Successful Mobilization Research Articles

Trapezium Fracture: Case Report

ABSTRACT Background: Trapezium fractures are extremely uncommon, accounting for only 4% of all hand injuries. Trapezium fractures are a very infrequent kind of carpal bone injury. They can happen alone or in conjunction with another carpal bone lesion. Cases report: A 19-years old female right hand dominant with no medical conditions presented to the Emergency Department at East Jeddah Hospital as a case of motor vehicle accident (MVA). She was sitting in the back chair where she put her both hands in hyperextension over the seat in front to protect her during the injury. She came complaining of left hand pain and swelling. Conclusion: We report this case of trapezium fracture, which is a rare injury with our management done by using open reduction and Herbert’s screws fixation. The patient got successful early mobilization. We achieved good clinical and functional outcomes as well as satisfaction.

Building a culture of early mobilization in the pediatric intensive care unit-a nuts and bolts approach.

The culture of sedation and immobilization in the pediatric intensive care unit (PICU) is associated with PICU-acquired weakness, delirium, and poor functional, neurocognitive and psychosocial outcomes. A structured approach to introducing physical activity, as early as possible after PICU admission, may prevent these complications and optimize the holistic outcomes of critically ill children. Changing culture and introducing new clinical practice in PICU is complex, but can be approached systematically, using a “nuts and bolts” approach targeting the basic, practical considerations and essential required elements or components. Extending the construction analogy, this article reviews the relevant literature to describe the essential elements required to build and sustain a successful and safe early mobility program in the PICU. Effective early mobilization requires individual patient assessment and goal setting, using a collaborative inter-disciplinary, patient- and family-centered approach, to ensure mobility goals and physical activities are appropriate for the patient’s age, condition/s, premorbid function, strength, endurance and developmental level. Early mobility activities for the pediatric age spectrum include active or active-assisted range of motion exercises, neurodevelopmental play, use of mobility devices, in-bed exercises, transfers, sitting or standing tolerance, crawling, pre-gait activities, ambulation and activities of daily living, with a focus on play as function. Although there are few complete contraindications to early mobilization, appropriate precautions and preparation should be taken to mitigate potential safety concerns. Although there are many perceived barriers to early mobilization in the PICU, at the level of patient, provider, institution and knowledge translation; these are not objectively associated with increased risk during mobilization and can be overcome through an engaged process of practice change by all members of the interprofessional clinical team. Early mobility programs could be initiated in PICU as systematic quality improvement initiatives, with established processes to optimize structural, process and system elements and to provide continual feedback, measurement, benchmarking and collaboration; to ultimately impact on measurable patient outcomes. Early, graded, and individually prescribed mobilization should be considered as part of the standard PICU “package of care” for all critically ill and injured children, in order to improve their functional status and quality of life after PICU discharge.

Combination brentuximab vedotin and bendamustine for pediatric patients with relapsed/refractory Hodgkin lymphoma

AbstractIn patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL), achieving a complete metabolic response (CMR) after salvage therapy is associated with superior outcomes, and optimal treatments must be identified. The combination of brentuximab vedotin and bendamustine (BVB), although highly active in adult patients, has not been extensively evaluated in pediatric patients with R/R HL. We performed a multicenter, retrospective review of pediatric patients <21 years of age with R/R HL treated with BVB from January 2016 through July 2019. Response was assessed by local radiologists according to Lugano classification criteria. Twenty-nine patients (17 relapsed, 12 refractory) with a median age of 16 years (range, 10-20) were treated with BVB and received a median of 3 cycles of therapy (range, 2-7). Patients received an infusion of 1.8 mg/kg of BV on day 1 with bendamustine 90 mg/m2 on days 1 and 2 of 3-week cycles. Nineteen patients (66%) achieved a CMR (95% CI, 46-82). An objective response was observed in 23 patients (objective response rate, 79%; 95% CI, 60-92). The most common grade 3 and 4 toxicities were hematologic, and 3 patients (10%) experienced grade 3 infusion reactions. Seventeen of 18 patients underwent successful mobilization and collection of stem cells. Sixteen patients (13 autologous, 3 allogeneic) received a consolidative transplant after BVB. The 3-year post-BVB event-free and overall survival were 65% (95% CI, 46-85) and 89% (95% CI, 74-100), respectively. For pediatric patients with R/R HL, BVB was well tolerated and compared favorably with currently accepted salvage regimens.

Multidisciplinary, early mobility approach to enhance functional independence in patients admitted to a cardiothoracic intensive care unit: a quality improvement programme

Early mobilisation following cardiac surgery is vital for improved patient outcomes, as it has a positive effect on a patient’s physical and psychological recovery following surgery. We observed that patients...

Home State Oriented Diaspora Organizations and the Making of Partisan Citizens Abroad: Motivations, Discursive Frames, and Actions Towards Co-Opting the Turkish Diaspora in Europe

