bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Dose Steroids Can Alleviate Blinatumomab-Associated Toxicities without Negatively Impacting Treatment Efficacy
Authors: Mori Shahram , Nelson Rebecca Jean , Patel Rushang D. , Ahmed Wesam B. 
Published: October 2019

Abstract
Relapsed/refractory precursor B cell acute lymphoblastic leukemia (B cell ALL) carries a poor prognosis in adults and remains a challenging therapeutic area. Allogeneic stem cell transplantation is the only potentially therapeutic strategy for this group of patients, but its success depends on the disease status at the time of transplant. Blinatumomab is a recently approved bi-specific CD19-directed CD3 T-cell engager (BiTE) antibody in B-cell ALL patients who have failed induction chemotherapy. Its administration however is commonly complicated by grade III-IV toxicities including high-grade fevers and Cytokine Release Syndrome (CRS) defined as elevations in ferritin levels, pro-inflammatory cytokines such as IL-6, fever, chills and vascular leak. These complications can result in in premature treatment interruptions, failures as well as treatment-related mortality. At this time, it is unknown whether the concomitant use of steroids with Blinatumomab can alleviate these symptoms without negatively impacting the efficacy of treatment.
Here we describe two patients who were treated with standard dosing of Blinatumomab starting at 9 mcg/day on days 1-7 and 28 mcg/day on days 8-28. Both patients developed grade III-IV febrile episodes within the first 24 hours of treatment resulting in initial treatment interruption. These febrile episodes were associated with elevations in ferritin level. After a brief supportive measure, Blinatumomab was restarted but this time concurrently with methyl-prednisolone 5-10mg BID for days 2-5. Neither patient required any further treatment interruption or developed CRS as measured by normal IL-6 levels. In both cases a complete remission was achieved and they were successfully bridged to allogeneic stem cell transplantation.
In conclusion, in relapsed and refractory B-cell ALL, Blinatumomab-associated grade III/IV toxicities may be successfully addressed with low dose steroids without inhibiting anti-leukemic effect of BiTE antibody.

Disclosures
No relevant conflicts of interest to declare.
Cytotoxicity of the Recombinant Human Arginase (BCT-100) Against Acute Lymphoblastic Leukaemia (ALL)
Authors: Mussai Francis J , Booth Sarah , Vardon Ashley , Ng Margaret , Cheng Paul , De Santo Carmela 
Published: October 2019

Abstract
Acute Lymphoblastic Leukaemia (ALL) is the most common leukaemia of childhood. Despite improvements in overall survival, significant numbers of children die from relapsed/ refractory disease or suffer the morbidities of multi-agent chemotherapy regimens. A major challenge is to find new drugs which are active against ALL blasts or which make blasts more sensitive to existing chemotherapy, without adding to toxicity. Arginine, is a semi-essential amino acid, required for protein synthesis, and cell viability. Some cancers are dependent on arginine for proliferation and survival - 'arginine auxotrophism'. We have recently identified that arginine metabolism plays a key role in AML pathogenesis and can be therapeutically targeted. Therefore we investigated if Acute Lymphoblastic Leukaemia is also sensitive to therapeutic arginine depletion.
A clinical grade, FDA approved, pegylated-recombinant human arginase, PEG-rhArgI molecule BCT-100, has been developed by Bio-Cancer Treatment International (BCT, Hong Kong).A Phase I and II clinical trial has been successfully completed in adult hepatocellular carcinoma. The Phase I trial demonstrated that at 1600U/kg BCT-100 (Observed Biological Dose), plasma arginine falls below 8mM (Adequate Arginine Depletion - ADD) and is maintained for up to 166 hours, with no evidence for neutralising immunogenicity. Only grade 1 or 2 reversible transaminitis was seen and patients experienced significant improvements in overall survival.
Arginine is recycled by cells from ornithine, through the enzymes OTC and ASS. These enzymes have been identified as biomarkers of sensitivity to arginine depletion in solid tumours. ASS and OTC expression pattern was characterised in leukaemic blasts from 37 ALL patients (19 adult, 18 paediatric), revealing the majority of ALL cases are deficient in one or more of these enzymes (Adults: ASS-: 84% OTC: 53%; Paediatric: ASS- 44% OTC 27%). Thus the majority of ALL blasts are auxotrophic for arginine.
We tested the cytotoxicity of BCT-100 against ALL. We demonstrated that ALL cell lines (n=4) are dependent on arginine for proliferation and survival. In vitro, BCT-100 leads to a complete depletion of extracellular arginine and induction of autophagy. BCT-100 was tested against primary blasts from ALL patients - IC50S ranged from 17.5-2400ng/ml. Sensitivity to BCT-100 did not correlate with clinical or cytogenetic characteristics. The study is the first report on the arginine dependence of adult and paediatric ALL and provides the rationale for ongoing translation of BCT-100 for patients with relapsed ALL.

