Successful Mobilization Research Articles

SwedeAmp—the Swedish Amputation and Prosthetics Registry: 8-year data on 5762 patients with lower limb amputation show sex differences in amputation level and in patient-reported outcome

Background and purpose — For want of national guidelines for lower limb amputation (LLA) the quality registry SwedeAmp was started in 2011 to increase knowledge around LLA and prosthetic rehabilitation. We now present data from the first 8 years of registration.Patients and methods — We present descriptive data from the first 8 years (2011–2018) of registration. Patient-reported outcome was collected at baseline and at follow-up 12 and 24 months after surgery for patients with prosthetic supply and included generic (EQ-5D-5L) and amputee-specific (e.g., LCI-5L and Prosthetic Use Score) measures. Sex differences were investigated.Results — As at December 31, 2018, 5,762 patients, 7,776 amputations, 2,658 prosthetic supplies, 1,848 baselines, and 2,006 follow-ups were registered. 61% of the patients were male, and mean age by the time of the first registered amputation was 74 years (SD 14). Women were older, more frequently had vascular disease without diabetes and more often underwent amputation at a higher level compared with men (p < 0.001). Time from amputation to fitting of first individual prosthesis was median 69 days (6–500) after transtibial amputation (TTA) and 97 days (19–484) after transfemoral amputation (TFA). The outcomes were lower after TFA than after TTA.Interpretation — SwedeAmp shows sex differences concerning amputation level, diagnosis, and age, leading to the conclusion that women have worse preconditions for successful prosthetic mobility after LLA. With increasing coverage, SwedeAmp can provide deeper knowledge with regard to patients undergoing LLA in Sweden.

PERANCANGAN MOBILE AR DAN 3D VR WALKTHROUGH SEBAGAI MEDIA INFORMASI KAMPUS STEKOM SEMARANG BERBASIS ANDROID

Abstract The development of technology has entered the digital era of mobile, which required information media is more than just print brochures and official website, because it offered a solution for the design of a medium that can be run through mobile devices based on Android that are engaging, interactive, and follow the latest technology that augmented reality and virtual reality. The method used in this design is the System Development Life Cycle or SDLC, while supporting software used is Unity3D and Vuforia. Results from this study is the successful mobile AR and 3D-VR Walkthrough to implement and complete the on-campus media STEKOM information which has been used.

Usability Evaluation Model for Mobile Visually Impaired Applications

The usability of the mobile applications is the most important factor in developing, so the key to develop successful mobile applications is usability, especially for users have specific needs such as visually impaired. However, developers do not focus on visually impaired users. Moreover, there are limited studies and usability evaluation models for mobile applications for visually impaired so developers use just a modified usability evaluation methods which are not enough and useful to evaluate mobile applications for visually impaired, or they use general usability evaluation models. Therefore, using these methods or models is difficult for evaluator and not useful for visually impaired users. This study conducts Systematic Literature Review (SLR) to identify usability dimensions that help mobile applications developers and evaluators to evaluate mobile application for users which have moderate and severe visual impairment. The result shows that, six dimensions that have a significant impact on moderate and severe visually impaired users' satisfaction, who use mobile applications. These dimensions namely efficiency, effectiveness, satisfaction, errors, accessibility and understandability.

The Effects of Successful Aging in the Workplace on Technology Acceptance and Use Behaviour

ABSTRACT This study investigated the association between successful aging and mobile internet acceptance and use behavior in the workplace. A total of 221 participants responded to the survey. The constructs in the model were measured using successful aging in the workplace scale (SAW), the unified theory of acceptance and use of technology (UTAUT2). A mixed-method evaluation design was adopted in the study, which included quantitative and qualitative analysis methods. SAW was positively associated with UTAUT2 (β = ,856; p ⩽ 0,05), unassociated with BI (β = ,089;p = ,466) and USE (β = ,364; p = ,235). UTAUT2 was positively associated with BI (β = 1,110; p ⩽ 0,001) and USE (β = ,511; p⩽0,001); HT (β = ,713; p ⩽ 0,001) and FC (β = ,708; p⩽0,01) were positively associated with BI. BI was positively associated with USE (β =,391; p ⩽ 0,05). SAW was unassociated with BI (β = ,089; p = ,466; t = ,729), and USE (β = ,364; p = ,235; t = 1,189). The main result of this study was the positive association between SAW and UTAUT2, in contrast to the unassociation between the SAW and BI. The qualitative results showed the main differences between the SAW and the perception of the successful aging of employees.