What motivates diasporas to support undemocratic rule in their countries of origin while enjoying democratic freedoms in their countries of settlement? This study adopts a meso-level approach to answer this question, and focuses on the Turkish diaspora in Europe as a case study. Lately, the diaspora governance literature has focused on official diaspora institutions and the policies of countries of origin. This study, alternatively, highlights “diasporic civic space” as an arena entrenching authoritarian practices “at home.” It investigates the conditions under which diasporic civic space can be co-opted by undemocratic countries of origin and the role of “home state oriented diaspora organizations” in this process of co-optation. The study shows that diasporic civic space can offer resources to undemocratic regimes to mobilize previously dormant diaspora communities and create a support base abroad that is driven by nationalism and partisanship. The empirical discussion unveils four factors behind the successful mobilization of diasporas by undemocratic countries of origin: (1) nationalist sentiments among the diaspora; (2) motivations to get a share from the perks that may be meted out by home country government; (3) feelings of insecurity, fear, and marginalization as immigrants; and (4) the desire to assert one’s identity and cultural ties vis-à-vis the majority in countries of settlement. The findings are based on the case of the Turkish diasporic civic space in Europe, which has recently been mobilized by a diaspora organization with political ties to the Justice and Development Party (AKP). Original data are drawn from semi-structured interviews conducted in 2018–2019 with members and representatives of major pro-AKP diaspora organization known as the Union of International Democrats (UID), as well as Alevi, Kurdish, and Islamist/conservative diaspora organizations in Sweden, Austria, Bosnia and Herzegovina, and Germany. The findings contribute to the understanding of undemocratic home states’ non-coercive and de-territorialized governance practices beyond their borders.

From Archangels to Virtual Pilgrims: A Brief History of Papal Digital Mobilization as Soft Power

The perpetual public display of successful mass mobilization and pilgrimage has become a pillar of papal soft power. During the 20th century, the papacy had repeatedly demonstrated its ability to use new technologies for public communication, media content production and mass mobilization. John Paul II endorsed the establishment of the first Vatican website and an official papal e-mail account, which provided Catholics a new form of communication with the Holy Father. During the pontificate of Benedict XVI, the papacy created several Twitter accounts, which would become the backbone of papal digital mobilization. Francis built on the success of his predecessors as he initiated the modernization of the Holy See’s media department. However, with the growth of the Internet and the stress test of the COVID-19 pandemic, the mechanics of mobilization, pilgrimage and power have considerably changed. With the religious role of the popes taken as a given, the paper looks into the history of papal mobilization, the role of the Internet and why it is not used to its full potential yet.

Challenging oppression: how grassroots anti-racism in Berlin breaks borders

ABSTRACT In recent years, the successful anti-migrant mobilization of populist radical right parties and movements in Germany has stimulated the anti-racist struggle. This article investigates the anti-racism of grassroots organizations that contest border regimes in Berlin. While grassroots anti-racism also intends to combat the ideology of populist radical right parties, it contributes distinctively to the debates on racism, colonialism and border regimes. Specifically, grassroots anti-racism sheds light on the mechanisms through which border regimes oppress and racialize migrants. Crucially, by acknowledging the imbrication between historical racial inequalities and border regimes, grassroots organizations weave an anti-racist struggle against border regimes that is emancipatory for racialized migrants. I contend that grassroots anti-racism contributes to tackling the pervasive historical amnesia (Hall, S. 2000. “Conclusion: The Multi-cultural Question.” In Un/settled Multiculturalisms: Diasporas, Entanglements, ‘Transruptions’, edited by B. Hesse. Zed Books) regarding colonialism and the role of racism in the construction of the German nation.

Adapting to the “new normal” post-pandemic consumer behavior: the case of Rafeeg’s strategy of service marketing

Learning outcomes After reading the case study, the students will be able to analyze the impact of post-pandemic “new normal” customer behavioral change on a start-up aggregator operating virtually. Recognize the need for the service marketing strategy to prepare a service provider/aggregator to sustain a dynamic and volatile consumer environment. Understand the importance of competitors’ analysis as a primary step of service marketing strategy in influencing “new normal” consumer behavior. Examine the utility of customer engagement through website blogs, social media posts, videos and continuously updated information on the mobile application in influencing the “new normal” customer behavior, from skinner operant conditioning behavior and Rusbolt’s investment model perspectives. Case overview/synopsis Rafeeg is a mobile application-based home maintenance service providing company, conceived and founded in 2017 by Khamis Alsheryani – who, as an Emirati entrepreneur, has a prior record of accomplishing successful mobile applications and business ventures since 2004. The unique selling proposition of Rafeeg in the Abu Dhabi market is its functioning as the home maintenance services aggregator bringing its suppliers and consumers under-one-roof alongside maintaining ensuring high quality, punctuality and security at competitive prices. Rafeeg has collaborated with approximately 1,000 licensed suppliers using nearly 5,000 technicians and maintenance workers with a customer base of about 70,000 households. Although it is formally situated in Al Salam St, Abu Dhabi, United Arab Emirates (UAE), the company communicates with its consumers virtually. However, with the outbreak of the COVID-19 pandemic in the UAE in March 2020, Rafeeg witnessed a considerable decrease in service requests. Consumers’ psychological fear of the pandemics spread into their houses through the technicians and maintenance workers and the degree of hygienic practices the latter follows before their service provision acted as the major reason behind the fall in requests. Despite Alsheryani’s assurance on the provision of only those suppliers who are verified of their hygienic practices, negative COVID-19 test reports and their availability to the consumers as proof and regular temperature checks of the technicians, the consumer apprehensions remained stagnant and the loss of new service requests, as well as revenue, continued. The pandemic’s spread and consequent lockdown of services in the UAE affected Rafeeg’s business operations gravely, as projected by its sudden drop-in service requests – from 53,638 average monthly customer requests in January and February to approximately 10,000 in March and April. The sudden drop of 81% in new requests drove Alsheryani to develop a service marketing strategy in May to boost consumer behavior, encouraging them to resume their requests without further apprehensions. However, with the continuous rise in the pandemic and vaccines still under trial and research, Alsheryani contemplates the viability of the new marketing strategy. Alsheryani took measures in supplier training programs, excommunicating with suppliers who fail to comply with his strict safety regulations, developing the app with clearly stated, uniform, safety procedures and bearing the additional safety-related costs small suppliers provide quality work as part of the strategy. Despite so, will there be an increase in new requests? Will the bearing of additional costs on the suppliers’ behalf jeopardize its competitive advantage in UAE? Should he consider an alternate business model to adapt to the new normal environment? Complexity academic level This case is written for undergraduate students majoring in consumer behavior, consumer engagement approaches, digital marketing approaches using websites, mobile applications, social media communities and service marketing strategies. Students, through this case, can relate the importance of virtual space in engaging consumers and the importance of the latter in addressing the dynamicity of consumer behavior, especially affected by sudden environmental change, such as the COVID-19 pandemic. The case study also subtly highlights the importance of collaboration with suppliers in an aggregator business model to capture the essence of changing consumer behavior. This case study is appropriate for students having previous knowledge of Rusbolt’s investment model and skinner’s operant behavioral model of consumer behavior and their application in service marketing. Besides, students must be aware of the online business model and aggregator businesses in the service industry of the UAE. The case study purports to motivate critical analytical thinking among students and build their understanding of the importance of consumer behavior for business sustenance. Supplementary materials Teaching notes are available for educators only. Subject code CCS 8: Marketing.