Disclosures
No relevant conflicts of interest to declare.
Correlation of PET Scan Negativity and Higher Absolute Lymphocytes: Monocytes (ALC:AMC) Ratio As Prognostic Markers in Classical Hodgkin Lymphoma Patients Treated with ABVD Chemothearapy at a Single Center in Saudi Arabia
Authors: Motabi Ibraheem H , Zaidi Syed Ziauddin A. , Iqbal Shahid , Gill Atta Munawar , Tailor Imran Khan , Alshehry Nawal Faiez , Elghazaly Assem A , Almudaibigh Samer Homoud S , AlGhamdi Mubarak S. , Murtaza Ghulam , Butt Ahmed 
Published: October 2019

Abstract
The International Prognostic Score (IPS) is the standard stratification system for survival in patients with classical Hodgkin's lymphoma (cHL). However, the IPS only applies to patients with advanced stage disease and it does not offer risk stratification for classical Hodgkin's lymphoma patients diagnosed with limited disease [i.e., stages I and IIA, without constitutional symptoms and no bulky disease. Furthermore, early interim positron emission tomography (PET) has been shown to have a prognostic value superior to that of the IPS in patients with advanced-stage cHL in an analysis (Gallamini et al).
Lymphopenia (<600/ul), monocytosis >750 per ul (Tadmore et al) and high tumor-associated macrophages (TAM) are reported to be negative prognostic factors for survival in classical Hodgkin's lymphoma (Koh et al). More recent studies suggested a prognostic role for the peripheral blood absolute lymphocyte count/absolute monocyte count (ALC/AMC) ratio at diagnosis in cHL patients treated with multitude of chemotherapies (Porrata et al, Tadmor et al). It is intriguing to investigate the significance of the ALC/AMC ratio in relation to PET negativity after treatment.
Out of 164 cases of cHL treated at our center with ABVD +/- radiation therapy, we identified 70 patients who were evaluated by PET Scan. Median age was 26 years (range 14-80), 33 (47%) were stage IV, Median IPS was 3 (range1-6). We tested correlation of a high ALC/AMC ratio (>2.1) with achievement of a negative PET scan after ABVD chemotherapy. We arbitrarily chose cut-off value of >2.1 (Tadmore et al) from the multiple values reported recently, as this multicenter study had the largest number of patients.
A total of 45 patients achieved a negative PET scan. Mean ALC/AMC ratio was 2.39 (range0.19-14.6). ALC/AMC ratio of >2.1 did show a trend for better OS in addition to a negative PET scan. A Spearman correlation test of a negative PET result showed a positive correlation with ALC/AMC ratio of >2.1 though it was weak.
This study suggests that the ALC/AMC ratio may be a simple, inexpensive, and independent prognostic factor in cHL outcome and may have a role in the stratification of cHL patients in addition to the International Prognostic Score, TAM content and acheivement of a negative PET scan early post chemotherapy. However we plan to define our own best cut off value for ALC/AMC ratio by ROC and AUC analysis as ALC/AMC Ratio of ≥2.1 did not discriminate survival advantage very well and it may be a reason for weaker correlation with likelihood of a negative PET.
Further larger studies are needed to confirm our findings.

Disclosures
No relevant conflicts of interest to declare.
Extracorporeal Photopheresis for the Treatment of Mycosis Fungoides
Authors: Atilla Erden , Ataca Pinar , Civriz Bozdag Sinem , Toprak Selami Kocak , Yuksel Meltem Kurt , Akay Bengu Nisa , Sanli Hatice , Topcuoglu Pervin , Ozcan Muhit , Gurman Gunhan , Ilhan Osman 
Published: October 2019

