Division Of Hematology Research Articles

1069P - Phase II study of biweekly TPFL induction chemotherapy for locally advanced squamous cell carcinoma of head and neck

Background: The induction chemotherapy (ICT) with triweekly TPF had been considered as an effective treatment in locally advance squamous cell carcinoma of head and neck (SCCHN). However, the treatment needs inpatient care and may have more toxicities for Asian patients. We conducted a phase 2 study of alternative biweekly TPFL as induction chemotherapy and evaluated the outcome and toxicities. Methods: Patients with locally advanced SCCHN were enrolled in the study. Induction chemotherapy with Docetaxel 50mg/m2, cisplatin 50mg/m2, 5-fluorouracil 2500 mg/m2 and leucovorin 250 mg/m2 was administered biweekly for six cycles, followed by local treatment including concurrent chemoradiotherapy, bio-radiotherapy or surgery plus adjuvant RT. Our primary endpoint is response rate after ICT. Results: Total 58 patients were enrolled in the study from June 2014 to September 2015. The median age is 53 years (from 28 to 69 y/o). The patients’ characteristics was mentioned as: primary site of oral cavity/oropharynx/hypopharynx: 18/25/15; stage IVa/IVb: 35/23; male /female: 54/4; performance status ECOG 0-1/2:57/1. In the oropharyngeal cancer patients neither p16 nor HPV16 status was not studied. Of those 58 patients, 56 patients received at least 4 cycles of chemotherapy. The overall response rate after ICT was 89.6 % (CR: 31% PR: 58.6%). Two patients escaped during induction chemotherapy. Grade 3/4 neutropenia was 25/9%; grade 3/4 mucositis was 1.7%; grade 3/4 diarrhea was 1.7%. Infection rate was 19%. The response rate after following treatment was 75 % (CR: 66.0%, PR: 9.0 %) The median follow-up time was 31.8 months. The overall 3 years PFS/OS was 34.3 %/56.1%. Local recurrence rate was 29.3% and distant metastasis rate was 10.3%. Six patients had second primary tumor. (10.3%) The 3 years PFS of patients with CR/PR were 59.3%/25.5%. The 3 years OS of patients with CR/PR were 81.7%/49.1%. Conclusions: Biweekly TPFL induction chemotherapy has excellent response rate in locally advanced SCCHN. In addition, the grade 3/4 adverse event was acceptable. The patients achieved CR after induction chemotherapy had very good outcomes. Clinical trial identification: CMUH103-REC2-038. Legal entity responsible for the study: Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital. Funding: Sanofi, Taiwan branch. Disclosure: All authors have declared no conflicts of interest.

Whole-Body Lung Function Test–Derived Outcome Predictors in Allogenic Stem Cell Transplantation

Despite clinical advances, late onset pulmonary complications in adult recipients of allogenic stem cell transplantation are a major cause of morbidity and mortality. Reported incidence and risk factors in the literature vary broadly and are partly contradictory. Identification of pretransplant factors associated with major complications would be helpful to define individual treatment strategies and early initiation of preventive measures.To evaluate incidence and risk factors of late onset noninfectious pulmonary complications, with special regard to small airways disease (SAD) and bronchiolitis obliterans syndrome (BOS), indicating graft-versus-host disease, following myeloablative versus nonmyeloablative allogenic stem cell transplantation.We reviewed the clinical records and assessed the course of lung function and pulmonary complications in adults who underwent allogenic stem cell transplantation for hematological malignancies between 1999 and 2015 using nonmyeloablative (n = 179) or myeloablative (n = 130) conditioning at the Division of Hematology of the Medical University of Graz. All patients underwent body plethysmography pulmonary function test (PFT), diffusion capacity for carbon monoxide, and arterial blood gas analysis before and repeatedly after transplant. SAD was defined as maximal expiratory flow at 50% and 25% of forced vital capacity <70% predicted.Ventilatory disorders and gas transfer abnormalities were common before and after allogenic stem cell transplantation, independent of conditioning regimen. SAD was common in the nonmyeloablative (34%) and myeloablative (29%) groups. The 100-day post-transplant mortality was significantly associated with reduced pretransplant total lung capacity <80%. Mortality 100 days post-transplant was significantly associated with pretransplant SAD and a pretransplant smoking history. In this subset, a smoking history was independently associated with increased mortality, with a 5-year mortality of 45% compared with 26% in never-smokers. Pretransplant SAD was not predictive for the later development of BOS.Smoking history, pretransplant restrictive PFT, and pre-existing SAD are important risk factors for death following allogenic stem cell transplantation. However, pretransplant SAD is not a predictor of long-term complications, including BOS.