Political Aspects of COVID-19 Epidemic Crisis in China

The global spread of coronavirus infection has given States the task of taking decisive measures to respond quickly and on a large scale to the challenge of existing management systems. China has demonstrated successful mobilization mechanisms to combat the negative effects of the pandemic: the necessary measures have been taken to inform the population and stop panic, control and prevent coronavirus, and mitigate the impact on the economy. However, the weak side was the inability to take priority measures in the face of uncertainty, which did not prevent the development of the epidemic at its initial stage. This provoked a search for those responsible among the Chinese leadership, becoming another source of tension in relations between China and the West. Despite the relative success of the measures taken, the situation in China itself remains tense: it faces challenges to prevent a re-outbreak of infection and to restore the economy in the face of information and economic pressure from the United States. In this context, the authors analyze the features of information support for measures taken in China to combat the spread of coronavirus infection and their impact on the domestic and foreign policy situation.

European Morality Politics in the European Union: The Case of Prostitution

Prostitution is a standard case of morality politics (MP), defined as a particular type of politics that engages issues closely related to religious and/or moral values, giving way to strong and uncompromising value conflicts in both societal and political spheres. This kind of issues have increasingly become a European policy matter due to their transnational nature and the tensions they create between different legal principles. Our hypothesis is that this leads to the emergence of a specific type of European morality politics (EMP) reflecting the particular constraints of the policymaking of the European Union (EU). The purpose of this article is to understand to which extent the rise of prostitution on the EU agenda alters usual patterns of MP to shape a distinctive type of EMP. Our findings suggest that prostitution characterizes EMP albeit with a significant difference, namely the challenge to regulatory inertia through the successful mobilisation of European values by some policy entrepreneurs to promote a neo-abolitionist approach.

Thin-layer chromatography with eutectic mobile phases—preliminary results

The presented paper is the first to show thin layer chromatography (TLC) analysis based on eutectic mobile phases (Deep Eutectic Solvents – DES). During the experiment 25 eutectic mixtures were investigated for their chromatographic properties. Most of them belong to the natural deep eutectic solvents (NADES) group. Also, new eutectic liquids based on phenolics and terpenes, not previously employed in analytical practice, were tested. The eutectic liquids were investigated as pure or diluted with solvents used in chromatographic routine: methanol, water, acetone, chloroform or diethyl ether. The analyses were carried out using classic and high performance silica gel plates. The working solution was a mixture of five alkaloids found in genus Chelidonium, namely sanguinarine, coptisine, chelerythrine, chelidonine, and berberine, with UV light detection of 366 nm. This report proves that eutectic TLC is possible and that the eutectic interactions play a crucial role in the separation process. In most of the tested modifications at least partial separation was achieved. The most successful mobile phase, which enabled separation of all the tested alkaloids, was the equimolar mixture of menthol and phenol with a 35% addition of methanol. The system was also effective in separating alkaloids in the real Chelidonium maius extract sample.

The Strategic Role Of the Local Communities in The Development Of Cross-Border Cooperation Between Ukraine And The EU (on the example of the Transcarpathian Region)

This article is devoted to the study of the implementation of cross-border cooperation between Ukraine and EU countries. Transcarpathia was chosen as the region for the study because it is here that Ukraine is bordering with four European states. The most important role in the implementation of cross-border programs belongs to the communities in the field provided by the local self-government bodies. It is they who have the relevant knowledge and experience to successfully implement projects and programs from different funding sources targeted for the development of cross-border regions. The successful development and success of Ukraine’s border territories largely depend on the successful mobilization and strategic use of funds.