Multiple Myeloma: Risk Adapted Use of Plerixafor for Stem Cell Mobilization Prior to Autologous Stem Cell Transplantation is Effective and Cost Efficient

BackgroundWe used plerixafor in ‘a risk adapted approach’ for stem cell mobilization for multiple myeloma (MM) patients prior to autologous stem cell transplantation (ASCT). Patients and MethodsBetween January, 2017 and December, 2019 105 consecutive patients of MM were recruited (Study Cohort). Patients received inj G-CSF 10 µg/kg in 2 divided doses for 5 days. Day 4 peripheral blood (PB) CD34+ count was used as a guide; if count was < 20 cells/µl, patients received plerixafor. For those with ≥ 20 cells/µl apheresis was commenced on day 5. We compared their outcome with 156 MM patients transplanted between 2012 and 2016 with G-CSF mobilized PB stem cells (Control Cohort). Primary end point was to collect ≥2.0 × 106 CD34+ cells/kg (minimal harvest). Secondary end points were: no of apheresis sessions, percentage of patients with optimal stem cell harvest (≥4.0 × 106 CD34+ cells/kg) and cost analysis. An intent to treat analysis was done. Result96.2% of patients achieved ≥ 2.0 × 106 CD34+ cells/kg in the study cohort vs. 87.2% in the control cohort, P < .01. Mean apheresis sessions were 1.5 vs. 1.7 respectively, P < .014 . Optimal stem cell harvest was 29.5% vs. 16%,P = .23. Days for neutrophil engraftment (P < 0.025) and for IV antibiotics (P < .0017) were favorable for the study cohort. Incremental cost effectiveness ratio was $ 15.80/- and $ 10.56/- per 1% increase to achieve a minimal and optimal harvest. ConclusionPlerixafor in this risk adapted strategy resulted in successful mobilization, decreased time to engraftment and was cost effective.

Exploring the Constituent Elements of a Successful Mobile Health Intervention for Prediabetic Patients in King Saud University Medical City Hospitals in Saudi Arabia: Cross-sectional Study.

BackgroundSelf-management of prediabetic patients is crucial since they are at high risk of developing type 2 diabetes. Mobile health (mHealth) apps could contribute to potentially reducing the burden of diabetes by supporting the self-management of prediabetic patients.ObjectiveThis study aimed to explore the constituent elements of a successful mHealth intervention for prediabetic patients in King Saud University Medical City (KSUMC) hospitals in Saudi Arabia using the Centre for eHealth Research (CeHRes) roadmap.MethodsThis study used the CeHRes roadmap as a developmental guideline for proposing mHealth app features for self-management of prediabetic patients and was performed in 3 phases with one round in each phase. First, a contextual inquiry was conducted via an online self-administered questionnaire for both health care providers and patients. Second, the value specification phase elaborated on the outcomes from the contextual inquiry phase. Finally, prototype user design was performed in cocreation with end users. The design phase was also conducted via an online self-administered questionnaire to evaluate the proposed features of mHealth apps by prediabetic patients.ResultsA total of 20 health care providers participated in the study. The results revealed that the most powerful intervention for prediabetes was a combination of medication, physical activity, and healthy diet plans (12/20, 60%). Furthermore, the most common challenge faced by prediabetes patients was patient adherence to healthy diet and physical activity recommendations (10/20, 50%). Almost all patients believed that mHealth apps would be useful for prediabetic patients. A total of 48 prediabetic patients participated in the study. The results indicated that the most powerful intervention for prediabetic patients is a combination of healthy diet and physical activity plans (21/48, 44%), and the most frequent challenge that may lead the patients to discontinue the current intervention was the commitment to a physical activity plan (35/48, 75%). Furthermore, 15% (17/48) of patients use well-being and health apps to manage their current health status. The most common difficulties faced by the patients were navigating app features (mean 2.02 [SD 1.7]) followed by the app language (mean 1.88 [SD 2.0]); these difficulties occurred at a significantly higher rate among those with secondary or lower educational levels as compared to undergraduate and postgraduate levels (P<.05). Finally, the features proposed in the prototype design scored more than 2.5 points higher and indicate the need for these features to be included in the mHealth app.ConclusionsThis study aimed to provide real-world insights into the development of an mHealth app for a diabetes prevention intervention by involving both health care providers and prediabetic patients in KSUMC hospitals. Therefore, the proposed app, which comprises all necessary features, may aid patients with prediabetes in self-management and making changes in their lifestyle.