Highlights From the Circulation Family of Journals.

Highlights From the Circulation Family of Journals.

Systemic Large-Vessel Vasculitis and Retroperitoneal Fibrosis in the Setting of T-Cell Chronic Lymphocytic Leukemia

Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada [email protected] Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada Division of Rheumatology, Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada The authors declare no conflict of interest.

Impact on platelet recovery of recombinant human thrombopoietin in severe aplastic anemia patients with allogeneic hematopoietic stem cell transplantation

目的分析重组人血小板生成素（rhTPO）促进重型再生障碍性贫血（SAA）患者异基因造血干细胞移植（allo-HSCT）后血小板恢复的疗效及安全性。方法对2010年1月至2017年3月期间85例接受allo-HSCT治疗的SAA患者进行回顾性分析。根据移植后升血小板药物的使用情况，将85例患者分为rhTPO组（29例）、rhIL-11组（27例）和空白组（29例），比较三组PLT≥20×109/L、PLT≥50×109/L、PLT≥100×109/L的恢复时间以及移植后（25±5）d骨髓巨核细胞计数、移植期间血小板输注量，观察药物不良反应。结果rhTPO、rhIL-11、空白组粒细胞植入和PLT≥20×109/L的中位时间差异均无统计学意义（P>0.05）。rhTPO组PLT≥50×109/L时间短于空白组[16.5（11~39）d对22（14~66）d，P<0.05]；rhTPO组PLT≥100×109/L时间[23（12~51）d]短于rhIL-11组[28（12~80）d]及空白组[35（18~86）d]（P<0.05）。rhTPO组移植期间血小板输注量少于rhIL-11组及空白组[分别为20（10~30）、30（10~50）、35（10~70）U，P<0.05]。rhTPO、rhIL-11、空白组移植后（25±5）d骨髓巨核细胞中位计数分别为31.5（0~200）、12（0~142）、11（0~187）个，rhTPO组与rhIL-11组比较差异有统计学意义（P<0.05），rhIL-11组与空白组比较差异无统计学意义（P>0.05）。多因素分析显示，应用rhTPO是影响血小板恢复的独立影响因素[HR=4.01（95%CI 1.81~8.97），P=0.010]。rhTPO组未见明显不良反应。结论rhTPO可以促进SAA患者allo-HSCT后血小板恢复、减少血小板输注量，并且安全性较好。

Monitoring response rate of blood donors concerning positive screening tests for HIV and syphilis: an institutional approach toward donor hemovigilance

Objective To investigate the response rate among our blood donors when notified about their positive screening results of HIV and syphilis. Study setting An observational study conducted at a Division of Hematology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital from January 2013 to December 2014. Materials and methods Computerized donor inventory data were retrieved. The frequency of screening-positive donors for HIV and syphilis was calculated and the donors were informed through telephone to provide fresh samples for confirmatory tests. The frequency of those donors who responded by providing fresh blood sample was computed. Results Of the total 1684 screening-positive doors, 255 were reactive for syphilis and 11 were reactive for HIV. Only 232 (91%) of the venereal disease research laboratory positive were successfully contacted, out of these only 65 (28%) gave fresh samples and treponema pallidum particle agglutination (TPHA) test results confirmed 56 (86%) donors as positive and nine (14%) as negative for syphilis. On the other hand, of the11 anti-HIV-reactive donors 10 (91%) were successfully approached, five (50%) donors showed a positive response by giving fresh samples for Western blot confirmatory test, which affirmed three (60%) donors to be positive and two (40%) donors to be negative for HIV. Conclusion The results reverberate the lack of awareness among our blood donors. Better predonation counseling can improve the overall outcome.