Abstract
Backround: The treatment of mycosis fungoides (MF) is determined by disease extent, prognostic factors and patient characteristics. Extracorporeal Photopheresis (ECP) was approved by the US Food and Drug Administiration for the palliative treatment of mycosis fungoides since 1988. Herein, we present our MF patients who have received ECP.
Patients and Methods: We retrospectively included 50 MF patients who have diagnosed at our center. ECP was given empirically in cycles of 2 consecutive days in every 2 to 4 weeks at any time during their follow-up.
Results: The patient characteristics is shown in table. Previous lines of treatments were; topical retinoids (bexarotene), topical corticosteroids, phototherapy (PUVA), Narrowband ultraviolet B light (NBUVB), Interferons, Metotrexate (MTX), CHOP (cyclophosphamide, daunorubicin, vincristine, prednisolone). ECP is combined with gemcitabine, PUVA, MTX, Bexaroten, IFN or Vorinostat. The overall response rate (ORR) was 54% with 30% complete response rate (CRR). 10/15 complete responders (67%) had stage 3-4 disease at diagnosis and 7/15 (47%) had received ≥ 3 lines of treatment prior to ECP. 18 patients (36%) had progressive disease after ECP while 3 patients (6%) were refractory and underwent allogeneic stem cell transplantation. The few adverse events of ECP included in 8 patients (16%) as catheter-related infection, headache, fever, chills and nausea. The OS was 68 months.
Conclusion: ECP is a favorable treatment option for suitable patients in MF with high ORR and low risk of adverse events.
Presenter has relevant financial relationship(s) to disclose: No.

Disclosures
No relevant conflicts of interest to declare.
Clinical Features and Treatment Outcomes of Angioimmunoblastic T-Cell Lymphoma: An Analysis from a Nationwide Multicenter Registry, Thailand
Authors: Sirijerachai Chittima , Chansung Kanchana , Lekhakula Arnuparp , Julamanee Jakrawadee , Wudhikarn Kitsada , Bunworasate Udomsak , Norasetthada Lalita , Nawarawong Weerasak , Khuhapinant Archrob , Ekwattanakit Supachai , Numbenjapon Tontanai , Prayongratana Kannadit , Chuncharunee Suporn , Niparuck Pimjai , Suwanban Tawatchai , Kanitsap Nonglak , Wongkhantee Somchai , Wong Peerapon , Makruasi Nisa , Intragumtornchai Tanin 
Published: October 2019

Abstract
OBJECTIVES: To analyze clinical features, treatment outcomes in Thai patients with angioimmunoblastic T cell lymphoma (AITL).
PATIENTS AND METHODS: From a nationwide multicenter registry of 4,056 NHL patients in Thailand between 2007 and 2014, there were a total of 54 angioimmunoblastic T cell lymphoma (AITL) patients. The clinical features and treatment outcomes were analyzed.
RESULTS: There were a total of 54 cases accounted to the prevalence of 1.2 % of NHL and 12% of peripheral T cell lymphoma. The median age was 59 years (range 35-81). Male: female was 1.5:1. Seventy-eight percent of patients had advanced disease (stage III, IV), 69% had B symptoms, 28% had poor performance status (ECOG > 2) and 61% had elevated serum LDH level. Extranodal involvement was 56 %; the most common sites of which were bone marrow (30%) and liver (19 %). Thirty-five percent of the patients had IPI score > 2 and 7% had PIT >2. Eighty-one percent of patients were treated with chemotherapy of which CHOP/CHOP-like was the main regimen. Of the 43 evaluable patients receiving chemotherapy, complete remission was achieved in 41.9%. Forty-four percent of patients with complete remission had disease progression. With the median follow-up time of 65 months, the 5-year overall survival was comparable to peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), (28% vs. 37%, p=0.7). On multivariate analysis, response to treatment (at least PR) was associated with better outcome (HR 0.13, 95%CI 0.05-0.33, p= 0.000). Patients with PIT > 2 or B symptoms trended to have inferior survival outcome, although statistical significant was not achieve (HR 3.2, 95%CI 0.36-27.95, p=0.3; HR 2.3, 95%CI 0.78-7.31, p=0.13).
CONCLUSIONS: The prevalence of Thai patients with AITL was much less than data reported from the international T-cell lymphoma project (18% of T-NHLs) (Vose et al, JCO2008;26:4124-30). The long-term survival was not inferior to patients with PTCL, NOS.

Disclosures
Khuhapinant: Roche: Honoraria.
Mir-217 Reverses the TKI Drug-Resistance of K562 Cells By the Downregulation of Heme Oxygenase-1
Authors: Wang Jishi , Wang Chanjuan , Ma Dan , Fang Qin , Ren Mei 
Published: October 2019

