bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescent and Young Adult (AYA) Cancer Survivorship Curriculum In a University Setting
Authors: Wood William , Wright Sarah , Stephens Anne , Santacroce Sheila , Blatt Julie , Shea Thomas C.
Published: October 2019

Abstract 4749

Background:

That pediatric, adolescent and young adult cancers have become compatible with long term survivorship in the majority of cases has meant a growing emphasis on an understanding of the late effects of treatment. Among the barriers to successful health self-management in the context of transition of care from pediatricians to internists is the challenge of finding adult health care providers in the community who are comfortable caring for patients in this age group. We have developed a curriculum relating to different aspects of AYA survivorship for oncology and primary health care trainees who may come across AYA cancer survivors in the course of usual practice. Focus groups were used to refine the modules before the current application.

Aim:

To improve provider knowledge of AYA survivorship issues and management in a university setting.

Methods:

Using a combination of review articles, original research, and published guidelines for cancer survivorship, 8 teaching modules (power point presentations of 8–15 slides each) were developed: health care self-management; bone health; cardiac late effects; fertility late effects; neurocognitive late effects; psychosocial late effects; pulmonary late effects; and second malignancies. Modules were refined with the use of provider focus groups. These recently have been made available to trainees at UNC: (pediatrics [P], medicine-pediatrics [MP], medicine [M], medical hematology oncology [MHO], pediatric hematology oncology [PHO], and nurse practitioner students [NP]) in hard copy and on departmental websites. Computerized pre- and post-tests were developed for each module to assess content acquisition and will be required of the ~6 trainees/month rotating through the Survivors Clinics or on inpatient or outpatient services. At the end of each module, participants also are being asked, using a 3 point scale (agree [3], neutral [2], disagree [1]) if they feel the sessions gave them increased confidence in following AYA survivors. Participants also will be given the opportunity to critique the modules.

Results:

Preliminary results will not be available until December. However, enthusiasm among the target audience during the first 2 months of this program has been strong.

Conclusion:

Short teaching modules can be developed to engage trainees in AYA late effects issues. Ongoing work is being done to assess the effectiveness and usefulness of the modules for providers at UNC who care for adolescent and young adult cancer survivors. We anticipate that this approach will be expanded to our outreach practices. Parallel modules are in development for AYA survivors and their families. *With support from a 2009 ASH Alternative Training Pathway Grant, T. Shea, PI.

Disclosures:

No relevant conflicts of interest to declare.
Hepatitis B Surface Antigen Seropositivity and Low Body Weight Are Correlated with Asymptomatic Neutropenia In the Thai Population
Authors: Lawasut Panisinee , Nakorn Thanyaphong Na , Rojnuckarin Ponlapat , Intragumtornchai Tanin
Published: October 2019

Abstract 4751

Background

The etiology of asymptomatic neutropenia is unknown. We have conducted a community-based study to determine predisposing factors for asymptomatic neutropenia in the Thai population.

Method

Blood specimens and self-report questionnaires (filled out with assistance from medical personnel) were collected from individuals in Bangkok and 4 surrounding provinces. Asymptomatic neutropenia was defined by an absolute neutrophil count of less than 1.5 × 109/liter, in the absence of any symptoms or known risk factors. Patients with a history of malignancy were excluded. Subjects that met this criterion for neutropenia were examined for the presence of anti-HIV and anti-hepatitis C virus (HCV) antibodies, hepatitis B surface antigen (HBsAg), antinuclear antibody (ANA), rheumatoid factor (RF), thyroid dysfunction, reduced serum ferritin, and reduced serum vitamin B12 and folate; this panel of laboratory tests was also done on control subjects (4 controls for every 1 neutropenic case – see below), which were picked at random from the normal population and were matched for age, sex, site of survey, and underlying disease. Odd ratios (OR) were then computed for significant risk factors.