Durvalumab: an investigational anti-PD-L1 monoclonal antibody for the treatment of urothelial carcinoma.

Our expanding knowledge of immunotherapy for solid tumors has led to an explosion of clinical trials aimed at urothelial carcinoma. The primary strategy is centered on unleashing the immune system by releasing the inhibitory signals propagated by programmed cell death-1 (PD-1) and its ligand programmed cell death ligand-1 (PD-L1). Many antibody constructs have been developed to block these interactions and are used in clinical trials. The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab. One of the latest inhibitors is durvalumab, which is a high-affinity human immunoglobulin G1 kappa monoclonal antibody and blocks the interaction of PD-L1 with PD-1 and CD80. Currently, there are a number of ongoing trials in advanced urothelial carcinoma both using durvalumab monotherapy and in combination with other targeted therapies. In addition, durvalumab is being investigated in the non-muscle-invasive urothelial carcinoma, which is centered around intravenous formulations. These exciting developments have added a significant number of therapies in a previously limited treatment landscape.

Standardization of inpatient CPR status discussions and documentation within the Division of Hematology and Oncology at UPMC Shadyside Hospital.

147 Background: Medical professionals are trained to provide life-sustaining and cardiac resuscitation measures for admitted hospital patients. However, not all patients desire such aggressive measures. Lack of discussion and/or documentation about resuscitation preferences has led to care incongruous with patient’s wishes as previously documented or reported to providers or family members. In December 2016, 49% of adult patients admitted to the inpatient oncology service at UPMC Shadyside had a code status discussion documented prior to discharge. The aim of this project is to improve the quality and rates of CPR status conversations. Methods: A workgroup was formed in January 2017 among key stakeholders representing oncology physicians and fellows, palliative care faculty, oncology nursing, advance practice providers (APPs), and internal medicine house staff. A quality improvement (QI) proposal was developed and approved by the UPMC Quality Improvement Committee in February 2017. All oncology faculty, fellows, housestaff, and APPs were reminded weekly to complete CPR status conversations and documentation. APPs were formally trained by palliative care specialists to discuss and document CPR/code status with all admitted patients. Hospital leadership received a monthly update of CPR status documentation rates. Results: Since project implementation, CPR status assessment rates have improved from 49% to 80% as of June 2017, and an additional 714 patients had a CPR status discussed and documented compared to June 2016. Formal system-wide expectations are being developed by the CPR assessment workgroup that all admitted patients should have CPR/Code status discussions and documentation upon admission. Conclusions: Standardization of CPR status assessment with formal training of clinicians and APPs has resulted in a significant increase in the number of CPR status assessments on the inpatient setting. A formal CPR status assessment expectations document is in the process of being developed among the workgroup. Formal trainings by palliative care specialists for APPs are ongoing. Future trainings are planned for physicians, housestaff and fellows.

511P - The role of neuropeptide y in cancer-associated anorexia and its correlation with interleukin-1 beta