Abstract
Upregulation of Heme oxygenase-1 (HO-1) strengthens drug-resistance to apoptotic death in the several kinds of cancer cells. Our recent study shows the higher levels of HO-1 expression in the thyrosine kinase inhibitors (TKI) resistance K562 cell line and cells from Imatinb-insensitive CML patients. The cause of HO-1 upregulating, though, is still unclear yet.
MicroRNAs (miRNAs) play a significant role in the pathogenesis of cancer. They also are known as potential biomarkers and therapeutic targets. In the hematological neoplasm, miRNAs take part in not only cancer development, but also drug resistance. However, the problem has not been solved yet is how the microRNA involved in.
This study found that the expression level of microRNAs were much different depended on if it is Imatinb-insensitive or not. The phenomenon was observed both in the K562 and CML patients. The mir217 was one of these microRNAs that significantly deceased when the K562 had been induced to resist the Imatinb. Meanwhile,TKI-resistance K562 cells can be in association with an increase in levels of HO-1 and a decrease in levels of miR-217. In the TKI-resistant K562 cells, the decreased of miR-217 upregulated the expression of HO-1 through a 3'-untranslated region(UTR) of HO-1 and induced the resistance against TKI. Interestingly, TKI-resistant K562 cells exposed to miR-217 mimic can partially make the cells be sensitized to TKI again in association with upregulation of miR-217 and downregulation of HO-1 in vitro. The IC50 of the TKI-resistant K562 cells exposed in 7.5uM Imatinb for 48 hours also decreased after transfecting miR-217 mimic for 48 hours.
In our on-going experiment, the express level and interaction of HO-1 and miR-217 will be tested in K562 tumors growing in immune-deficient mice that were treated with the combination of mir-217 inhibitor, expression HO-1 virus and TKI. The express of HO-1 and miR-217 also will be examined in the TKI-insensitive CML patients and the mir217 and HO-1 regulated mechanism will be investigated in vivo.
According to our results, the reversibility of the mir-217 downregulating Heme oxygenase-1 in the K562 cells with TKI drug tolerance likely provides a potentially exciting miRNA therapeutic strategy.
MiRNAs therapy could be utilized as a powerful therapy which would focus to the drug-resistance patients. Drug-resistance cancer cells may be sensitized to former conventional or targeted chemotherapy.

Disclosures
No relevant conflicts of interest to declare.
High Prevalence of Peripheral Artery Occlusive Disease (PAOD) Among Patients with Chronic Myeloid Leukemia (CML) Receiving Tyrosine Kinase Inhibitors (TKIs): A Cross-Sectional Study
Authors: Rattanathammethee Thanawat , Tantiworawit Adisak , Rattarittamrong Ekarat , Chai-Adisaksopha Chatree , Hantrakool Sasinee , Phrommintikul Arintaya , Gunaparn Siriluck , Norasetthada Lalita 
Published: October 2019

Abstract

Background: Although TKIs become the standard of care in CML, the long-term complication has not been well recognized. There were reports of nilotinib associated metabolic derangements including diabetes and PAOD while these complications in other TKIs have not been well recognized.
Objectives: To compare the prevalence of PAOD among CML patients and matched-control population.
Methods: A cross-sectional case control study was conducted among CML patients receiving TKIs at Chiang Mai University Hospital between February to December 2014. The control group was matched by age, sex and diabetes. Screening PAOD using Fukuda VS-1500 to measure ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI) for arterial stiffness were performed in both groups. The cutoff value of pathologic ABI and CAVI were less than 0.9 and higher than 8, respectively.
Results: Seventy-eight CML patients and 156 matched-control population(1:2 ratio) were included. For CML patients, the median age was 55 years (21-86). Atherosclerotic risks including hypertension(20.5%), diabetes(12.8%), dyslipidemia(26.9%), metabolic syndrome(19.2%) and smoking(2.6%). Sixty-one patients(78.2%) were on imatinib, all as first-line, 13 patients(16.7%) on nilotinib (7.7%first-line, 92.3%second-line) while 4 patients(5.2%) were on dasatinib(all third-line). Median duration of imatinib, nilotinib and dasatinib treatment were 89.6, 46.7 and 22.1 months, respectively. The prevalence of pathologic ABI and CAVI were 9.0% and 26.7%, respectively. Patients receiving nilotinib had highest prevalence of abnormal ABI of 30.7% while patients receiving imatinib and dasatinib had abnormal ABI of 5% and 0%, respectively (p=0.004). Abnormal arterial stiffness by CAVI in nilotinib users were 15.4% compared to 27.8% and 50% in imatinib and dasatinib (p=0.815). Patients with CML had higher prevalence of pathologic ABI than in control group with an odds ratio(OR) of 2.09(95%CI 0.71-6.21, p=0.181). The only factor independently associated with pathologic ABI was level of HbA1C over 7 g/dl [OR2.41(95%CI 1.11-5.25; p=0.026)]. Age over 60 years [OR 3.95(95%CI 1.22-12.73, p=0.022)] and fasting plasma glucose over 126 mg/dl [OR 7.96(95%CI 1.21-52.26, p=0.031)] were independently associated with pathologic CAVI.
Conclusions: The prevalence of PAOD by using ABI was higher among CML patients than in control population. CML patients receiving TKIs who have diabetes and older than 60 years old have a higher chance of developing PAOD and should be carefully monitored.