Results

Overall, 7,180 individuals were included; 28 had neutropenia (0.39%, 95% CI 0.25–0.53). Based on answers to the questionnaire, the only factor correlating with neutropenia was low body weight (body mass index < 18.5 kg/m2, p = 0.015); age, sex, site and period of survey, underlying disease, medications, herbal ingestion, food supplement, radiation exposure, family history of hematologic disease, alcohol consumption, history of drug abuse or exposure to chemical substance had no significant association with neutropenia. Additional tests on 25 of the neutropenic cases revealed positive findings for HBsAg (20%), anti-HCV antibody (12%), ANA (16%), RF (4%), hypothyroidism (4%), hyperthyroidism (14%) and hypoferritinemia (24%); none showed anti-HIV positivity, or low levels of serum vitamin B12 and folate. Of the 100 normal controls, 4% showed seropositive for HBsAg. HBsAg positivity was thus the significant risk factor associated with neutropenia (OR 6.0, 95%CI 1.48–24.34, p = 0.012).

Conclusion

HBsAg seropositivity is strongly associated with asymptomatic neutropenia in the Thai population. Low body weight is also correlated with the disorder, perhaps as a result of subtle nutritional deficiencies. Possible mechanisms that underlie neutropenia are currently being explored.

Disclosures:

No relevant conflicts of interest to declare.
Assessing the Experience of Living with Chronic Myeloid Leukemia (CML) From the Patient's Perspective: Results of a Patient Survey
Authors: Victor Timothy W , Hirji Ishan , Hicks Ian , Chapnick Jonathan , Davis Catherine , Bahceci Erkut
Published: October 2019

Abstract 4755

Background:

While clinical outcomes among CML patients have shown great improvement with the development of TKIs, few studies have been conducted to assess the impact of CML and CML treatment from the perspective of CML patients. Information on CML treatment adherence and impact on quality of life (QoL) has been captured in the context of clinical trials with QoL being measured using generic measures. Very little is known about patient experience of CML and CML treatment in the real-world setting.

Objective:

To assess the impact of CML and CML treatment on daily productivity, quality of life and treatment adherence, from the patientâ|CE™s perspective.

Method:

In a pilot survey, twenty patients diagnosed with CML described their experiences in single 45 minute interviews conducted via telephone. Eligible patients included adults (>18 years) diagnosed with chronic phase CML and either currently on oral treatment for their CML or on drug holiday. Questions included in the pilot survey addressed overall treatment satisfaction, ease/burden of daily treatments and impact of treatment on daily activities. A preliminary analysis of 16 patients included in the pilot study was conducted.

Results:

Mean patient age was 52.9 years (SD = 12.6), 56.3% were male, averaged 3.1 years since diagnosis (SD = 3.1). Patientsâ|CE™ satisfaction with their oral CML treatment was high (mean 9.3 on a scale of 1 – 10, where 1 = not at all satisfied and 10 = very satisfied, SD = 1.3) among the 14 patients who provided a score. Perception of having a favorable response to treatment was also high (14/16). While patients reported good adherence to their treatment regimens, 9/16 patients mentioned missing doses of their CML treatment. Constitutional symptoms of treatment were reported as a daily occurrence by 50% of patients (8/16).

Conclusion:

In this pilot survey of the CML patientâ|CE™s perspective, high patient satisfaction with oral CML treatments was primarily attributable to a high overall response to treatment. Willingness to adapt to certain aspects of CML treatment was high given that treatment was perceived as being life-saving. Understanding factors which could minimize the impact on daily activities is important as new treatment options become available. Results from this pilot survey will inform the content of a self-administered questionnaire to include an expanded cohort of CML patients (n=300) within the US and Europe.

Disclosures:

Victor: Bristol-Myers Squibb Company: Research Funding. Hirji:Bristol Myers-Squibb: Employment. Hicks:Bristol-Myers Squibb Company: Research Funding. Chapnick:Bristol-Myers Squibb Company: Research Funding. Davis:Bristol Myers-Squibb: Employment.
Metformin Selectively Suppressed the Proliferation of AML Stem Cells through Increased Phosphorylation of AMP-Activated Protein Kinase
Authors: Shin Myung-Geun , Eom Ha-Young , Kim Hye-Ran , Shin Jong-Hee , Suh Soon-Pal , Ryang Dong-Wook
Published: October 2019

Abstract 4771

Background:

Leukemic stem cell (LSC) has been accused to play a pivotal role in pathogenesis of hematological malignancy such as acute myeloblastic leukemia (AML). AML stem cell (ASC) is known as CD34+CD38– leukemic cell population. Yet, despite their critical importance, much remains to be learned about selectively targeting ASC. Recently metformin selectively targets breast cancer stem cells, and acts together with chemotherapy to block tumor growth. Thus, the current study investigated whether metformin selectively inhibits AML cells and AML stem cells directly or indirectly.

Materials and Methods:

ASC showing CD34+CD38– phenotype were selectively sorted from primary bulk AML cells and KG-1 AML cell lines using single cell sorter (BD FACS Aria cell sorter, BD Biosciences, USA). ASC from primary AML samples and cell lines were cultured in serum media with each 100 ng/mL of stem cell factor, Flt-3, thrombopoietin and G-CSF. Metformin (1,1-dimethylbiguanide hydrochloride) and idarubicin (IDA) were dissolved and diluted with high purity distilled water in various concentrations (0.1 mmol/L to 30 mmol/L). Morphological change, cell count, viability and apoptosis using annexin V flowcytometry were checked after treatment of metformin and IDA. Phosphorylation of AMPK was assayed by western blotting and mitochondrial membrane potential was measured using MitoTracker green dye.

Results:

The frequency and proportion of ASC varied according to FAB subtypes. The mean proportion of ASC from AML M2, M4 and M3 showed 25.1±22.5% (mean±SD), 15.1±16.6% and 6.5±3.3%, respectively. The mean proportion of ASC from KG-1 cell lines was 78.6±6.2%. Total cell count of ASC was gradually decreased after treatment of metformin in dose-time dependent manner. Overall viability of AML cell lines and ASC disclosed significant decrease after treatment of metformin. The proportion of apoptosis was increased in time and dose dependent manner after 24-hr treatment of metformin. Mitochondrial membrane potentials were increased after metformin exposure at dose dependent manner. Moreover, when combined with lower concentration of IDA, more profound selective killing effect on AML cell lines and ASC was observed. Western blot analysis showed that the treatment of AML cell lines and ASC with 30 mmol/L of metformin resulting in the increased phosphorylation of AMP-activated protein kinase (AMPK) at approximately 1.5-fold over total AMPK.

Conclusion:

Metformin selectively kills AML cells as well as AML stem cells, and acts together with chemotherapeutic drugs to eradicate leukemic cells and their stem cells.

Disclosures:

No relevant conflicts of interest to declare.
Microarray Analysis of CD34+CXCR4+ and CD34+CXCR4- Cells Reveals Two Distinct Hematopoietic Stem/Progenitor Populations
Authors: Donahue Robert E , Jin Ping , Tian Yu , Allen Robyn S , Bonifacino Aylin , Stroncek David
Published: October 2019

Abstract 4798

Although CD34+ cells represent a small population of phenotypically defined cells within the bone marrow and peripheral blood circulation, they remain a very heterogeneous population of cells which contain hematopoietic stem/progenitor cells. CXC Chemokine Receptor 4 (CXCR4) is an α-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12) and is found on CD34+ cells. Plerixafor (also known as Mozobil® or AMD3100) is currently used as a mobilizing agent for CD34+ cells by interfering with the binding of CXCR4 to SDF-1. To explore differences between CD34+CXCR4+ and CD34+CXCR4- populations, gene and microRNA signatures were determined using microarray analysis. Three healthy human donors were cytokine mobilized with G-CSF, peripheral blood mononuclear cells were collected by apheresis, and CD34+ cells were immunoselected using the Miltenyi CliniMACS® system and cryopreserved. These cells were then thawed and allowed to sit overnight at 37°C in X-Vivo-10. The following day the cells were stained and sorted on a BD FACSAria III® cell sorter. All three individuals CD34+CXCR4+ and CD34+CXCR4- fell within two rather restrictive populations based on forward and side scatter gating with CD34+CXCR4+ cells routinely being smaller in size than the CD34+CXCR4- populations (Figure 1). Total RNA was isolated from the sorted cells and amplified to cRNA. Control cRNA was labeled with Cy3 dye and experimental cRNA was labeled with Cy5 dye and co-hybridized to a custom-made 17.5K cDNA (UniGene cluster) microarray. Using unsupervised and supervised Eisen's hierarchical clustering and Array Class Comparison analysis relationships were determined. Hierarchical cluster analysis demonstrated that the CD34+CXCR4+ and CD34+CXCR4- had different gene expression patterns (Figure 2). Ingenuity Pathway Analysis revealed that genes up-regulated in the CD34+CXCR4+ population were related to TREM-1 signaling (innate immunity), dendritic cell maturation, NFAT-regulation of the immune response, and T-cell receptor and NK cell signaling. In contrast, the CD34+CXCR4- population expressed more primitive genes such as those related to IGF-1, ERK/MAPK, IL-3, and Nitric Oxide signaling as well as transcription factors such as N-myc and HOX-A9. MicroRNA profiling of the CD34+CXCR4- population also express the miR-17-92 polycistron cluster (miR17, 18a, 19a, 19b, 20a, 92) (Figure 3). These results are consistent with the CD34+CXCR4- population being more primitive than the CD34+CXCR4+ population. It is interesting to speculate whether the CD34+CXCR4+ population includes a progenitor for T cell and innate immune responses while progenitors for hematopoietic stem cells and adaptive immune responses are within the CD34+CXCR4- populations.

Disclosures:

No relevant conflicts of interest to declare.
Analysis of Calcium Profile and Bone Mineral Density in Patients with Sickle Cell Disease
Authors: Gonçalves Lucila Macedo , Cancado Rodolfo , Petry Tarissa Beatrice Zanata , Melo Murilo Rezende , Salles João Eduardo , Scalissi Nilza Maria , Chiattone Carlos
Published: October 2019

Abstract 4810

Introduction:

Sickle Cell Disease (SCD) is a genetic disorder where the red blood cells assume an abnormal, rigid, sickle shape, causing tissue hypoxia with subsequent increase of osteoclastic activity, originating osteopenia and osteoporosis. The prevalence of the osteoporosis in the SCD can vary from 25 a 50%, affecting more commonly the children. There are few data regarding the prevalence of bone mineral low density in adults. Our objective was to analyse the calcium profile and bone mineral density (BMD) of pacients with SCD and describe the prevalence of osteopenia in this group.

Material and Methods:

We have studied 49 patients with SCD analysing the serum and 24 hours urinary calcium, serum ferritin, LDH, parathyroid hormone (PTH) and BMD in the lombar vertebrae and proximal femoral.

Results:

From the 49 patients, 21(42.9%) were males and 28(57.1%) females, mean age of 27 years old (16-51 yr), 55.1% (27) of the patients presented osteopenia and 26.5% (13) osteoporosis, considering lombar vertebrae BMD. Only 18.4% (9) had normal BMD. Mean ± DP PTH was 85.3 ± 79.32 and mean ± DP serum calcium of 8.9 ± 0.44. Mean ± DP LDH was 970.8 ± 492.36 and we have observed significant correlation between this variable and low BMD (p<0.02).

Conclusion:

The prevalence of osteopenia and osteoporosis was extremely high (81.6%) in the studied patitents. The secondary hyperparatireoidism was present in many patients and we did not find hypoparathyroidism. The hemolysis appears as a factor that contributes for the low BMD.

Disclosures:

No relevant conflicts of interest to declare.
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 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 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 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 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 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 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 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 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 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.
Is Rasburicase Effective In Reversing Acute Renal Failure In Patients with Tumor Lyses Syndrome?
Authors: Cherry Mohamad Ali , Srour Samer , Khawandanah Mohamad , Qubaiah Osama , Ghabache Bassam
Published: October 2019

Abstract 4939

Tumor lysis syndrome (TLS) is a potentially life-threatening complication that can occur spontaneously or following treatment of malignant neoplasms, particularly leukemias and lymphomas. TLS can cause acute renal failure (ARF) by precipitation of uric acid (UA) and phosphate crystals in renal tubules. Rasburicase, a recombinant urate oxidase, was proven to be effective in the treatment of TLS and is known to cause an improvement in renal function in a subset of patients with TLS. For the purposes of our analysis ARF was defined as more than 50% increase in creatinine from baseline value or presenting with creatinine more or equal to 2 mg/dl with no previous history of chronic renal failure. To assess the efficacy of Rasburicase in adult patients with documented TLS and ARF in improving or normalizing the creatinine clearance (CrCl), we conducted a retrospective analysis of 53 patients that received Rasburicase for documented TLS. 41 patients fit the inclusion criteria. The median age was 54 yr (26-90), 13 were female. The majority of patients had hematological malignancies (acute leukemia, 11; chronic leukemia, 5; myeloproliferative/myelodysplastic syndromes, 4; lymphoma or myeloma, 10; solid tumor; 11).

Results: On the first day of rasburicase infusion (day 0), median UA, creatinine and CrCl were 11.5 mg/dl (5.1 - 23.7mg/dl), 3.26 mg/dl and 32.5 ml/min (8.0 - 97.8 ml/min) calculated using Cockcroft-Gault equation, respectively. Patients received an average total dose of 0.17 mg/kg (0.06-0.51 mg/kg) of rasburicase in one or two doses. UA levels normalized in 97.3% and 100% of patients by day 2 and 7 respectively. Creatinine levels normalized in 19% and 59.4% by day 2 and 7 respectively. CrCl improved form a median of 32.5 ml/min to 40.5 ml/min and 58 ml/min by day 2 and 7 respectively. A sub analysis for patients with baseline CrCl <30 ml/min (n=17) on day 0 of Rasburicase infusion revealed a similar benefit to those with baseline CrCl >30 ml/min. CrCl improved in this subset of patients from a median of 17 ml/min (8-28.2 ml/min) to 24.5 and 47.4 ml/min on days 2 and 7 respectively. Patients who received a total dose of <0.1mg/kg of rasburicase (n=8) derived similar benefits to those who received 0.2mg/kg or more (n=11).

Conclusion: Rasburicase infusion is effective in improving the creatinine clearance even in patients with advanced renal failure (CrCl<30 ml). Lower doses of Rasburicase are as effective as higher doses, even in patients with advanced renal failure, making the lower dose advisable and cost effective.

Disclosures:

No relevant conflicts of interest to declare.
Synthesis and Reversal Efficacy of Magnetic Nanoparticles Coloaded with Daunorubicin and 5-Bromotetrandrin
Authors: Chen Bao-An , Wang Jun , Cai Xiao-hui , Gao Feng , Cheng Jian , Chen Ping-shen , Zhang Yu , Tang Meng , Ding Jia-hua , Bao Wen
Published: October 2019

Abstract 4945

Owing to serious side effects and multidrug resistance (MDR), systematic chemotherapy is limited in cancer treatment. On the one hand, most of side effects are result from non-selective for target cells of antitumor drugs. On the other hand, the main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). Design and exploitation of novel clinical chemotherapy formulation with dual functional properties of targeted therapy and reversal of drug resistance is a promising approach in tumor therapy. Nanoparticles drug delivery system has been shown to improve cancer therapy by increased drug delivery to target sites because of the enhanced permeability and retention effect (EPR). In the present studies, we developed a new formulation, which magnetic nanoparticles (MNPs) coloaded with daunorubicin (DNR) and 5-bromotetrandrin (Br Tet), an anticancer drug and a MDR reversal agent, and studied the in vitro antitumor efficacy. The drug encapsulation efficiency of DNR and Br Tet (alone or in combination) in MNPs was 62–83%. The release of DNR and Br Tet from nanoparticles was sustained. The DNR and Br Tet loaded MNPs (DNR-Br Tet-MNPs) are provided with good magnetic responsibility. The drugs in combination incorporated in MNPs displayed well synergistic cytotoxicity in the MDR leukemia K562/A02 cells. Fluorescence intensity of intracellular DNR detection demonstrated that DNR-Br Tet-MNPs could be endocytosed by K562/A02 cells and sustained releasing DNR intracellular. The results of RT-PCR and western blot demonstrated that the expressions of MDR1 mRNA and G-pg of K562/A02 cells are decreased by treated with DNR-Br Tet-MNPs after 48 h. It was concluded that the antitumor efficacy of DNR-Br Tet-MNPs was due to the inhibition of Br Tet to P-gp and reducing the efflux of DNR. Our DNR-Br Tet-MNPs could be of high clinical value in the target treatment of many resistant tumors, such as haematologic malignancies.

Disclosures:

No relevant conflicts of interest to declare.
IL-4 and IL-1 Serum Levels In Systemic and Localized Amyloidosis
Authors: Moscetti Alessandro , Saltarelli Francesca , Bruno Guglielmo , Monarca Bruno , Salerno Gerardo , Corsetti Maria Teresa , Cardelli Patrizia , Ferranti Giovanna , La Verde Giacinto
Published: October 2019

Abstract 5000

AL amyloidosis is a plasmacellular discrasia characterized by the deposition of light chains fibrils that infiltrate tissues leading to multisystemic organ involvement. Amyloidosis can be systemic or localized disease. No immunological markers are avaibable to distinguish the systemic from localized disease. IL-4 and IL-1 cytokines were performed to evaluate if there is a different inflammatory pattern between the two clinical forms. IL-4 is the central regulator of T helper 2 (Th2) immune responses, with also a major impact on innate immune cells. IL-1 is produced by macrophages, monocytes, fibroblasts and dendritic cells which play an important role in the inflammatory response, activating the Th1-mediated IL2 release. IL-1 increases the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes to sites of infection. The study was devoted to evaluate serum levels of IL-4 and IL-1 in systemic or localized AL amyloidosis at presentation and to find out potential Th1 and Th2 disequilibrium. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. Serum IL-4 and IL-1 levels were detected. Mann-Whitney test and correlation test were used to analyze results. IL-4 level was significantly (p < 0.05) higher in patients with localized disease compared to the group with systemic amyloidosis. IL-1 was instead significantly (p < 0.01) increased in systemic disease. In this, an inverse correlation between IL-4 and IL-1a was found (r2= –0.707; p = 0.05). In systemic amyloidosis, the regulatory mechanism of Th1/Th2 response was polarized versus Th1, as demonstrated by low serum level of IL-4 and high level of IL-1. The negative correlation between serum IL-4 and IL-1 levels demonstrates a disregulation of the immune system in systemic disease as supported by the increased activity of Th1. The results seem to hypothesize that IL-4 could be able to antagonize the diffusion of disease, as demonstrated by the higher IL-4 serum levels in localized amyloidosis. So IL-4 and IL-1 can be considered sensible markers for the inflammatory response assessment both in systemic and localized amyloidosis.

Disclosures:

No relevant conflicts of interest to declare.