Background: Anorexia has been known as a factor that can increase mortality and morbidity in cancer patients. Anorexia in cancer patients can be triggered by the cytokines which produced by tumor cells and cells that involved in immunological response to the tumor. One of that cytokines is interleukin-1 Beta (IL-1β). Neuropeptide Y (NPY) is an extremely powerful orexigenic peptide that stimulates energy deficiency as a hunger center and proopiomelanocortin (POMC) is an anorexigenic peptide for satiety. Cytokines produced by tumor cells inhibit NPY in the orexigenic pathway and excite the POMC on the anorexigenic pathway caused anorexia. In cancer, the most important process causes anorexia is inhibition of NPY. Methods: This study is an observational analytic with a cross-sectional approach. The research was conducted at Dr. M. Djamil Hospital. The sample of this study was all patients with cancer-associated anorexia who were treated in the Hematology and Medical Oncology Division, Internal Medicine Department of Dr. M. Djamil Hospital. Sample is a patient who satisfies the inclusion criteria taken consecutively (n = 30). Results: This study found the average levels of NPY in patients with cancer-associated anorexia is 2.11 ± 0.76 pg/ml. It is significantly lower than normal limit (5-90 pg/ml) (p < 0.05). However, the average levels of IL-1β is 37.75 ± 16.86 pg/ml. It is significantly higher than normal limit (<3.9 pg/ml) (p < 0.05). The results of statistical analysis showed significant difference between the average levels of NPY on moderate anorexia patients and the average levels of NPY on severe anorexia patients (p < 0.05). There is also a significant correlation between increased IL-1β levels and decreased levels of NPY in patients with cancer-associated anorexia (p < 0.05 and r = -0.547). Conclusions: The result of the study concludes that there is a decrease the average levels of NPY and increase the average levels of IL-1β in patients with cancer-associated anorexia, and there is a negative correlation between the levels of IL-1β and NPY levels in patients with cancer-associated anorexia. Legal entity responsible for the study: Division of Hematology and Medical Oncology, Internal Medicine Department, Dr. M. Djamil General Hospital, Padang, Indonesia. Funding: None Disclosure: All authors have declared no conflicts of interest.

Combination treatment of ergosterol followed by amphotericin B induces necrotic cell death in human hepatocellular carcinoma cells.

The incidence of liver cancer, the second leading cause of cancer-related deaths has increased over the past few decades. Although recent treatments such as sorafenib are promising in patients with advanced hepatocellular carcinoma (HCC), the response rates remain poor thereby warranting the identification of novel therapeutic agents against liver cancer. Herein, we investigated the anti-cancer effect of ergosterol (a secondary metabolite in medicinal fungus) pretreatment followed by amphotericin B (AmB) treatment on liver cancer cell lines. We demonstrated that pretreatment with a nontoxic dose of ergosterol synergistically enhanced the cytotoxicity of AmB in both Hep3B and HepJ5 cells. The combination treatment-mediated suppression of cancer cell viability occurred through necrosis characterized by disrupted cell membrane and significant amounts of debris accumulation. In addition, we also observed a concomitant increase in reactive oxygen species (ROS) and LC3-II levels in HepJ5 cells treated with ergosterol and AmB. Our results suggest that ergosterol-AmB combination treatment effectively induced necrotic cell death in cancer cells, and deserves further evaluation for development as an anti-cancer agent.

A better angel of our nature: Hanna Michel "Jean" Khoury, MD (April 24, 1967-May 22, 2017).

A better angel of our nature: Hanna Michel "Jean" Khoury, MD (April 24, 1967-May 22, 2017).

A needs-based curriculum for hematology/oncology mid-level providers.

121 Background: Mid-level providers, both nurse practitioners and physician assistants have comprehensive clinical training, however, they do not undergo in depth sub-specialty training prior to working within a sub-specialty practice. In addition, at our institution, often they are not integrated into academic culture resulting in dissatisfaction with educational opportunities. As a result, we set out to develop a needs based curriculum in order to provide focused learning opportunities for our mid-level providers and improve their satisfaction with the educational environment. Methods: An initial survey was sent to all mid-level providers within the division of hematology and oncology at a single institution. The survey evaluated attendance to currently available lecture series, satisfaction with the educational environment, and an assessment on practitioner comfort level in managing 19 clinical conditions commonly seen in oncology patients. All responses were voluntary and anonymous. A lecture series was developed focusing on topics in which providers felt least comfortable. Follow up survey was to be conducted after 6 months and 1 year of the educational lecture series. Results: On average 11 providers attended each lecture. After 6 months of lectures, there was a suggestion that more practitioners were satisfied with educational opportunities at our institution (pre-intervention 0% (N = 15) satisfaction, at 6 months 43.75% (N = 7)). There was no suggested change in comfort level in managing the specific clinical conditions. Mid-level providers, in addition to attending the focused educational lecture series, were more likely to attend other educational lectures within the institution. Conclusions: At interim analysis, our educational intervention seems to have improved mid-level provider satisfaction with educational opportunities provided to them. In addition, there has been an unintended effect of improving their attendance at other lecture series offered, implying that they feel more integrated into the academic community. To date there is no suggestion that the curriculum is improving providers comfort level in managing the pre-defined clinical scenarios.