The Role of Emotions in Mobilization of Society to Fight Climate Change: Constructing Emotional State to Inspire Mass Movement

How do emotions contribute to mobilizing the international community to join massive protests against climate change? Although it is common to superficially state that protests are full of various emotions, it remains unclear how emotions become collective on the international level and how they ensure the spread of mass mobilization. This research paper examines the process of collectivization of emotions and how it explains mass mobilization in the case of international climate change strikes. This paper raises the question of how the emotional environment was favourably constructed in Greta Thunberg’s case in order to mobilize international society to join climate change strikes, and it aims to reveal how group emotions play an important role in successful international mobilization. Based on Sarah Ahmed’s theory of cultural politics of emotions and James M. Jasper’s theory linking emotions and social movements, it is assumed that specific emotions were circulated to create a distinct emotional environment that inspired the international community to join Thunberg’s climate strike. An Emotional Discourse Analysis revealed that Thunberg’s speeches are full of emotional potential that provokes reactive emotions such as fear, anger and hope in the global society and establishes an injustice-based framing of the problem as well as the dichotomy between the political elite and the global society. This study contributes to the research field of emotions in international relations by exploring in more depth the collectivization of emotions and expands the theory of cultural politics of emotions to include explanations of international politics phenomena such as mass mobilization.

Feasibility and Kinetics of CD34+ Hematopoietic Cells Mobilization By Low-Dose Pegfilgrastim in Lymphoma Patients

▪Introduction: Hematopoietic stem cell rescue with autologous peripheral blood stem cells (PBSC) following high-dose chemotherapy has been used for the treatment of lymphoma and myeloma. Granulocyte colony-stimulating factor (G-CSF) is used for PBSC mobilization but data on PBSC mobilization by pegfilgrastim is limited. Recent studies showed successful PBSC harvest by single dose of pegfilgrastim given at 6mg or 12mg within 4 days after chemotherapy in patients with malignant lymphoma. However, administration of pegfilgrastim early after chemotherapy administration induces overshoot of neutrophils, which may result in rapid plasma clearance of G-CSF due to internalization of the G-CSF/G-CSF receptor complexes via endocytosis in neutrophils. Previous studies demonstrated that day 7 injection of pegfilgrastim in the course of chemotherapy mitigated the neutrophil overshoot compared to day 4 injection of pegfilgrastim. We hypothesized that day 7 administration of lower dose 3.6mg pegfilgrastim could avoid neutrophil overshoot and efficiently mobilize PBSCs. Here we show the kinetics of CD34+ PBSC mobilization after 3.6mg pegfilgrastim given on day 7 in the course of chemotherapy.Patients and Methods: Between February 2016 and May 2017, twenty patients with malignant lymphoma enrolled in this study (14 DLBCL, 2 AITL, 2 ALCL, 1 ATLL, 1 FL). Median age was 54 (range 30-65). Eight patients had clinical stage III-IV. Median number of prior chemotherapy was 0 (range 0-2). All patients received cytotoxic chemotherapy (13 CHOP, 2 DeVIC, 2 ESHAP, 1 DHAP, 1 EPOCH, 1 HD-AraC) on day 1 and 3.6mg of pegfilgrastim was administered subcutaneously on day 7. Peripheral blood CD34+ cell counts were analyzed from day 11 to 14 after chemotherapy by flowcytometric analysis using single platform method based on ISHAGE guideline. The primary objective is to clarify the kinetics of peripheral blood CD34+ cells without harvesting intervention. CD34+ values on each time point is statistically tested using one-sample t-test. To visualize the primary result, bar graph with mean and its confidence interval on each day is represented with the reference line (Figure). The secondary objectives are to search peak point of CD34+ cell counts after each chemotherapy regimen and the feasibility of pegfilgrastim administration on day 7. Successful mobilization was defined as to achieve more than 10×106/L peripheral blood CD34+ cells on any time points between day 11 and 14. All patients were assessed for toxicity according to the National Cancer Institute Common Toxicity Criteria, version 4.0. This study was approved by the institutional review board and conducted in accordance with the Declaration of Helsinki.Results: Successful mobilization was achieved in 19 of the 20 patients (95%). Mean number (SD) of WBC (×109/L) on each day between day 11 and day 14 was 5.4 (3.7), 11.4 (9.1), 14.2 (9.1) and 13.9 (7.4), respectively. Mean number (SD) of CD34+ cells (×106/L) on each day between day 11 and day 14 was 20.3 (22.5), 38.0 (35.7), 40.3 (39.8), and 40.1 (53.5), respectively. The 98.75% confidence interval [CI] of CD34+ cells (×106/L) on each day between day 11 and day 14 was [6.39-34.22], [16.16-60.25], [15.77-64.97] and [7.09-73.16], respectively (Figure). The number of CD34+ cells on day 12 or 13 showed significantly higher than 10×106/L CD34+ cell (P = 0.0022 and 0.0030, respectively) (Figure). We then compared the peak of CD34+ cells in a peripheral blood in each chemotherapy regimens. The peak day of CD34+ cell in patients who received CHOP regimen was day 13 (mean 54.3 ×106/L, range 15.8-151.0×106/L) . However, in 4 of 5 patients who received platinum containing regimen, CD34+ cells failed to reach the peak before day 14 because of prolonged myelosuppression. The number of prior chemotherapy regimen (0 vs 1-2) was not associated with the kinetics of CD34+ cells (p = 0.35). No infectious events including febrile neutropenia were observed. Pain and LDH elevation (Grade 1-2) were the main adverse events related to pegfilgrastim administration. We had not detected any severe adverse events.Conclusion: Our data indicated that 3.6mg pegfilgrastim on day 7 can efficiently mobilize CD34+ cells to peripheral blood without any severe adverse events. [Display omitted] DisclosuresTeshima:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Kyowa-Hakko Kirin: Research Funding; Pfeizer: Research Funding; Chugai: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Brentuximab Vedotin Plus Bendamustine Is an Effective Salvage Regimen for Pediatric Patients with Relapsed Hodgkin Lymphoma

Background :Pediatric patients with relapsed/refractory Hodgkin Lymphoma have superior outcomes when achieving a complete remission prior to autologous stem cell transplant (ASCT). Optimal salvage regimens need to be identified as current approaches result in complete responses (CR) in approximately 25-35% of patients. The combination of brentuximab vedotin and bendamustine is highly active in adult patients with relapsed/refractory Hodgkin Lymphoma, but has not been evaluated in the pediatric population. We report our preliminary experience regarding the safety and efficacy of brentuximab vedotin and bendamustine prior to stem cell transplant (SCT) in pediatric patients treated for relapsed Hodgkin lymphoma at a single center.Methods:We performed a retrospective review of pediatric patients with relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine between April 2016 to July 2017. Patients received an infusion of 1.8mg/kg of brentuximab vedotin on Day 1 with bendamustine 90mg/m2 on Days 1 and 2 of 3-week cycles. Response assessment was performed and repeated following 2-3 cycles of therapy. Patients went on to SCT after achieving a CR or best response at the discretion of the treating physicians. Patients resumed post-transplant treatment with brentuximab vedotin as monotherapy for up to 16 doses.Results:Five patients (1 female, 4 males) with a median age of 16.5 years at the time of relapse (range, 12.2 -17.9 years) were treated with the combination of brentuximab/bendamustine. Four patients were in first relapse and 1 was treated in second relapse nine months following a prior ASCT. Patients received a median of 5 cycles of therapy (range 2-5 cycles), with 2 patients receiving an additional cycle of brentuximab monotherapy prior to proceeding to SCT. The main toxicity observed was infusion-related reactions, with 2 patients experiencing anaphylaxis. These individuals were able to continue planned therapy following desensitization against brentuximab. All patients were in complete remission by PET prior to SCT. Four patients underwent successful stem cell mobilization and collection. The individual treated following second relapse received an allogeneic transplant from a matched unrelated donor. All patients are alive with no evidence of disease a median of 11.3 months since beginning salvage therapy (range 1.2-15 months). Four patients are a median of 6.5 months (range 4-11 months) post-SCT and continue on brentuximab monotherapy, with 1 individual currently awaiting ASCT.Conclusions :Combination therapy with brentuximab vedotin and bendamustine was highly active in pediatric patients with relapsed Hodgkin lymphoma and would compare favorably with currently accepted salvage regimens. Incidence of infusion-related reactions can be minimized through the use of adequate premedication. These results support further evaluation of this regimen in the context of a multicenter prospective clinical trial. DisclosuresCurran:Novartis: Consultancy; Juno Therapeutics: Research Funding. Kernan:Gentium: Other: NAK received grants from Gentium during the conduct of the study, and her research was supported by The National Cancer Institute of the National Institutes of Health under award number P30 CA008748; the content is solely the responsibility of the author .

Novel Lineage Depletion and Manufacturing Allows for Unprecedented Preservation of Autologous Blood Stem Cells for Gene Therapy of Fanconi Anemia Complementation Group Α

A hallmark of the rare, monogenic disorder called Fanconi anemia (FA) is an accelerated decline in hematopoietic stem cells (HSC) leading to bone marrow (BM) failure. Long-term treatment requires hematopoietic cell transplantation (HCT) from an unaffected donor, but success of this approach in ~70% of the patients lacking a matched sibling is associated with potentially severe side effects. Gene therapy could be an alternative, correcting the genetic defect in the patient's own HSC and negating the need for a HCT donor. Building on previous FA gene therapy studies, we developed an optimized protocol for lentivirus (LV)-mediated FANCA gene transfer into HSCs from FA-A patients [Becker, P. Human Gene Therapy, 2010]. This phase I clinical trial incorporates vector recommendations from the International FA Gene Therapy Working Group. Three patients have been treated on this trial to date (National Clinical Trials Registry ID: NCT01331018). This protocol collects unmanipulated HSC from BM or mobilized leukapheresis (mAPH) and does not include conditioning prior to cell infusion. In the first two patients enrolled, harvested BM demonstrated reduced CD34+ cell numbers and CD34 expression (Figure 1). In the first patient, direct enrichment of dimly CD34+ cells was very inefficient. Thus, for the second patient the enrichment step was eliminated. While this processing change preserved more of the CD34+ cells and improved transduction and viability, it required a prohibitive amount of LV vector. To reduce vector needs and preserve available CD34+ cells for future FA patients, we developed a novel strategy to deplete lineage+ (CD3+, CD14+, CD16+ and CD19+) cells from both mAPH and BM products. This process efficiently depletes >90% of lineage+ cells from healthy donor cell products while retaining ≥60% of the initial CD34+ cell fraction, reduced total nucleated cells (TNC) by 1-2 logs and maintained improved transduction and viability following gene transfer. Most importantly, transduced lineage- cell products engrafted in an immune deficient mouse model equivalent to that of purified CD34+ cells from the same donor when transplanted at matched CD34+ cell doses. This novel selection strategy has been approved by the regulatory agencies and a third patient was treated in July 2017 with this approach. Patient 3 is a 5-year old male with confirmed FA-A by complementation studies. Baseline ANC averaged 1.6 K/mcL and baseline platelet counts averaged 31 K/mcL in the 6 months prior to treatment, with declining ANC and platelets over a 4 year interval prior to gene therapy. Successful mobilization of CD34+ cells was achieved with combination filgrastim (16µg/kg BID or 32µg/kg/day) and plerixafor (240µg/kg). Two, successive apheresis collections resulted in 8.5×1010 TNC containing 1.6×108 CD34+ cells. A total of 5×1010 TNC were subjected to lineage depletion, resulting in a 94% reduction in TNC and a 55% retention of available CD34+ cells. A total of 52.4×106 CD34+ cells were transduced at 5 IU/cell, resulting in a final cell dose of 2.4×106 CD34+ cells per kg. We observed a VCN of 1.8 copies per cell and viability of the final cellular product was 99.3%. Infusion was well-tolerated and a fourth patient is expected to be treated in the Fall of 2017. This novel method of depleting lineage positive cells reduced TNC counts to feasible numbers for transduction while maintaining high numbers of CD34+ cells, a strategy which could have benefits in other disease targets for gene therapy. [Display omitted] DisclosuresAdair:Rocket Pharmaceuticals: Consultancy, Equity Ownership, Patents & Royalties, Research Funding; CalImmune Inc.: Consultancy. Becker:GlycoMimetics, Inc.: Research Funding. Kiem:Rocket Pharmaceuticals: Consultancy, Equity Ownership, Patents & Royalties, Research Funding.

VRD-CEP: An Effective and Tolerable Chemo-Mobilization and Debulking Regimen for Multiple Myeloma

Introduction: Autologous stem cell transplant is the standard of care for fit patients with multiple myeloma (MM). However, many patients experience inadequate stem cell harvest after myeloid growth factor-based mobilization or suboptimal response to induction therapy. In the setting of high disease burden or heavy pretreatment, combination chemotherapy regimens, sometimes with addition of novel agents, may offer successful mobilization and debulking and include VTD-PACE, DCEP, and V-DCEP. We sought to offer a mobilization regimen that could 1) overcome mobilization failure and 2) debulk aggressive or refractory disease. We formulated the novel regimen VRD-CEP to achieve tolerability similar to that of DCEP but improve efficacy by combining a second-generation IMiD with a PI.Methods: We performed a retrospective, single-institution evaluation of fit MM patients with history of inadequate mobilization, inadequate response to induction, or aggressive disease characteristics. Patients received bortezomib 1 mg/m2 SC days 1, 4, 8, and 11; DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) in standard fashion days 4-7; and lenalidomide 25 mg daily days 4-7 and again upon achieving platelet > 50. Patients received filgrastim 10 mcg/kg SC beginning day 10.Results: Five patients were available for analysis; the median age was 59 (range 32-71). 2 patients were over 65, and 1 had ESRD. 2 patients underwent prior unsuccessful G-CSF + plerixafor mobilization, 2 patients had suboptimal response to induction, and 1 patient had aggressive disease features (plasmablastic histology, del 17p) with complete marrow replacement; 4 of 5 had ISS stage III disease. All patients received 1 cycle of the regimen. Three of the 4 mobilization patients achieved deepening of response based on M-protein or serum free light chains; one patient achieved near-complete elimination of plasma cells in the marrow and free light chain ratio normalization but could not undergo harvest due to logistical reasons. 3 of 5 patients were considered to have a PR or better. All patients treated with mobilization intent collected > 6 million CD34+ cells/kg (median 7.86; range 6.07-10.58 million/kg). The median time from the start of DCEP to apheresis was 13.5 days (range 13-18); the median number of apheresis days was 1.5 (range 1-3). No patients required dosing of plerixafor.Toxicities were acceptable. Grade 4 thrombocytopenia occurred in 3 patients, grade 4 neutropenia occurred in 4, and PRBC transfusions were given to 2. 1 patient was hospitalized for neutropenic fever. 1 patient developed reversible grade 2 renal insufficiency, and 1 patient developed grade 3 hyponatremia attributed to cyclophosphamide. No patients experienced worsening neuropathy, syncope, hypotension, deep vein thrombosis, grade 3-4 nausea/vomiting, or diarrhea. Patient-specific details are listed in Table 1.Discussion: Stem cell mobilization using G-CSF and plerixafor may be subject to inadequate yields in 1-40% of patients. Patients with significant residual plasma cell marrow involvement may require additional therapy to achieve adequate mobilization and cytoreduction prior to autologous transplant. VTD-PACE, DCEP, and V-DCEP have shown efficacy in relapsed or refractory MM patients. Such regimens are also useful for chemo-mobilization of stem cells. However, the efficacy of DCEP in the relapsed/refractory setting may be limited (40-50%), and VTD-PACE may have more limited applicability due to its higher toxicity burden. We believe that the addition of bortezomib and lenalidomide to DCEP achieves the desired potency to debulk refractory or high-risk disease while maximizing tolerability. More significantly, mobilization results were excellent, and we were able to achieve excellent stem cell yields in patients who had experienced inadequate growth factor mobilizations. The regimen merits further exploration in a larger cohort of patients.Conclusion: In a preliminary cohort of 5 MM patients, VRD-CEP appears to be an effective and safe mobilization regimen in patients with residual marrow disease or those who failed prior mobilization attempts. VRD-CEP led to efficient cytoreduction in patients with high-risk cytogenetics and heavy burden of disease. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Phase 1/2 Study of Carfilzomib Combined with Rituximab, Ifosfamide, Carboplatin and Etoposide (C-RICE) in Patients with Transplant-Eligible, Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

Background: The CORAL study highlighted the need to develop novel salvage regimens in R/R DLBCL previously treated with R+CHOP. Overall response rate (ORR) to second line chemotherapy (either RICE or RDHAP) was 51% in patients previously treated with R-CHOP with a 3-year progression free survival (PFS) of only 30%. In the SCHOLAR-1 study, pts with chemo-refractory disease had a worse prognosis with ORR of approximately 26% and a median overall survival (OS) of 6-7 months. We previously demonstrated that 1) the ubiquitin-proteasome system (UPS) plays an important role in acquired rituximab-chemotherapy resistance in DLBCL and 2) that carfilzomib (CFZ), a selective, irreversible proteasome inhibitor, overcomes rituximab-chemotherapy in lymphoma pre-clinical models. We hypothesize that targeting the UPS with CFZ could result in higher response rates and improved outcomes following high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) in R/R DLBCL pts.Methods: We are conducting a single-center, open-label, prospective Phase I/II clinical trial evaluating the safety, efficacy, and pharmacokinetics/pharmacodynamics (PK/PD) of CFZ in combination with R-ICE in HDC-ASCT eligible R/R DLBCL (NCT01959698). Here, we present the results of the Phase I part of the study. Classic 3+3 dose escalation of CFZ was utilized for the phase 1 portion. Primary objectives were to determine the maximum tolerated dose (MTD) and examine the dose-limiting toxicities (DLT) of CFZ in combination with R-ICE. Secondary objectives include feasibility of successful mobilization of autologous stem cells, preliminary evaluation of activity and PK/PD analysis. Patients received CFZ on days 1, 2, 8, 9, rituximab on day 3 followed by ICE (days 4-6) at standard doses. Cycles were repeated every 21 days for a maximum of 3 cycles before HDC-ASCT. Toxicity was assessed using NCI CTCAE version 4; responses were assessed after 2 and 3 cycles using revised Cheson criteria.Results: As of July 20th, 2017, a total of 14 pts have been enrolled in the phase 1 portion at 10 mg/m2 (n=3) (dose level 1 [DL1]), 15 mg/m2 (n=3) (DL2), 20 mg/m2 (n=3)(DL3), 20 mg/m2 d1-2, 27 mg/m2 d8-9 (n=3)(DL4), and 20 mg/m2 d1-2, 36 mg/m2 d8-9 (n=2)(DL5). Median age 60 yrs, 64% males, median time from diagnosis 14.8 (4.1-77.3) mo, 6/14 (43%) were primary refractory, 5/14 pts have a germinal center B-cell like (GCB) subtype, 8/14 pts have a non-germinal center (non-GBC subtype) by Han's criteria, 1 pt has T cell/histiocyte rich large cell lymphoma. Two pts have double hit (DL) DLBCL by FISH studies and 2 have a sole MYC rearrangement. With one more dose-level to test (DL6), no DLTs have been recorded so far. The MTD is yet to be defined. Majority of the grade 3/4 drug-related adverse events (AEs) reported were hematological (thrombocytopenia- 71%, anemia- 50%, neutropenia- 43%, lymphopenia 7%, febrile neutropenia 14.3%). Grade 3 non-hematological AEs include gastrointestinal hemorrhage (1), device-related infection (1), abscess at biopsy site (1), dehydration (1), hyperglycemia (1), hypokalemia (1), hypophosphatemia (1), headache (1), dyspnea (1), pulmonary embolism (1). Grade 4 non-hematological AEs were hypocalcemia (1) and hypokalemia (1). Preliminary results demonstrate an ORR of 64% (50% CR, 14% PR) (Figure 1). Interestingly, an ORR of 100% was observed in pts with relapsed non-GCB DLBCL subtype (all CRs). In contrast, all patients with primary refractory DLBCL fared poorly (1- partial response, 3-stable disease, 2- progressive disease) and were unable to proceed to HDC-ASCT. All responding patients (N=8) underwent successful stem cell collection and received HDC-ASCT. The median TTP post HDC-ASCT, PFS and OS have not been reached. PK/PD/correlative data will be presented at the meeting.Conclusion: C-RICE is well tolerated in pts with R/R DLBCL with toxicities comparable to RICE chemo-immunotherapy. The selective higher CR rate (100%) observed in non-GCB DLBCL highlights the effects of CFZ in NFκB activity and its contribution to chemotherapy resistance. Our data suggest that non-GCB DLBCL benefit significantly from incorporating CFZ into second line therapy and HDC-ASCT. The phase II of the study will commence shortly and tailoring enrollment to non-GCB R/R DLBCL may optimize treatment options to all subtypes of R/R DLBCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Success factors driving consumer reuse intention of mobile shopping application channel

PurposeDue to fierce competition in the mobile retailing market, it is desirable to identify the success factors driving consumers to reuse a mobile shopping application. This research intends to develop a model for mobile shopping app success by integrating an e-commerce systems success (ESS) model and sales promotion benefits and parasocial interaction literatures.Design/methodology/approach302 useable online questionnaires were obtained. The data analysis was conducted using the structural equation modelling.FindingsThe results indicate the validity of the ESS model in predicting consumers' reuse intention of mobile shopping apps where three quality dimensions of system, information and service facilitate both perceived value and user satisfaction, which in turn generates reuse intention. Furthermore, savings and entertainment denoting the utilitarian and hedonic sales promotion benefits have positive impact on perceived value but have no influence on satisfaction. Parasocial intention between consumers and sellers facilitates both value perception and satisfaction.Originality/valueThis research contributes to the mobile retailing literature by identifying the success factors driving consumers' continuance intention of mobile shopping apps. Theoretically, it validates and extends the ESS model in mobile shopping app context by identifying savings, entertainment and parasocial interaction as additional success factors. Based on the findings, two approaches are proposed to suggest mobile retailers design a successful mobile shopping app.

MCP (Mitoxantrone/Chlorambucil/Prednisolone) Chemotherapy Impairs the Subsequent Collection of Stem Cells in Comparison to CHOP Induction in Patients with Indolent Lymphomas - Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG).

Background: Myeloablative radio-chemotherapy followed by autologous stem cell transplantation (ASCT) significantly prolongs remission duration as compared to interferon alpha maintenance after conventional chemotherapy induction and is a well established treatment option in younger high risk patients with indolent lymphoma. This randomized trial compared the rate of successful stem cell mobilization after initial therapy with either MCP or CHOP in younger patients (< 60 years).Methods: Previously untreated patients with advanced stage indolent lymphoma were randomly assigned to 6 cycles of CHOP or MCP for remission induction. Patients <60 years of age who were subsequently assigned to ASCT received one additional cycle of Dexa-BEAM (dexamethasone, BCNU, etoposide, cytarabine, melphalan) for stem cell mobilization. A minimum of 2x 2.0x106/kg bw CD34+ cells (including back-up) was estimated as appropriate for ASCT. Stem cells were collected and cryopreserved without any purging procedure.Results: According to initial randomization, 45 of 79 patients assigned to ASCT had been treated with CHOP and 34 patients with MCP. 58 (73%) had follicular lymphoma, 13 (16%) mantle cell lymphoma and 8 (10%) lymphoplasmacytic lymphoma. Dexa-BEAM was well tolerated in all patients with a moderate rate of severe infections (13%) or other complications. After CHOP induction, stem cell collection was successfully performed in 42 of 45% cases (93%, 95% CI 82% to 99%). In contrast, stem cell collection was successful in only 15 of 34 patients after MCP chemotherapy (44%, 95% CI: 27% to 62%) (p=0.0003).Conclusions: Initial therapy with MCP significantly impairs the ability to collect stem cells and should be avoided in first line therapy of patients who may qualify for myeloablative consolidation followed by ASCT

Gemcitabine, dexamethasone and cisplatin (GDP) is an effective and well-tolerated mobilization regimen for relapsed and refractory lymphoma: a single center experience

Background/aim Gemcitabine, dexamethasone and cisplatin (GDP) is a well-established salvage regimen for relapsed and refractory lymphomas. In this study, we aimed to share our experience with the patients who received GDP/R-GDP (rituximab-gemcitabine, dexamethasone and cisplatin) for stem cell mobilization. Materials and methods Data of 69 relapsed and refractory Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL) patients who received GDP/R-GDP as salvage chemotherapy in our center between July 2014 and January 2020 were retrospectively evaluated. After the evaluation of response, 52 patients had a chemosensitive disease and underwent mobilization with GDP/R-GDP plus G–CSF (granulocyte colony-stimulating factor). Collected CD34+ stem cells and related parameters were compared in terms of diagnosis of HL and NHL, early and late stage, patients who did not receive RT and those who received RT, and patients aged under 60 and over 60. Results On the 15th day on average (range 11–20), a median number of 8.7 × 106 /kg (4.1–41.5) CD34+ stem cells were collected in 51 (98%) of our 52 chemosensitive patients and 1 (2%) patients failed to mobilize. We observed acceptable hematological and nonhematological toxicity. The targeted amount of 2 × 106 /kg CD34+ stem cells was attained by 98% (n: 51) patients, and all of them underwent autologous stem cell transplantation. Moreover, low toxicity profiles provide outpatient utilization option clinics with close follow-up and adequate supportive care. Conclusion We suggest that GDP/R-GDP plus G-CSF can be used as an effective chemotherapy regimen for mobilizing CD34+ stem cells from peripheral blood in relapsed and refractory lymphoma patients due to low toxicity, effective tumor reduction, and successful stem cell mobilization. It can also be assumed that the GDP mobilization regimen may be more effective, especially in patients with early-stage disease and in HL patients.

Stem Cell Mobilization in Multiple Myeloma: Comparing Safety and Efficacy of Cyclophosphamide +/- Plerixafor versus Granulocyte Colony-Stimulating Factor +/- Plerixafor in the Lenalidomide Era

Growth factor and chemotherapy-based stem cell mobilization strategies are commonly used to treat patients with multiple myeloma. We retrospectively compared 398 patients mobilized between 2017 and 2020 using either cyclophosphamide (4 g/m2) plus granulocyte colony-stimulating factor (G-CSF) or G-CSF alone, with on demand plerixafor (PXF) in both groups. Although total CD34+yield was higher after chemomobilization compared with G-CSF +/- PXF (median, 13.6×106/kg versus 4.4×106/kg; P < .01), achievement of≥2×106CD34+ cells (95% versus 93.7%; P=.61) and rates of mobilization failure (5% versus 6.3%; P=.61) were similar. Fewer patients required PXF with chemomobilization (12.3% versus 49.5%;P < .01), and apheresis sessions were fewer (median, 1 [range, 1 to 4] versus 2 [range, 1 to 5]). The rate of complications, including neutropenic fever, emergency department visits, and hospitalizations, was higher after chemomobilization (30% versus 7.4%;P < .01). Previous use of ≤6 cycles of lenalidomide did not impair cell yield in either group.The median cost of mobilization was 17.4% lower in the G-CSF +/- PXF group (P=.01).Between group differences in time to engraftment were not clinically significant. Given similar rates of successful mobilization, similar engraftment time, and less toxicity and lower costs compared with chemomobilization, G-CSF with on-demand PXF may be preferable in myeloma patients with adequate disease control and limited lenalidomide exposure.