Risk Factors for PoorAutologous Peripheral blood Stem Cell Mobilization among Lymphoproliferative Disease Patients

Objective: Autologous peripheral blood haemopoietic stem cell (PBSC) transplantation is a standard therapeutic option for eligible patients with lymphoproliferative disease (LPD). The prerequisite for autologous PBSC transplantation is the successful stem cell mobilization. This study is aimed to determine the factors associated with poor PBSC mobilization in LPD patient at our center.&#x0D; Materials and methods: This retrospective record review involved 39 multiple myeloma (MM) and 92 of lymphoma patients who had undergone PBSC mobilization from January 2009 until December 2016. Patients were mobilized with combination chemotherapy and granulocyte colony stimulating factor. Factors affecting mobilization including patient’s, disease and treatment characteristics werestudied.&#x0D; Results: Majority of patients were Malay (93.9%) with the mean age at mobilization of 41.4 years. The mean of CD34+ cell dosage was 9.6x106 cells/kg. Successful and poor mobilization was found to be 90.8% and 9.2% respectively. Multivariate analysis showed that the significant risk factors for poor mobilization were age of ≥ 60 years (adjusted OR=38.43, p=0.005) and PB CD34+ cell count, &lt;20 cells/uL (adjusted OR=132.69, p&lt;0.001).&#x0D; Conclusion:PB CD34+ cell count and age ≥ 60years were the main risk factors for poor PBSC mobilization. Thus, alternative strategies of mobilization is needed to reduce risk of poor mobilization in a such group of patient.&#x0D; Bangladesh Journal of Medical Science Vol.19(3) 2020 p.458-466

Plerixafor combined with standard regimens for hematopoietic stem cell mobilization in pediatric patients with solid tumors eligible for autologous transplants: two-arm phase I/II study (MOZAIC)

This study (NCT01288573) investigated plerixafor’s safety and efficacy in children with cancer. Stage 1 investigated the dosage, pharmacokinetics (PK), pharmacodynamics (PD), and safety of plerixafor + standard mobilization (G-CSF ± chemotherapy). The stage 2 primary endpoint was successful mobilization (doubling of peripheral blood CD34+ cell count in the 24 h prior to first apheresis) in patients treated with plerixafor + standard mobilization vs. standard mobilization alone. In stage 1, three patients per age group (2–<6, 6–<12, and 12–<18 years) were treated at each dose level (160, 240, and 320 µg/kg). Based on PK and PD data, the dose proposed for stage 2 was 240 µg/kg (patients 1–<18 years), in which 45 patients were enrolled (30 plerixafor arm, 15 standard arm). Patient demographics and characteristics were well balanced across treatment arms. More patients in the plerixafor arm (24/30, 80%) met the primary endpoint of successful mobilization than in the standard arm (4/14, 28.6%, p = 0.0019). Adverse events reported as related to study treatment were mild, and no new safety concerns were identified. Plerixafor + standard G-CSF ± chemotherapy mobilization was generally well tolerated and efficacious when used to mobilize CD34+ cells in pediatric cancer patients.

Trends in Abstinence and Retention Associated with a Medication-Assisted Treatment Program for People with Opioid Use Disorders.

Medication-assisted treatment (MAT) is an evidence-based program for patients with opioid use disorders. Yet, within the state of Utah, MAT had not been widely available, promoted, or adopted within the public sector. Recognizing the potential benefit, a collective impact approach was used to promote social change and increase the use of MAT in the community for treatment of opioid use disorders. Conduct a retrospective, observational case series study to measure the effect of a community-based, collective impact approach implementing the MAT program to improve the rate of abstinence and retention among individuals identified with an opioid use disorder in three Utah counties. The study was designed and implemented by the Utah Opioid Community Collaborative (OCC) using a collective impact approach, which included broad sector coordination (public-private collaboration), a common agenda, participation in mutually reinforcing activities, continuous communication, consistent measurement of results, and identification of a backbone organization. The MAT intervention program includes use of medications approved by the U.S. Food and Drug Administration in combination with counseling and behavioral therapies delivered within two community sites. Analysis was performed over time to describe the rate of abstinence and retention associated with participation in the MAT program during 2015 through 2017. Of the 339 identified with risk of an opioid use disorders, 228 enrolled in the MAT Program. At MAT enrollment, average age was 32.6 ± 8.2 years old and 58.0% were female. At 365 days after MAT enrollment, 84% of participants were abstinent from opioid substances and 62% from all illicit substances. Use of a collective impact approach provides a successful mobilization framework in Utah for increasing community engagement and expanding patient access to underresourced MAT programs while suggesting a high rate of abstinence from illicit substances at 12 months.

Technical requirements for organising successful mobility campaigns in citizen observatories

Traditional travel surveys are usually organised in a top-down manner, when data collection is commissioned by transport authorities. Recently, however, there has been an increasing tendency towards bottom-up initiatives when citizens and stakeholders initiate and implement data collection campaigns in citizen observatories. Citizen observatories are usually based on participatory sensing, i.e. data collection by volunteers using smart mobile devices. The ubiquity of smartphones and hardware developments make it a potentially useful instrument to have travel behaviour registered. However, creating a new citizen observatory remains technically difficult and labour-intensive. Today, citizen observatories have to be developed from scratch, which acts as a significant barrier to their implementation. Recently, an open, reusable and reconfigurable citizen observatory platform has been proposed. Through such a platform, ICT-agnostic stakeholders are able to initiate new citizen observatories in various domains.In this paper we have developed a general technical framework for a platform that can allow stakeholders to create citizen observatories, with the aim of collecting data on travel behaviour. The framework is based on the available functionalities of travel survey applications, elaborating on the potential limitations and enhancements of a citizen observatory platform compared to travel survey apps. First, we compared the functionalities of smartphone-based travel surveys and citizen observatories, which exposed the main areas of concern of citizen observatories compared to traditional travel surveys. Next, we developed a framework for the technical requirements to organise a citizen observatory for mobility. The three main stages in this framework are the collection of raw data, processing it into valuable behavioural and environmental information (e.g. travel modes, air pollution) and the feedback of this data to all stakeholders. Data validation should be applied in each stage and it is important to ensure user acceptance during the entire lifespan of the campaign. We highlighted points for attention that should be considered when developing a citizen observatory for mobility. Defining the required accuracy, representativeness and reliability in a specific campaign are key questions in the context of an acceptable rate of battery drain. The technical requirements developed in this paper reflect a ‘best-case scenario’ that will later be tested with specific use cases.

Trends in Abstinence and Retention Associated with a Medication-Assisted Treatment Program for People with Opioid Use Disorders

Background Medication-assisted treatment (MAT) is an evidence-based program for patients with opioid use disorders. Yet, within the state of Utah, MAT had not been widely available, promoted, or adopted within the public sector. Recognizing the potential benefit, a collective impact approach was used to promote social change and increase the use of MAT in the community for treatment of opioid use disorders. Objective Conduct a retrospective, observational case series study to measure the effect of a community-based, collective impact approach implementing the MAT program to improve the rate of abstinence and retention among individuals identified with an opioid use disorder in three Utah counties. Methods The study was designed and implemented by the Utah Opioid Community Collaborative (OCC) using a collective impact approach, which included broad sector coordination (public-private collaboration), a common agenda, participation in mutually reinforcing activities, continuous communication, consistent measurement of results, and identification of a backbone organization. The MAT intervention program includes use of medications approved by the U.S. Food and Drug Administration in combination with counseling and behavioral therapies delivered within two community sites. Analysis was performed over time to describe the rate of abstinence and retention associated with participation in the MAT program during 2015 through 2017. Results Of the 339 identified with risk of an opioid use disorders, 228 enrolled in the MAT Program. At MAT enrollment, average age was 32.6 ± 8.2 years old and 58.0% were female. At 365 days after MAT enrollment, 84% of participants were abstinent from opioid substances and 62% from all illicit substances. Conclusions Use of a collective impact approach provides a successful mobilization framework in Utah for increasing community engagement and expanding patient access to underresourced MAT programs while suggesting a high rate of abstinence from illicit substances at 12 months.

XIAOMI – TRANSFORMING THE COMPETITIVE SMARTPHONE MARKET TO BECOME A MAJOR PLAYER

Over the past six years, (between the period 2014 -2019), China's electronic information industry and mobile Internet industry has morphed rapidly in line with its economic performance. This is attributable to the strong cooperation between smart phones and the mobile Internet, capitalizing on the rapid development of mobile terminal functions. The mobile Internet is the underlying contributor to the competitive environment of the entire Chinese smartphone industry. Xiaomi began its operations with the launch of its Android-based firmware MIUI (pronounced “Me You I”) in August 2010; a modified and hardcoded user interface, incorporating features from Apple’s IOS and Samsung’s TouchWizUI. As of 2018, Xiaomi is the world’s fourth largest smartphone manufacturer, and it has expanded its products and services to include a wider range of consumer electronics and a smart home device ecosystem. It is a company focused on developing newgeneration smartphone software, and Xiaomi operated a successful mobile Internet business. Xiaomi has three core products: Mi Chat, MIUI and Xiaomi smartphones. This paper will use business management models from PEST, Porter’s five forces and SWOT to analyze the internal and external environment of Xiaomi. Finally, the paper evaluates whether Xiaomi has a strategic model of sustainable development, strategic flaws and recommend some suggestions to overcome them.

The impacts of agroforestry on agricultural productivity, ecosystem services, and human well-being in low-and middle-income countries: An evidence and gap map.

The impacts of agroforestry on agricultural productivity, ecosystem services, and human well-being in low-and middle-income countries: An evidence and gap map.

Comparing 4- and 6-week post-flap protocols in patients with spinal cord injury

Objective: For patients with spinal cord injury (SCI) who undergo flap surgery to treat pressure injuries (PIs), the optimal duration of post-operative bedrest to promote healing and successful remobilization to sitting is unknown. At the study center, the minimum duration of post-operative bedrest was changed from 4 to 6 weeks. The purpose of this study is to compare outcomes of patients who underwent flap surgery using bedrest protocols of different duration. Design: This was a retrospective review of all flap procedures completed at VA Puget Sound Health Care System from 1997 to 2016 to treat PIs in patients with SCI. Surgeries were excluded if they were not a flap (i.e. primary skin closure or graft), involved a non-pelvic region, or were a same-hospitalization revision of a prior surgery. The primary outcome of this investigation was the number of days between surgery and the first time the patient mobilized to sitting out of bed for 2 h with an intact surgical incision. Methods: 190 patients received a total of 286 flap surgeries from 1994 to 2016. A chart review of each case was completed to determine the planned duration of bedrest (4- vs 6-weeks), first date of successful mobilization out of bed for 2 h, length of stay post-surgery, and occurrence of complications such as dehiscence or need for operative revisions. Results: Among 286 primary surgeries, 171 surgeries used the 4-week protocol and 115 used the 6-week protocol. When compared to the 4-week protocol, patients treated with the 6-week protocol were slightly older, more likely to have a diagnosis of diabetes, and less likely to be current smokers. Healing was never achieved after 4 surgeries in the 4-week group and 2 surgeries in the 6-week group. With the analysis restricted to a single surgery per subject who achieved healing (109 treated with 4-week protocol and 75 with 6-week protocol), there was a significant difference in days until 2-h sitting: median 54 days for the 4-week protocol compared to 60 days for the 6-week protocol (p = 0.041). Up to about 60 days post-operatively, the 4-week protocol produced a greater proportion remobilized to sitting, and thereafter the proportion of patients successfully remobilized did not differ between protocols. Conclusions: The 6-week protocol was not associated with improved remobilization outcomes (reduced rates of dehiscence or surgical revisions), and the 4-week protocol resulted in a significantly shorter time to remobilization to sitting for 2 h as well as a shorter length of stay. We did not identify any subgroup of patients that benefited from the longer protocol.

Introduction to Special Issue: Critical Interventions on the Spaces and Practices of State Power

Many analyses of the 2011 uprisings and their aftermath 2011 uprisings have been built explicitly on social movements theory with a focus on specific episodes of social unrest. Others have employed procedural approaches from theories of democratization. The nation-level unit of analysis dominant in these approaches reproduces classic regime-character typologies and invokes questions about the relationship between regime type and successful social mobilization. This special issue explores the spaces and practices of state power beyond the conventional framework, giving special attention to space, time, and the multiple scales of relations of power. The contributors explore how these alternative approaches open up different questions into the operation of state power—some in the specific context of the uprisings and some in the course of more quotidian administration.

Analysis of factors associated with successful allogeneic peripheral blood stem cell collection in healthy donors

BackgroundThe collection of a sufficient number of stem cells is important for success of allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to investigate the factors associated with successful allogeneic peripheral stem cell (PBSC) collection in healthy donors. MethodsWe retrospectively reviewed clinical data of allogeneic PBSC collection in 175 donors from 2007 to 2017 at the National Cancer Center, Korea. This study analyzed factors associated with the CD34+ cell yield such as the characteristics of donors, including age, laboratory results before apheresis, and data of procedures on the first day. The CD34+ cell dose of ≥ 4.0 × 106/kg have recently been the accepted minimum recommended dose in allogeneic HSCT settings, and this was the target dose in our study. ResultsThe factors associated with the CD34+ cell yield were age (p = 0.007), baseline platelet (PLT) (p = 0.014), and pre-collection hematopoietic progenitor cells (HPCs) (p = 0.001) by multivariate analysis. This study represented that age, baseline platelet count, and pre-collection HPC count are important predictive factors as shown in other previous studies. ConclusionOur data suggest that young age, high baseline platelet counts and high HPC counts before collection might be useful for identifying successful mobilizers.

Administration of Plerixafor in Poor Mobilizers Allows Mobilization of Haematopoietic Progenitors: Clonogenic Potential and Engraftment Analysis

BACKGROUND Plerixafor (PLX) blocks the binding of stromal cell-derived factor to CXCR4, resulting in hematopoietic stem cell (HSC) release from the bone marrow. It has been successfully used as a mobilizing agent in poor mobilizers (PM). The best strategy is probably the "pre-emptive" (on demand) use, as it allows an "on time" identification of PMs, preventing collection failure and need for further mobilization. Usually a cut-off of &lt; 10/ μL CD34+ cell count at leukocyte recovery is used for PLXa dministration, while a minimum level is not defined, as mobilization may be obtained even with very low values. An important issue that has not been extensively explored so far is represented by the biological characteristics of the yields collected with PLX, especially clonogenicity, and its clinical counterpart, represented by the engraftment times observed after transplant. In this report we retrospectively analysed our data on the use of PLX in PMs, evaluated its efficacy and focused on the clonogenicity of collected stem cells and engraftment post auto transplant (ASCT). METHODS We collected data on PM patients mobilized with PLX between 2011 and 2019:Clinical data: mobilization and collection performance, transplant rate and engraftment times (days to PMN &gt; 500/uL).Biological data: Clonogenicity of HSC collected after PLX, measured by hematopoietic progenitor semi-solid cultures according to Stem Cell Technology. These clinical and biological data were then compared to those obtained in patients mobilized without PLX and in allogeneic donors who received G-CSF in the same period. RESULTS From January 2011 to June 2019 PLX was used in 73 mobilization cycles, performed in 64 patients. Patients characteristics are described in Table 1. 105 doses of PLX were given during 73 mobilization cycles (1,44 doses/cycle) and 93 collections performed (1,27/ cycle). Circulating CD34+ pre PLX administration were in median 6,81/µl (range: 0,27-21), while after treatment 26,20/µl (range: 4,8-155,4). Using a cut-off of ≥ 10/ μL CD34+, a successful mobilization was achieved in 67/73 cycles (success rate 91,7%). Overall 59 out of 64 patients achieved the collection target (92,2%) at any time and 54/64 have been transplanted (84,4%), the other 10 not yet due to mobilization failure (n=2), insufficient yield (n=3), clinical unfitness (n=2) or because too early (n=3). A median of 4 HPC bags were reinfused (range: 2-12) and median time to WBC engraftment was 10 days (8-21). Engrafment times are in line with those of MM and NHL patients mobilized without PLX in the same period of time (median: 10, range: 8-12) at our Institution. Interestingly, 33 out of 35 pts mobilized with PLX (94,2%), compared to 442/449 (98,4%) engrafted in ≤11 days. We analyzed the cellular composition of yields and clonogenicity of HSC collected in 3 different groups:Group A: PLX mobilization (n=93)Group B: chemo + G-CSF without PLX (n=755)Group C: G-CSF mobilization in allogeneic donors (n=206) We failed to demonstrate a statistical difference between clonogenicity in group A and B (p=0,691), while clonogenicity was slightly but significantly higher in group C compared to group A and B (p&lt; 0,001). Data are shown in tables 2,3 and 4. CONCLUSION In our cohort of patients, administration of PLX in PM resulted in successful mobilization of HPCs with good clonogenicity and engraftment potential. The use of PLX allowed an high proportion of patients to undergo ASCT. Disclosures No relevant conflicts of interest to declare.

Safety and Toxicity Profile of Pembrolizumab (PEM) in Combination with ICE Chemotherapy Followed By Autologous Stem Cell Transplantation for Relapsed/Refractory Classical Hodgkin Lymphoma: No Impairment in Stem Cell Mobilization or Engraftment

Background: Despite excellent outcomes in the front-line management of classical Hodgkin lymphoma (cHL), patients with relapsed or refractory disease typically undergo second-line cytotoxic chemotherapy before proceeding to consolidation with autologous hematopoietic stem cell transplant (autoHSCT). Pre-transplant F18-FDG-PET imaging is a well-established predictor of outcomes following autoHSCT; a complete metabolic response (CMR) to second-line therapy defined as a Deauville score 1-3 predicts a favorable outcome and is a requirement for transplant at many centers. The PD-1 pathway plays an important role in the pathogenesis of cHL and checkpoint inhibition with agents including PEM and nivolumab have shown efficacy as monotherapy in heavily pretreated disease. We hypothesized that the addition of PEM to ICE (ifosfamide, carboplatin, and etoposide) chemotherapy will increase the rate of CMR by PET-CT prior to autoHSCT without impairing the mobilization of peripheral blood progenitor cells (PBPC) or engraftment. Here we present interim safety and toxicity data from this ongoing trial (NCT03077828) including the yields of PBPC mobilization and engraftment. Methods: Enrollment criteria include patients age &gt;18 years medically fit for autoHSCT with relapsed/refractory cHL and excludes those with prior PD-1 inhibitor exposure, CNS involvement, more than 2 prior regimens or history of autoimmune disease. Patients are treated with 2 cycles of PEM 200 mg IV on day 1 in combination with ICE chemotherapy (ifosfamide 5000 mg/m2 day 2 CIV over 24hr, carboplatin AUC 5 IV day 2, etoposide 100 mg/m2 IV days 1-3) on a Q21 day cycle. PBPC mobilization and harvest are performed per institutional protocol on recovery post-cycle #2. A cycle of PEM 200 mg IV is then administered as monotherapy followed by response assessment with PET-CT. Patients with Deauville scores ≤3 proceed to autoHSCT per institutional protocol. A third cycle of PEM+ICE is optional following the PET-CT assessment. Neither the conditioning regimen nor management during transplantation is dictated by the protocol. Results: As of July 2019, 23 of 40 planned patients have evaluable safety and toxicity data. One patient had inconclusive pathology and was removed from study after one cycle of PEM-ICE but is included for this report. The median age was 32 (range 19-62) and 17 of 23 patients were females (74%). 8 patients were refractory to first-line therapy, and 9 relapsed within one year of treatment. 19 patients had received ABVD. Following protocol directed therapy, all but one patient had successful mobilization and collection; one had a severe allergic reaction to filgrastim and underwent bone marrow harvest instead. 16 patients collected in a single day of apheresis; the remainder collected within 4 days. The median number of stem cells harvested was 12.6 x 106 CD34+ cells/kg (range 4.2 - 46.1 x 106/kg). 3 patients underwent the 3rd cycle of PEM + ICE chemotherapy. 3 patients had Deauville scores &gt;3 on FDG-PET response assessment; two had biopsies showing only benign processes and proceeded to transplant. Following stem cell reinfusion, all patients successfully engrafted, with a median time to absolute neutrophil and platelet recovery of 11 days (range: 9 - 24) and 12 days (range: 9 - 23), respectively. The combination of PEM + ICE chemotherapy was well tolerated. There were no reports of pneumonitis, colitis, hepatitis, or endocrinopathies. The most common toxicities were cytopenias, mucositis, diarrhea and febrile neutropenia. A single death on protocol was deemed secondary to advanced cardiovascular disease discovered mid-treatment during the patient's pre-transplant assessment. There was no clinical evidence to suggest an inflammatory process resulting in the cardiac arrest. Conclusions: The combination of PEM with ICE chemotherapy in relapsed / refractory cHL appears tolerable and safe. We found no significant hindrance to peripheral blood stem cell harvest and PEM- related AEs were uncommon. Additionally, pre-treatment with a checkpoint inhibitor prior to autoHSCT appears safe thus far and does not appear to delay engraftment. Disclosures Casulo: Celgene: Research Funding; Gilead: Honoraria, Other: Travel, accommodation, expenses; Roche: Other: Travel, accommodation, expenses. Karmali:Takeda, BMS: Other: Research Funding to Institution; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Astrazeneca: Speakers Bureau. Pro:Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Kyowa Hakka Kirin: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Mehta:Millennium/Takeda, Celgene; stock in Celgene, Bristol-Myers Squibb and Bluebird: Speakers Bureau. Gordon:Bayer: Other: Advisory Board; Juno/Celgene: Other: Advisory Board, Research Funding; Gilead: Other: Advisory Board; Zylem LLC: Other: co-founder; research in nanoparticles in cancer. Winter:Merck: Consultancy, Research Funding.