A hepatic fascioliasis case diagnosed after the treatment

Istanbul University, Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Hematology

Spotlight on romiplostim in the treatment of children with chronic immune thrombocytopenia: design, development, and potential place in therapy.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia. In approximately one-third of cases, the duration of thrombocytopenia will extend beyond 12 months consistent with a diagnosis of chronic ITP. Minor bleeding manifestations are common in chronic ITP while severe or life-threatening bleeding complications are uncommon. Moreover, spontaneous resolution occurs in the majority of children with chronic ITP necessitating treatment in only those children with ongoing bleeding manifestations or impairment in health-related quality of life (HRQOL). The characterization of thrombopoietin (TPO) and remarkable advancements in our understanding of the pathophysiology of ITP has led to the development of a new class of agents, the TPO-receptor agonists that have documented efficacy in the amelioration of thrombocytopenia and bleeding manifestations in chronic ITP. Romiplostim is a second-generation TPO-receptor agonist that has undergone limited evaluation in the treatment of chronic ITP in children. Evolving data suggest that romiplostim may be a safe and effective agent in the treatment of chronic ITP in children. Additional data are needed to confirm its ability to increase platelet counts, decrease bleeding manifestation, and improve the HRQOL of children and caregivers impacted by chronic ITP.

A guide to the anti-innovation “pharmaphobia” narrative for the aspiring innovator

Thomas P. Stossel is an American Cancer Society Professor of Medicine Emeritus at Harvard Medical School, Honorary Physician in the Hematology Division of Brigham & Women's Hospital, founding scientist of BioAegis Therapeutics, Visiting Scholar of The American Enterprise Institute and cofounder of Options for Children in Zambia.

Recent Advances in Multiple Myeloma

Oncology &amp; Hematology Review (US) are delighted to introduce our new Editor-in-Chief, Shaji K Kumar, consultant in the Division of Hematology at Mayo Clinic, and Professor of Medicine in the College of Medicine, Mayo Clinic, Rochester, Minnesota, US. In a recent interview, Dr Kumar discussed the latest advances in multiple myeloma, one of his major research interests.

Nilotinib As Second-Line Therapy in Patients with Chronic Myeloid Leukemia in Chronic Phase: Thailand Experience

Background: Nilotinib, a second generation tyrosine kinase inhibitor, was proved to have high efficacy on treatment of Philadelphia chromosome positive CML patients who failed or were intolerant to imatinib. Limited data was available on its efficacy and safety in Asian population.Methods: Chronic phase CML patients who have failure, suboptimal response or intolerance to imatinib according to ELN 2009 guideline were treated with nilotinib 400 mg twice daily on 7 centers in Thailand. Prospective data collection for 24 months was performed.Results: There were 106 cases participated in this study, 2 cases with initial T315I mutation were excluded from the study, total 104 cases were analysed. The median age was 46 (16-79) years with a slight male predominance over female at the ratio of 1.4:1 respectively. Twenty five percent received imatinib less than 12 months whilst 20% received imatinib longer than 60 months. The median duration of the prior imatinib treatment was 18 months (2-142 months). Best response to imatinib treatment were major molecular response (MMR) 5.8%, complete cytogenetic response (CCyR) 26%, major cytogenetic response (MCyR) 12.5%, complete hematologic response (CHR) 47%, and no CHR 8.7%. The reasons for nilotinib switching were imatinib failure 65%, imatinib intolerance 28%, imatinib suboptimal response 7%. Sixty-eight percent were completed 24 months follow up. Of those, 32% early discontinued treatment mostly because of unsatisfactory results or adverse events. Two patients died of infection and CNS bleeding during the study period.Evaluation were made every 3 months based on ELN 2009 criteria . Best response to nilotinib treatment included MMR 57%, CCyR 16%, MCyR 6%, CHR 16%, and no CHR 5%. At 3 months, 91%, 35%, and 14% of the patients CHR,CCyR, and MMR, respectively. Achieving CCyR or MMR at 3 months predicted a chance of achieving MMR (P= 0.00001) Those who did not achieve at least CHR at 3 months never achieved MMR, while 86 % of those who achieved CCyR at 3 months achieved MMR and 100% of those achieving MMR at 3 months had sustained MMR throughout the study period (24 months). Imatinib suboptimal response had significantly better outcome as compared to imatinib failure and imatinib intolerance group (P = 0.017). All of suboptimal response cases achieved CCyR , 86% achieved MMR, no early discontinue treatment in this group. While 75% of failure group achieved CCyR, 62% achieved MMR and 62% of intolerance group achieved CCyR, 38% achieved MMR. The reason for poorer response of intolerance group was high rate of early discontinue due to side effects, 17% vs 5% in the imatinib failure group.Initial BCR-ABL mutation analysis was performed on 90 cases, mutations were found on 16 cases, 2 of them were T315I which were excluded from the study. The cases with mutation significantly had poorer response to treatment than those without mutation (P = 0.001). There was one case with initial G250E mutation, who developed T315I mutation after treatment with nilotinib. At 24 months, 1 case progressed to accelerated phase and 3 cases progressed to blastic transformation. The 2-year progression-free survival and 2-year overall survival was 96% and 98%, respectively.Skin rash, musculoskeletal pain, and infection were the three most common non-hematologic adverse events found in 18%, 13%, and 6% of the patients, respectively; however, most of them were grade 1-2, except for 4 cases with grade 3-4 infections .Grade 3-4 hematologic adverse events included thrombocytopenia (12%), neutropenia (11%), anemia (5%), and leucopenia (4%); and most of them were manageable. Although biochemical abnormalities were commonly found, most of them were mild. Grade 3-4 events found were hypophosphatemia (6%), hyperglycemia (4%), and elevated serum lipase (4%). Only 10 cases (9%) permanently discontinued nilotinib due to its adverse effects.Conclusions: Nilotinib, as a second line treatment for Thai patients with chronic phase CML showed excellent efficacy and tolerability. Indication for nilotinib treatment, initial mutation status and depth of response at 3 months after treatment can predict outcomes of the patients.Author contact: KanchanaChansung M.D. Division of Hematology, Department of Medicine, Faculty of Medicine, Khonkaen University, Khonkaen, Thailande-mail: kchansung@gmail.com DisclosuresNo relevant conflicts of interest to declare.

Liver Dysfunction in Previously Untreated Chronic Lymphocytic Leukemia: Prevalence and Outcomes in a Large Cohort

INTRODUCTION: The prevalence of liver dysfunction in patients with previously untreated chronic lymphocytic leukemia (CLL) is unknown; knowledge of which may provide important context for emerging therapeutic options with possible hepatotoxicity. The impact of liver dysfunction on outcomes of CLL patients is not well described.METHODS: Between 09/1993 and 04/2016, previously untreated CLL patients seen in the Division of Hematology at Mayo Clinic at diagnosis (<12 months) and who had baseline assessment of at least one of the following liver function tests (LFTs): alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin were included in this analysis. Baseline lab values were defined as the closest value to CLL diagnosis for each lab within 12 months prior to diagnosis up through 6 months after CLL diagnosis. Patients with at least one abnormal LFT (defined as greater than 1.5 x the upper limit of normal) were classified as having liver dysfunction at diagnosis. Analysis for factors related to baseline liver function was performed using age- and sex-adjusted logistic regression models. Kaplan-Meier methods and multivariable Cox regression analysis was used to evaluate time to first treatment (TTFT) and overall survival (OS).RESULTS: Of 2336 previously untreated CLL patients who met the inclusion criteria, 123 (5%) patients had at least one abnormal LFT value at time of diagnosis. Thirty five patients had abnormal AST (median value 106 U/L, range 72-745 U/L, reference range 8-48 U/L), 25 patients had abnormal ALT (median 112 U/L, range 82-313 U/L, reference 7-55 U/L), and 54 patients had abnormal total bilirubin (median 2.10 mg/dL, range 1.8-26.5 mg/dL, reference range ≤ 1.2 mg/dL). Forty five patients had abnormal alkaline phosphatase; 35 patients in the year 2003 or later (median 198 U/L, range 172-2269 U/L, reference range 45-115 U/L) and 10 patients in 2002 or earlier (median 471.5 U/L, range 394-706 U/L, reference range 98-260 U/L).Abnormal LFTs were more common among those with advanced Rai stage disease (Rai 0-II=4.7% vs. Rai III-IV=13.4%; p<0.001) and among patients with lower hemoglobin (median 13.1 g/dL vs. 13.9 g/dL; p<0.001) at diagnosis. No difference in the rate of abnormal LFTs was observed based on cytogenetic abnormalities detected by FISH or CD38, CD49d, ZAP-70 or IGHV gene mutation status. There was no significant difference in prior alcohol abuse history between patients with liver dysfunction at diagnosis (6%) and those without (5%) (p=0.63). Similarly, there was no significant difference in body mass index between groups (median 27.8 vs. 27.8; p=0.12).After 12 years of follow-up, an estimated 69% of the cases with abnormal LFTs were treated. The most common type of treatments included anti-CD20 monoclonal antibody therapy only, followed by purine nucleoside based chemoimmunotherapy, and an alkylating agent with a monoclonal antibody. The median time to treatment was 4.3 years for cases with abnormal LFTs compared to 6.3 years for cases without abnormal LFTs (p=0.02). However, after adjusting for age, sex and Rai stage, there was no difference in TTFT among patients with abnormal LFTs at baseline compared to those with normal LFTs (hazard ratio [HR] = 1.2 (95% CI, 0.9-1.6); p=0.23).The median survival of CLL patients with abnormal LFTs at diagnosis was significantly shorter than those with normal LFTs (8.6 vs. 11.6 years, p<0.001, Figure 1). After adjusting for age, sex and Rai stage, multivariable cox regression analysis showed that abnormal LFTs retained independent prognostic significance for OS with a HR of 1.4 (95% CI, 1.1-1.8; p=0.012).CONCLUSION: At the time of CLL diagnosis, ~1 out of every 20 patients with previously untreated CLL has abnormal LFTs. These data provide context to the recent reports of hepatotoxicity with the use of signal inhibitors in untreated CLL. Although the presence of liver dysfunction at diagnosis does not seem to predict a shorter TTFT, the OS of these patients is significantly shorter compared to patients who have normal LFTs. [Display omitted] DisclosuresDing:Merck: Research Funding. Kenderian:Novartis: Patents & Royalties, Research Funding. Kay:Pharmacyclics: Research Funding; Tolero Pharmaceuticals: Research Funding; Acerta: Research Funding; Gilead: Membership on an entity’s Board of Directors or advisory committees; Morpho-Sys: Membership on an entity’s Board of Directors or advisory committees; Infinity Pharm: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees. Shanafelt:Janssen: Research Funding; Pharmacyclics: Research Funding; GlaxoSmithkKine: Research Funding; Genentech: Research Funding; Cephalon: Research Funding; Celgene: Research Funding; Hospira: Research Funding. Parikh:Pharmacyclics: Honoraria, Research Funding.

A Distributed International Patient Data Registry for Hairy Cell Leukemia

BACKGROUND: The study of rare diseases is limited by the uncommon nature of the conditions as well as the widely dispersed patient populations. Current rare disease registries such as the National Organization of Rare Diseases utilize centralized platforms for data collection; however because of their broad nature, these do not always capture unique, disease specific elements. Hairy Cell Leukemia (HCL) is a rare leukemia globally with approximately 900 new cases diagnosed in the US each year. The HCL Foundation undertook creation of a Patient Data Registry that collects data from multiple HCL Centers of Excellence (COE) around the globe to better understand the complications, treatment outcomes, disease subtypes, comorbid conditions, epidemiology, and quality of life of patients with HCL.METHODS: Investigators at The Ohio State University Department of Biomedical Informatics and Division of Hematology in collaboration with the HCL Foundation developed a Patient Data Registry (PDR) for the longitudinal capture of high quality research data. This system differs from other registries in that it uses a federated( rather than centralized) architecture, wherein data is queried and integrated in an on-demand manner from local registry databases at each participating site. Further, the data collected for use in the registry combines both automated exports from existing electronic health records (EHRs) as well as additional data entered via a set of web-based forms. All manually entered data comes from source documents, and data provenance spanning electronic and manually entered data is maintained via multiple technical measures. Patients may be enrolled at HCL COE, or, if they do not have access to a COE they may enroll via a web-based portal (www.hairycellleukemia.org). At this time due to regulatory requirements the web-based portal is available to US patients only. All data are de-identified (see Figure 1: De-Identification Workflow) which reduces regulatory burden and increases opportunities for data access and re-use. End users have access to data via a project-specific query portal.RESULTS: The Patient Data Registry has been deployed at The Ohio State University, Royal Marsden Hospital, and MD Anderson Cancer Center, and is undergoing deployment at the University of Rochester. Up to 25 international HCL COE may participate. In addition, US patients are actively entering the registry via the web-based portal. To date, 227 patients have been consented to the registry with 119 of these being via the web-based entry point.CONCLUSION: We created an international and web-based patient data registry which will enable researchers to study outcomes in HCL in ways not previously possible given the rarity of the disease.This work was made possible by research funding from the Hairy Cell Leukemia Foundation. [Display omitted] DisclosuresAndritsos:Hairy Cell Leukemia Foundation: Research Funding. Anghelina:Hairy Cell Leukemia Foundation: Research Funding. Lele:Hairy Cell Leukemia Foundation: Research Funding. Burger:Pharmacyclics: Research Funding. Delgado:Gilead: Consultancy, Honoraria; Novartis/GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Infinity: Research Funding. Jones:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lozanski:Beckman Coulter: Research Funding; Genentech: Research Funding; Stemline Therapeutics Inc.: Research Funding; Boehringer Ingelheim: Research Funding. Montserrat:Morphosys: Other: Expert Testimony; Vivia Biotech: Equity Ownership; Gilead: Consultancy, Other: Expert Testimony; Pharmacyclics: Consultancy; Janssen: Honoraria, Other: travel, accommodations, expenses. Parikh:Pharmacyclics: Honoraria, Research Funding. Park:Genentech/Roche: Research Funding; Amgen: Consultancy; Juno Therapeutics: Consultancy, Research Funding. Robak:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Tam:janssen: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Heckler:Hairy Cell Leukemia Foundation: Research Funding. Payne:Hairy Cell Leukemia Foundation: Research Funding.

Candida species isolated from different body sites and their antifungal susceptibility pattern: Cross-analysis of Candida albicans and Candida glabrata biofilms.

Candida species are regular commensal in humans, but-especially in immunocompromised patients-they represent opportunistic pathogens giving rise to systemic infection. The aim of the present work was to isolate and characterize for their antifungal profile Candida species from different body sites and to analyze the biofilms produced by C. albicans and C. glabrata isolates. Eighty-one strains of Candida species from 77 patients were identified. Epidemiological study showed that the most isolated species were C. albicans (44), C. glabrata (13) and C. parapsilosis (13) mainly from Hematology, Infectious Diseases, Medicine, Neonatology and Oncology Divisions, the majority of the biological samples were swabs (44) and blood cultures (16). The analysis of the biofilm formation was performed at 24 and 48-hours comparing resistant and susceptible strains of C. albicans to resistant and susceptible strains of C. glabrata. Candida albicans has a greater ability to form biofilm compared to C. glabrata, both in the susceptible and resistant strains reaching maturity after 24 hours with a complex structure composed of blastospores, pseudohyphae, and hyphae embedded in a matrix. On the contrary, C. glabrata biofilm was composed exclusively of blastospores that in the resistant strain, after 24 hours, were organized in a compact multilayer different to the discontinuous structure observed in the susceptible analyzed strains. In conclusion, the increasing of the incidence of Candida species infection together with their emerging drug resistance also related to the biofilm forming capability underline the need to monitor their distribution and susceptibility patterns for improving the surveillance and for a correct management of the infection.