Disclosures
No relevant conflicts of interest to declare.
Oncoguide System- a Computerized Interactive Assistance System for the Diagnosis and Treatment of CML / MPN and MDS
Authors: Hempel Dirk 
Published: October 2019

The project aims to develop and implement a computerized interactive assistance system for the diagnosis and treatment of CML / MPN and MDS. The system is based on modulated, established medical guidelines with reference to the individual patient information. The user is navigated through the complex recommendations of current guidelines and decision trees of the CML/MPN and MDS, similarly to a car navigation system.
The system was developed in cooperation between the Steinbeis Institute for Clinical haematooncology and the Fraunhofer IOSB in Karlsruhe. In addition to the guidelines, recommendations on current evidence-based research results will be incorporated into the expert system. The medical user is hereby offered a systematic decision support. In addition, the decisions are documented and visualized in an intuitive user interface. The expert system is also able to point to currently recruiting therapy studies. The future system is planned to be self-learning by weighing the decision criteria. It will adjust the decision criteria by increasing usage and possibly readjusted criteria.
Technical implementation and advantages of this solution:
From a technical perspective, the knowledge-based system should be implemented as a client-server architecture. The server acts as a central data storage, for example, in the form of a database. As a client, for example, Internet browsers can be used. So it is possible to centrally reproach the accumulated knowledge and to present the current results to each user. The advantage of such a technical solution compared to guidelines-books is rapidly adaptable knowledge on new research results, as well as the implementation of a self-learning system. The system design has to pay particular attention to an intuitive user interface. On the server's side, the knowledge of guidelines and interviews with experts have to be formalized in an appropriate manner. There are approaches based on an ontological or logic-based modeling.
On the client's, side the system suggests the user appropriate decision for the diagnosis and further treatment of diseases. The underlying methodology is based on approaches from artificial intelligence, such as the Bayesian inference or machine learning methods.

Disclosures
Hempel: Novartis and Celgene: Research Funding.
Bortezomib-High Dose Melphalan Conditioning for the Treatment of MM Patients Undergoing ASCT
Authors: Jimenez-Zepeda Victor , Duggan Peter , Neri Paola , Chaudhry Ahsan , Tay Jason , Luider Joanne , Bahlis Nizar J. 
Published: October 2019

Abstract
Introduction Recent data suggests that bortezomib, a proteasome inhibitor, in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve the level of response for MM patients undergoing auto-SCT. In the present study, patients receiving induction followed by ASCT with Bor-HDM and HDM alone were evaluated. Methods All consecutive patients undergoing ASCT from 01/2004 to 03/2016 were evaluated. All patients received induction chemotherapy before undergoing auto-SCT. Patients received conditioning with either HDM at 200 mg/m2 (or adjusted as per renal failure) or HDM with Bortezomib (Bor-HDM). Most of patients received Bortezomib conditioning at 1.3 mg/m2. As per physician discretion, the dose of 1 mg/m2 was also employed in 30% of cases. Definitions of response and progression were used according to the EBMT modified criteria. MRD negativity was assessed by flow cytometry at day-100 post-ASCT. Results Clinical characteristics are shown in Table 1. Among 301 cases, 129 were treated with Bor-HDM while 172 patients went onto receive HDM alone as part of the conditioning regimen. Induction regimens are shown in Table 1. At the time of analysis, 83% and 58% of patients in the Bor-HDM and HDM group are still alive and 34% and 69.1% of patients have already progressed, respectively. At day-100 post ASCT, ORR of 97%, with CR/VGPR rate of 84.2% was seen in the Bor-HDM group compared to 94.2% and 68.6% in the HDM group (p=0.001). MRD negativity was higher in the Bor-HDM group (33.3%) compared to HDM (12.2%) (p=0.001). Median OS was similar for Bor-HDM and HDM (p=0.864) (Fig 1a). In addition, median PFS did not differ among patients receiving HDM or Bor-HDM (37.7months vs 29.3 months, p=0.2) (Fig1b) In conclusion,Bor-HDMis a conditioning regimen able to provide higher rates ofnCR/CR, as well as MRD negativity compared to HDM alone. Further studies are warranted to explore this regimen, especially when other upfront therapies are employed.
Overall Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Overall Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Figure 1 Progression-Free Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Figure 1. Progression-Free Survival according to the conditioning regimen employed for patients with MM undergoing ASCT

Disclosures
Jimenez-Zepeda: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Onyx: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria; BMS: Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau.