bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competition In Engraftment of Normal Hematopoietic Stem Cells and Leukemic Stem Cells
Authors: Park Gyeongsin , Heuser Michael , Berg Tobias , Humphries R. Keith 
Published: October 2019

Abstract
Abstract 4836
Engraftment is a process including homing to bone marrow, implantation and proliferation. Implantation implies interactions with specialized microenvironments, niches, in which hematopoietic stem cells (HSCs) live and are regulated. Studies have demonstrated the possibility that leukemic stem cells (LSCs) interact with niches in a similar manner to HSCs. We investigated whether HSCs and LSCs compete with each other in their engraftment. We employed a mouse transplantation assay with unmanipulatated bone marrow cells (BMCs) as a source of normal HSCs and LSCs generated by transduction of BMCs with Meningioma 1 (MN1), a potent oncogene causing myeloid leukemia in mice. In irradiated recipients (750 cGy), cotransplantation of leukemic cells (1×105) with various numbers of BMCs (1×105, 1×106 and 1×107) demonstrated that the engraftment level of leukemic cells is influenced by BMCs in a dose dependant manner (5.2%, 41.3% and 82.2% at 2-weeks; 52.3%, 69.5% and 86.9% at 4weeks; mice died before the 5 weeks bleeding, 94.9% and 97.5% at 5weeks, respectively). Cotransplantation of various numbers of leukemic cells (1×104, 1×105 and 1×106) with a fixed number of BMCs (1×106) demonstrated a similar pattern of leukemic engraftment (7.0%, 59.5% and 87.1% at 2weeks; 62.0%, 85.7% at 4 weeks, and mice died before the four week bleeding, respectively). To further elucidate the competition between HSCs and LSCs, we transplanted the cells at different time intervals. Transplantation of normal BMCs (1×106) 2 days prior to transplantation of LSCs (1×105) resulted in much reduced levels of leukemic engraftment compared to that seen in mice simultaneously transplanted (3.5% vs 59.5% at 2 weeks; 73.1% vs 85.76% at 4weeks). This competitive suppression of leukemic engraftment was further enhanced by transplanting larger numbers of normal BMCs (2×107) as little as 12 hours prior LSC transplantation (5×105) compared to simultaneous injection (0% vs 7.26% at 2weeks, 0.9% vs 35.3% at 3 weeks, and 6.0% vs 60.6% at 4 weeks). When BMCs (1×105) or leukemic cells (1×105) were transplanted at equal doses of 1×105 together with normal helper cells (1×106) the leukemic cells expanded 280-fold compared to only 7.3 fold for normal BMCs at 2 weeks (total cell count from two femurs and two tibias per 1×105 transplanted cells). Thus the competitive suppression of leukemic cell growth seen upon sequential transplantation of normal BMCs is not readily explained by enhanced kinetics of normal BMC growth but rather by competition at the level of initial engraftment.
In conclusion, our data demonstrate that there is a competition between normal and leukemic cells during the engraftment process, suggesting niche competition of HSCs and LSCs.

Disclosures:
No relevant conflicts of interest to declare.
Rapid Diagnosis of Multidrug Resistance In Leukemia by Electrochemical Biosensor Based on Carbon Nanotubes–Drug Supramolecular Interaction
Authors: Chen Bao-An , Zhang Hai-jun , Wang Xue-mei , Jiang Hui , Gao Chong , Gao Feng , Ding Jia-hua , Cheng Jian , Song Hui-hui , Wang Jun , Bao Wen , Sun Yun-yu 
Published: October 2019

Abstract
Abstract 4856

Objective:
The multidrug resistance (MDR) in leukemia is a major chemotherapy obstacle, rendering many currently available chemotherapeutic drugs ineffective. The aim of this study was to explore the new strategy to early diagnose the MDR by electrochemical biosensor based on carbon nanotubes–drug supramolecular interaction.

Methods:
The carbon nanotubes modified glassy carbon electrodes (CNTs/GCE) as a sensor were directly immersed into the cells suspension of the sensitive leukemia cells K562 and/or its MDR cells K562/A02 to detect the response of the electrochemical probe of daunorubicin (DNR) residues after incubated with cells.

Results:
The fresh evidence from the electrochemical studies based on CNTs/GCE demonstrated that the homogeneous, label-free strategy could directly measure the function of cell membrane transporters in MDR cancer cells, identify the cancer cell phenotype (sensitive or MDR). The cathodic peak current showed good linear response to the changes of the fraction of MDR with a correlation coefficient of 0.995 when we further took the different ratios of the sensitive leukemia cells K562 and its MDR ones K562/A02 as the model of MDR levels to simulate the MDR occurrence in leukemia. Then, we can easily predict the MDR fraction based on the calibration curve of the cathodic peak current versus the fraction of MDR according to the obtained peak current.

Conclusion:
These results indicated that the biosensing assay could provide a powerful tool for assessment of MDR in leukemia. The new electrochemical biosensor based on carbon nanotubes–drug supramolecular interaction could represent promising approach in the rapid diagnosis of MDR in leukemia.

Disclosures:
No relevant conflicts of interest to declare.
Predictive Factors of Response and Survival Following Chemotherapy Treatment In Acute Leukemia with Complex Karyotype Aberrations
Authors: Ye Xiujin , Zhu Lixia , He Chunyuan , Zhu Jinjin , Li Li , He Jingsong , Zhang Jie , Huang He , Cai Zhen 
Published: October 2019

Abstract
Abstract 4857

Background:
Acute leukemia (AL) is a clonal hematopoietic stem cell disorder with diverse genetic abnormalities and various responses to treatment. AL was categorized into favorable, intermediate and adverse karyotype according to cytogenetic characteristics comprising different groups of patients with similar treatment response, relapse risk and overall survival. In particular, Patients with complex chromosome aberrations (CCA) harboring three or more acquired chromosome aberrations always have poor outcomes. It is necessary to investigate the clinical and laboratory features of AL patients with CCA, and to explore the underlying mechanisms of leukemogenesis in order to improve prognosis in these patients.

Methods:
83 AL patients with CAA were investigated and other 83 AL patients with none-complex chromosome aberrations (N-CCA) were regarded as control group from January 2005 to August 2008. The diagnosis of AL was based on morphological picture, immunophenotypical analysis, and cytochemical studies and FAB criteria were used for AL subtype classifications. Karyotypes were also analysed using conventional G-banding method. After patients had comfirmed diagnosis with AL, corresponding induction and consolidation chemotherapy in the two groups were given. Finally the treatment efficacy and prognosis were assessed. All the statistical analyses were performed using Kaplan-Meier.

Results:
There was no significant difference about sex, age and peripheral blood parameters before treatment between AL patients with CAA and the control group during the same period (p>0.05). CD34 was expressed in 72.3% of the AL patients with CCA, significantly higher than that in the control group (37.4%)(p<0.01). CD34+ AL patients with CCA showed a lower complete remission (CR) rate than in CD34- cases (p<0.05). 3-years EFS and OS were shorter in CD34+ patients than in CD34- cases. Using Kaplan-Meier analysis, the median survival time of AL patients with CCA was only 9 months, significantly shorter than the control group (21.5 months). There was no significant difference between AML and ALL patients with complex chromosome aberrations about CR rate and the survive time.

Conclusion:
The prognosis of patients with complex karyotype who received chemotherapy was extremely poor. In view of this, such patients should be considered as a unique entity and separated from those with a non-complex adverse cytogenetic change. They maybe benefit to some extent from allogeneic stem cell transplantation in younger patients according to some related reports. CD34 was associated with CAA while the underlying mechanisms between them were unknown.

Disclosures:
No relevant conflicts of interest to declare.
Chronic Lymphocytic Leukemia: Evaluation of Cytogenetic Markers as Prognostic Factors
Authors: Carda Jose , Sousa Patricia , Olim Patricia , Magalhães Emília , Rito Luis , Afonso Rui , Luz Braz , Geraldes Catarina , Vivan Marilene , Cortesão Emília , Jorge Lénia , Sousa Isabel , Teixeira Adriana 
Published: October 2019

Abstract
Abstract 4860
Backgroud: Chronic lymphocytic leukemia (CLL) is one of the most frequent chronic lymphoproliferative disorders in Europe. It is characterized by persistent monoclonal lymphocitosis with localized or generalized lymphadenopathy. Despite the initial clinical presentation, it has a heterogeneous natural history, with the majority of patients living 10–12 years, but with some patients dying rapidly, within 2–3 years of diagnosis. Beside clinical prognostic factors, novel cytogenetic markers are recognized to be useful in predicting disease free and overall survival in CLL.
AIMS: In a retrospective study throughout 10 years (1999-2009), we analyzed the clinical and biological presentation and compared the evolution and survival of patients with B-CLL using different cytogenetic markers.
METHODS: We identified 112 cases (63 males and 49 females) of B-CLL with cytogenetic study by fluorescence in situ hybridization (FISH).
RESULTS: Amongst 112 patients, the male to female (M/F) ratio was 1.3:1 and the median age was 70 (43-96) years. At diagnosis, the median lymphocyte count was 15.5 G/L (5.4-173). Fifty five patients (49%) had lymphadenopathies and seventeen (15%) had splenomegaly and/or hepatomegaly at presentation. By the revised Rai staging system seventy (63%) patients were included in low risk group, thirty (27%) in intermediate risk group and twelve (10%) in high risk group. The expression of ZAP-70 and CD38 by flow citometry was performed in 75 patients and revealed 13 (17%) patients CD38+ and 12 (16%) ZAP70+. The study of chromosomal aberrations with FISH showed thirty six patients (32%) with no abnormality, thirty six (32%) with isolated 13q deletion, fifteen (14%) with 12 trisomy, twelve (11%) with 11q deletion and thirteen (11%) with 17p deletion. Forty (36%) patients showed progressive disease in a median time of sixteen months (0-120), thirteen with 13qdel, seven with 17pdel and five with 12 trisomy. After treatment two patients showed progressive disease, six maintain a stable disease and thirty two obtain a remission, nine in complete remission. The Overall Survival (OS) at ten years was 70%. By the revised Rai staging system the OS at ten years was 80% for low risk, 70% for intermediate risk and all the high risk patients died during follow up. The OS at five years for the del13q-, 12 trisomy, del11q- and del17p- was 90%, 88%, 58% and 60%, respectively.
SUMMARY: Chronic lymphocytic leukemia is currently considered a chronic disorder with a favourable outcome, but with a variable evolution to progressive disease. This retrospective study allowed the characterization of patient with CLL in our department and the acknowledgement that our results are quite similar to the published data.

Disclosures:
No relevant conflicts of interest to declare.
Prologed Use of Pegylated Liposomal Doxorubicin In An HIV-Infected Population with Kaposi's Sarcoma at An Inner-City Safety Net Hospital
Authors: Gaddh Manila , Fokum Bernice , Bouiri Hamid , Haidau Augustin , Telfer Margaret 
Published: October 2019

Abstract
Abstract 4873

Introduction:
Kaposi's sarcoma (KS) is a low-grade HHV-8 associated vascular tumor that is particularly prevalent in patients infected with HIV. The mainstay of treatment is HAART, which has decreased the aggressiveness, and possibly the prevalence of this disease. Cytotoxic chemotherapy is generally added for moderate to severe symptomatic disease, with Pegylated Liposomal Doxorubicin (Doxil) being the treatment of choice. Studies have shown that unlike regular anthracyclines, Doxil can be safely administered over long periods at low doses without inducing cardio toxicity. The present study was done to evaluate cardiac toxicity associated with prolonged administration of Doxil in patients with KS.

Methods:
Seven-year retrospective chart review of 55 KS patients treated with 20mg/m2 of Doxil every 3 weeks until disappearance of lesions, withdrawal or change of treatment, or discovery of cardiac damage by annual MUGA scans. All patients received HAART concomitantly. In general, compliance was good. All presenting patients were male with one genetic male transsexual.

Results:
The median age of patients was 40 years; range between 25 – 56 years.
5 patients died during the study; 3 due to infectious complications and 2 due to heart disease. 7 patients had to discontinue Doxil when LVEF decreased to < 50%. Of the 16 patients who received >500mg/m2 Doxil, 1 died of cancer and 3 were switched to other drugs due to low LVEF. 1 of these 3 patients with decreased LVEF had a severely abnormal MUGA which then led to the diagnosis of coronary artery disease. The other 12 in this subgroup remain alive with no evidence of heart disease.

Conclusion:
In concordance with prior studies, our study shows that patients can tolerate greater than 500mg/m2 of cumulative Doxil dose, while being monitored closely with physical examination and MUGA scans. Obtaining MUGA scans every 6 months, instead of annually as was done in our study, may lead to earlier recognition of cardiotoxicity.

Disclosures:
No relevant conflicts of interest to declare.
Study of the Quantity and Function of Th17 Cells In the Hemocytopenic Patients with Positive BMMNC-Coombs Test
Authors: Fu Rong , Wang Honglei , Shao Zonghong , Wang Jun , Li Lijuan , Liu Hui 
Published: October 2019

Abstract
Abstract 4874

Objective
To explore the role of Th17 cells in the pathogenesis of IRP. Methods Forty-three untreated IRP patients, 34 recovered IRP patients and 13 healthy donors were enrolled in this study. The ratio of IL-23R+CD4+/CD4+cells in bone marrow were examined with flow cytometry (FCM). The levels of IL-6, IL-23, IL-17 were measured with ELISA. The expressions of RORγt mRNA ASTAT3 mRNA in BMMNC were measured by semiquantitive RT -PCR. Results The ratio of IL-23R+CD4+/CD4+ cells, the levels of IL-6, IL-23, IL-17 and the expressions of RORγt mRNA and STAT3 mRNA in BMMNC of untreated IRP patients were significantly higher than those of recovered IRP patients (p<0.05); there was no significant difference between those of recovered IRP patients and normal controls (p>0.05). There were significantly positive correlations between the ratio of IL-23R+CD4+/CD4+ cells and CD5+CD19+/CD19+ (p <0.05). There were significantly positive correlations between the levels of IL-17 and CD5+CD19+/CD19+the quantity of BMMNC–antibody (p<0.05); There were significantly positive correlations between the expressions of RORγt mRNA and the ratio of CD5+CD19+/CD19+, the quantity of BMMNC-antibody (p <0.05). There were significantly positive correlations between the ratio of IL-23R+CD4+/CD4+ and the level of IL-17, the expression of STAT3 mRNA (p<0.05). Conclusions There exists increased quantity and hyperfunction of Th17 cells in the IRP patients which induce B cells hyperfunction and production of autoantibodies against the BM hematopoietic cells. Th17 cells might be regarded as new therapeutic target of IRP.

Disclosures:
No relevant conflicts of interest to declare.
Liposomal Cytarabine (DepoCyte) Is Effective and Well Tolerated In Prophylaxis of Central Nervous System (CNS) Relapse of High Risk Lymphoma Patients
Authors: Jurczak Wojciech , Dzietczenia Justyna , Piatkowska-Jakubas Beata , Sobocinski Marcin , Ogorka Tomasz , Giza Agnieszka , Mazur Grzegorz , Wrobel Tomasz , Skotnicki Aleksander 
Published: October 2019

Abstract
Abstract 4890

Background:
CNS relapse is a devastating complication in patients with aggressive NHL and occurs in approximately 5 to 20% of cases. Preventing CNS relapse is an important goal of therapy in high-risk patients with aggressive NHL. The aim of this retrospective study was to evaluate safety and efficacy of Liposomal Cytarabine in a prophylaxis of CNS in high risk lymphoma patients.

Materials and Methods:
Data of patients treated with Liposomal Cytarabine within the last 2 years were retrieved from 2 centres in Poland which routinely administer prophylaxis of CNS in high risk NHL patients. 32 patients were included in this analysis: 26 – DLBCL including Primary Mediastinal B-cell Lymphoma (PMBCL), 2 – PTCL, 2 – LBL and 2 – BL. Demographics: average age: 42 (range 18–75), 12 females and 20 males. High risk was defined as the presence of elevated LDH (average 852 IU/L, range 482–1890 IU/L) and involvement of 2 or more extranodal sites, IPI 3–5 or specific lymphoma localizations (testis, vertebral column, orbits, sinuses, large mediastinal tumors over 10 cm in diameter). None of the patients had neurological symptoms at diagnosis, nor any abnormalities in cerebrospinal fluid analysis (average cellularity 4,7/mm3, range 0–18).

Results:
Liposomal Cytarabine was incorporated into 1st line systemic chemotherapy. On average, 3,4 doses (range 2–6) were applied every 2 (n=22) or 4 (n=10) weeks. Side effects: 18 out of 32 patients had no side effects. 12 patients experienced transitory, mostly mild, grade 1–2 adverse events; headache (n=10), nausea and vomiting (n=7), dizziness (n=4) or fever (n=3). Only 2 patients developed grade 3 headaches or fever. One patient developed transient neurological symptoms, most likely unrelated to Liposomal Cytarabine (vena cava superior syndrome at diagnosis and cerebralal thromboembolism after systemic immunochemotherapy).
After medium observation time of 306 days from the end of therapy (range 36 – 740) 28/32 (87,5%) patients were disease free. Three patients were lost due to systemic disease progression without any signs of CNS relapse on days 36, 101 and 182. One CNS relapse was reported on the day 252 (the patient subsequently died 5 months later).

Conclusions:
1) Liposomal Cytarabine is well tolerated, with mild or no adverse events. Its prolonged action allows it to be incorporated into a standard systemic anti-lymphoma therapy, without the necessity of additional hospital admissions.
2) In a described cohort of high risk lymphoma patients, Liposomal Cytarabine reduced the risk of early CNS relapse to 3% at 1 year (1/32 cases) and OS at 1 year 87% (28/32).

Disclosures:
No relevant conflicts of interest to declare.
Fludarabine, Aracytine and Rituximab Based Chemotherapy In Patients with Refractory and Relapsed Mantle Cell Non-Hodgkin Lymphoma
Authors: Perrone Tommasina , Gaudio Francesco , Giordano Annamaria , Curci Paola , Spina Alessandro , Risi Clara De' , Specchia Giorgina 
Published: October 2019

Abstract
Abstract 4892

Introduction
Mantle cell lymphoma (MCL) is a distinct B cell non Hodgkin lymphoma characterized by CD 5 expression, t (11; 14)(q13; q32) translocation and over-expression of Cyclin D1, and frequently has an aggressive clinical course. There is no standard of care for the treatment of MCL. Current treatment approaches are non curative and pts median survival is 4–6 years. Various studies have reported promising results for a high dose Cytarabine-containing regimen in the treatment of MCL. Fludarabine has also been recognized as effective treatment in pts with MCL, either as a single agent or in combination with other drugs. The addition of Rituximab improves the response to the treatment. The aim of this study is to assess the efficacy and toxicity of a combination of Fludarabine, Aracytine and Rituximab treatment in refractory and relapsed MCL.

Methods
We retrospectively evaluated 20 pts with refractory or relapsed MCL treated in our institution between February 2007 and February 2010.
Median age was 59 yrs (54-77 yrs), 14 pts (70%) were males, 18 pts (90 %) had stage IV, 16 pts (80%) had bone marrow involvement, 16 (80%) presented comorbidities. Eight pts (40%) were in first relapse, 12 (60%) in second relapse. Twelve pts (60%) had a “Mantle Cell Lymphoma International Prognostic Index” (MIPI) score ≥ 7. Therapy included: fludarabine 25 mg/m2/daily intravenously for 3 days, aracytine 500 mg/m2/daily for 3 days and Rituximab 375 mg/m2/daily for 1 day, Dexamethasone 8 mg daily for 3 days, every 28 days for 4 cycles.

Results
Eight pts (40%) achieved complete response (CR) and 4 pts (20%) a Partial Remission (PR) with an overall response rate (ORR) of 60%. Eight pts (40%) progressed and one of them died of active disease. After a median follow up of 17 months (range 8–36), OS is 70% and PFS is 55%.
Toxicity was mainly hematological with grade >=3 neutropenia in 40 (50%) of the 80 cycles performed, grade >=2 anemia in 30 (37%) and grade 4 thrombocytopenia in 24 (30%). In 16 (20%) cycles pts required red blood cells transfusions, in 12 (15%) platelet transfusions. One episode of Herpes Zoster infection was observed.

Conclusions
This study suggests that the combination of Fludarabine, Aracytine and Rituximab appears to be an effective regimen with a promising response rate and manageable toxicity, for pretreated pts often affected by comorbidities and with poor prognosis.
Further studies are needed to assess the efficacy of this combination therapy and to further test the role of this approach in MCL.

Disclosures:
No relevant conflicts of interest to declare.
The Effect of Adding Rituximab to CHOP-Based Therapy on Clinical Outcomes for Patients In Different Subgroups of DLBCL
Authors: Qian Shenxian , Gao Daquan , Shi Pengfei , Tan Junfeng , Wang Ling , Liu Lirong , Huang Xilian , Chang Kuang , Xie Yaping , Xu Ying 
Published: October 2019

Abstract
Abstract 4893
The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been shown to improve the outcome in all age groups with newly diagnosed diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis to evaluate the impact on clinical outcomes of adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for diffuse large B-cell lymphoma (DLBCL) patients in china. A propensity score method was used to compensate for the non-randomized study design. From January 2004 to December 2009, 68 patients were newly diagnosed with DLBCL Using Hans' algorithm based on CD10, BCL-6, and MUM1, the non-germinal center (N-GCB) subgroup 45(66.2%) and germinal center B-cell-like (GCB) 23(33.8%). 32 in the rituximab plus CHOP-based chemotherapy (R+) group, and 36 in the CHOP-based chemotherapy only (R-) group. The complete response rate was significantly higher in the R+ group than in the R- group (81.1 vs. 68.1%, P < 0.005,); The complete response rate of N-GCB and GCB in the R+ group was78.2% and 82.1%, p>0.05 respectively. The complete response rate of N-GCB and GCB in the R- group was58.2% and 71.3 %, p P < 0.001. The rituximab can overcome poor outcomes for N-GCB subgroup of DLBCL. The progression-free survival (PFS) at 2 years was 62.4% in the R+ group and 57.0% in the R- group. The 2-year overall survival (OS) was 76.9% for the R+ group and 69.5% for the R- group, P < 0.001. The 2-year overall survival (OS) was 72% in N-GCB Subgroup and 78% in GCB Subgroup for the R+ group, and 48% in N-GCB Subgroup and 68% in GCB Subgroup for the R- group. A multivariate analysis revealed that the addition of rituximab was a strong independent prognostic factor for PFS (hazard ratio 0.64, 95% CI 0.43–0.96, P = 0.031). A subgroup analysis revealed that R+ particularly benefited N-GCB subgroup patients). IPI also showed significant impact for PFS (hazard ratio 1.72, 95% CI 1.34–2.14 for one score increase, P < 0.001 as well as OS P < 0.001. In summary, the addition of rituximab to CHOP-based chemotherapy results in better outcomes for DLBCL patients, particularly patients N-GCB subgroup of DLBCL.

Disclosures:
No relevant conflicts of interest to declare.