Min-Max) 16 (10-28) 16 (13-75) .14 Plt20K Median days (Min-Max) 16 (8-77) 16 (13-89) .30
These results suggest that donors of age ≥60 years may be successfully collected, and that the resultant grafts can be expected to produce successful transplants. There is not a higher toxicity rate or need for catheter insertion associated with the collections in the older age group. There is a clear trend, however, to reduced mobilization of CD34+ cells, as reflected in the need for more collections, and fewer CD34+ cells per blood volume leukopheresed. In spite of this, sufficient cells to produce functional grafts were collected from all donors, although a limited number of donors in both age categories failed to collect a full 5e+6 CD34/Kg. We conclude that in the context of an aging demographic, allograft donors of age ≥60 may be successfully employed for HPC collection. Further, we propose that the application of plerixafor in ≥60 year old donors should be investigated in the context of a growing need to collect allografts from donors in this age group.

Disclosures:
Off Label Use: sirolimus for graft-versus-host disease.
Characterization of the Putative Stem Cells From Umbilical Cord Blood.
Authors: Gaikwad Amos S. , Cubbage Michael , Goltsova Tatiana , Threeton Christopher , Ty Maria , Hollinger Alvin , Perlaky Laszlo , Hurwitz Mary 
Published: October 2019

Abstract
Abstract 4231
Cord blood (CB) is a rich source of hematopoietic stem cells (HSC) with long-term repopulating activity necessary for allogeneic stem cell transplantation. CD34+ stem cells are considered sufficient for transplantation, however recent progress in stem cell biology indicates that cells with other surface markers such as CD133 or cells expressing high aldehyde dehydrogenase activity with low side scatter (ALDHhigh/SSClow) or a rare side population (SP) of cells that exclude the Hoechst 33342 vital dye via multi drug transporters have been shown to possess stem cell properties. We characterized CD34+, CD133+, ALDH+ and SP in mononuclear cells (MNC) isolated from human CB. While the SP cell population is rare and detectable in few CB-MNC examined, we found abundant CD34+ and CD133+ cells (1.0+/-0.5 and 0.8+/-0.4 per 100 CD45+ MNC cells, respectively) following the ISHAGE protocol. A distinct ALDH+ cell population (median of 0.26%; range of 0.1 to 0.5%) was also present in all of the CB-MNC analyzed. Over 90% of the ALDH+ cells were also CD34+ and CD133+. The ability of CB-MNC to form colonies in methocult semi-solid media supplemented with cytokines yielded myeloid, lymphoid and erythroid colonies. The clonogenic potential of CB-MNC ranged from 16-48%. We are assessing the colony forming ability of purified stem cell fractions using flow cytometry. The clonogenic efficiency of these individual putative stem cells will be discussed.

Disclosures:
No relevant conflicts of interest to declare.
Chronic Myeloid Leukemia and BCR/ABL Signal Pathway Are Not Associated with AKT1 Pleckstrin Homology Domain(E17K) Mutations.
Authors: He Yanli , Zheng Jine , Hu Yanjie , Xiao Hong , Li Huiyu , Liu Jun , Li Xiaoqing , Du Wen , Chen Xiangjun , Hu Yu , Huang Shiang 
Published: October 2019

Abstract
Abstract 4262
AKT1 E17K mutation was recently found in several human cancers. PI3K/AKT is one of major downstream signal pathways of BCR-ABL oncogene and essential for CML leukemogenesis and IM resistance. More recently, it has been shown that increased PI3K/AKT activity in CML contributes to the development of drug resistance of malignant cells and combination of PI3K/AKT pathway inhibitor and rapamycin can efficiently kill imatinib-resistant BCR-ABL-expressing cells, highlighting the potential of PI3K/AKT as the new targets for CML therapy. Considering the central role of AKT in CML, we performed a screening study to investigate the possible role of AKT1 E17K mutation in CML in the Chinese population. To study the frequency of AKT1 E17K mutation in CML patients in Chinese population as well as its possible relation to IM sensitivity, we recruited 86 patients with CML revealed the presence of Philadelphia chromosome at diagnosis. At molecular level, B2a2, B3a2, B2a3 and B3a3 were identified by RT-PCR in 41,43,1 and 1 cases, respectively. Molecular response to IM was evaluated by real-time PCR at 6 months and 12 months after IM administration. The CCR, MMR and CMR were achieved in 74, 39 and 27 cases, respectively. No AKT1 E17K mutation was found in all patients. We also studied the AKT1 E17K genotype in 7 CML patients at blast stage. The additional genetic abnormalities were summarized. For these patients, CD34+ leukemic cells were purified by FACS from PBMNCs before DNA extraction. Again, we failed to detect any AKT1 E17K mutant in this group of patients.

Conclusion
No mutation was found in all patients with different phases, genotypes and IM responses. The results indicated that the acquisition of AKT1 E17K mutation should not be the major event in IM resistance or CML blasts.

Disclosures:
No relevant conflicts of interest to declare.