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Abstract Abstract 3701 Background: Salvage chemotherapy and autologous stem cell transplantation (ASCT) in the management of relapsed or refractory Hodgkin's lymphoma (HL) results in prolonged disease-free survival in only around 50% of patients (pts). Median survival following relapse from ASCT is estimated at 2.4 years, with poor outcomes in those experiencing relapse or progressive disease within one year from ASCT (Horning 2008 et al). Recently, a pivotal multicenter Phase 2 trial investigated the efficacy of brentuximab vedotin (BV) in pts with recurrent HL following ASCT. The study demonstrated an overall response rate of 75% and median duration of response of 6.7 months. Furthermore, 34% of patients achieved a complete response (CR), with a median progression free survival of 29 months (mos). Whether treatment with BV renders an OS benefit in pts with relapsed or refractory disease after ASCT remains to be determined. Objective: 1) To compare OS in pts with relapsed HL after receiving ASCT in a cohort of 102 HL pts treated with BV, with 756 pts from 6 international centers before the introduction of BV. 2) To evaluate predictors of durable CR in pts treated with BV. Methods: Kaplan-Meier method was used to depict time-to-event outcomes, including OS. The Chi-square test was used to evaluate the association between two categorical variables and log-rank test to compare time-to-event endpoints among pt groups. Based on the univariate proportional hazard model, we examined whether certain variables (sex, stage at diagnosis, number of prior treatments, and time to CR) were predictors of CR duration in pts receiving BV. Results: In the non-randomized comparison between those with relapsed-refractory HL following ASCT who received BV and those who did not, pts were well matched by age, with a relatively higher percentage of females treated on the pivotal study. Dates of progression from ASCT ranged from 1996–2009 in the BV group and 1981–2003 in the international cohort. Median follow-up after ASCT for the censored observations of pts who received BV and those in the international cohort was 49.4 and 58.8 mos. The difference in median OS was statistically significant (p<0.0001) between those receiving BV and those not exposed to the drug (91.49 vs. 27.99 mos). Improvement in OS was irrespective of time to relapse from ASCT, despite previous studies noting a higher risk of recurrence in pts relapsing within 12 mos of ASCT (Sureda 2005 et al). Neither age nor sex was found to impact OS. In the subgroup analysis of pts achieving a CR with BV, univariate analysis of duration of CR and PFS uncovered no significant factors, while only stage of disease at initial diagnosis had a significant effect on OS (P=0.0004). Disease status characterized as relapsed vs. refractory had borderline significance with a positive impact on OS (P=0.0581). No significant associations were noted between the variables and duration of response post BV stratified into periods of less or greater than 12 mos. However, among those pts who experienced a duration of CR greater than 12 mos, 81.8% (n=18) had an initial CR after receiving ≤ 4 doses of BV, compared with 58.3% entering CR after receiving > 4 doses. Conclusions: While the impact of BV on OS can only be determined through a randomized clinical trial, our analysis indicated that treatment with BV in pts with relapsed/refractory HL following ASCT is associated with prolonged OS when compared with historical control patients. Those who achieve a rapid CR with BV may also have a longer duration of response. A randomized clinical trial is ongoing to evaluate prospectively the efficacy of BV following ASCT. Disclosures: Chen: Seattle Genetics, Inc.: Consultancy, Research Funding, Speakers Bureau. Gopal:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Ansell:Seattle Genetics, Inc.: Research Funding; Celgene: Consultancy. Savage:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Ramchandren:Seattle Genetics, Inc.: Speakers Bureau. Forero-Torres:Seattle Genetics: Research Funding. Moskowitz:Seattle Genetics: Speakers Bureau. Connors:Seattle Genetics, Inc.: Research Funding. de Vos:Seattle Genetics: Speakers Bureau. Engert:Takeda: Honoraria, Research Funding; Millennium: Honoraria, Research Funding. Illidge:Seattle Genetics, Inc.: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Honoraria. Morschhauser:Takeda: Honoraria. Younes:Seattle Genetics: Honoraria.

Abstract Background Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by erythrocytosis, splenomegaly and a frequently burdensome symptom profile. Despite current guidelines of aspirin, phlebotomy, and selective cytoreduction, many patients have inadequately controlled PV-related symptoms and/or disease features. We performed a comparison of PV symptom burden/disease feature phenotypes to understand unmet needs in current medical management. Methods Data was collected prospectively amongst an international cohort of PV patients including symptom burden, demographics, and disease features. Subgroups were identified who had previously failed hydroxyurea (PV-HU), required ongoing phlebotomy (PV-P), had palpable splenomegaly (PV-S), or had all 3 features (PV-HUPS). Control groups were derived from the remaining PV patients lacking the specified subgroup trait; patients in whom the trait status was unknown were excluded from each respective control group. All participants completed the MPN specific symptom burden questionnaire (MPN-SAF TSS (MPN-10 – Table 1)) and had no prior history of splenectomy. Surveyed symptoms on the MPN-10 included the patient's perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. PV risk scores were calculated using the 2013 criteria (Leukemia 2013). Comparison of symptoms between groups employed t-tests. Results Patient Demographics and Disease Features Between Phenotypic Groups A total of 1334 PV patients completed the MPN-10, and were assigned to categories of PV-HU (499 [37%]), PV-P (646 [48%]), PV-S (369, [28%]), and PV-HUPS (148 [12%]). The demographics between these groups were similar (comparable age (median range 60-63), PV risk scores (mean risk range: Low 16.4-23.7%; Intermediate 31.4%-36.6%; High 42.8%-47%). Mean hemoglobin was similar among PV subgroups (range 14.4-14.9); PV-HUPS had a higher mean WBC count (20.3 g/dL vs. 8.8-11.8 g/dL) and platelet count (703.5 x 10(9)/L vs. 327.5-462.8 x 10(9)/L), and disease duration (11.5 years vs. 6.4-8.8 years). Prior thrombosis was most common in PV-S patients (28.5% vs. 21.8-25.2%) and prior hemorrhage was most common in PV-HUPS patients (23.8% vs. 13.7-15.8%). Symptom Burden The MPN-10 scores of each problematic PV phenotype (HU, P, S, HUPS) were compared to the remainder of the PV cohort lacking the trait (PV-control; Table 1). Both individual symptom scores and TSS were highest for PV-HUPS patients (mean TSS 32.5 vs. 27.7-29.2). All problematic PV subgroups demonstrated significant differences for individual symptoms and TSS compared to PV-control. Comparing "problematic" subgroup responses, PV-HU patients described more inactivity whereas PV-S patients described more early satiety and pruritus. No statistical differences were noted in PV-HU, PV-P and PV-HUPS patient responses to MPN-10 items of "fever" and "weight loss". Discussion PV patients who have either failed HU, are undergoing phlebotomy and/or have splenomegaly exhibit moderate to severe symptomatology and demonstrate unmet medical need for management. As evidenced in this study, considerable overlap in symptomatology exists in PV-HU, PV-P, PV-S and PV-HUPS. Current randomized trials of JAK inhibitors have demonstrated benefits in a PV-HUPS phenotype. This data suggests that PV patients with any evidence of inadequate control (PV-HU, P, or S) have similarly unmet needs and may be candidates for clinical trials, intensification of medical therapy or perhaps JAK inhibitor therapy. Disclosures Kiladjian: Shire Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zweegman:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding. Besses:Shire Pharmaceuticals: honoraria for educational lectures Other. Birgegard:Shire Pharmaceuticals: Consultancy, Honoraria, Research Funding. Etienne:Novartis, BMS, Pfizer, Ariad: Honoraria. Roy:Merck: Peg-Interferon provided for academic clinical trial in CML Other. te Boekhorst:Novartis: Consultancy. Griesshammer:Novartis: Honoraria; Shire: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Roche: Honoraria. Mesa:Incyte Corporation, CTI, NPS Pharma, Inc., Gilead Science Inc., Celgene: Research Funding.

Abstract Abstract 591 Background: Survival of patients with MM has improved over the past two decades, in part due to the use of AHCT. Increasingly, second primary malignancies (SPMs) are observed in MM survivors. Determining the baseline incidence and risk factors associated with SPMs after AHCT is important to assess risk and to evaluate the risk-benefit ratio of newer therapies. Methods: We analyzed the incidence of SPMs in 3784 MM patients receiving (“upfront”) AHCT for MM within 18 months of diagnosis between 1990 and 2010 and reported to the CIBMTR. Cumulative incidence rates of SPMs were estimated taking into account the competing risk of death. For each transplant recipient, the number of person-years at risk was calculated from the date of transplantation until date of last contact, death, or diagnosis of SPM, whichever occurred first. Incidence rates for all invasive cancers in the general population were obtained from the SEER database. Age-, sex-, and race- specific incidence rates for overall SPMs and particular anatomical sites were applied to the appropriate person-years at risk to compute the expected numbers of cancers. Observed–to –expected (O/E) ratios were calculated, and Poisson distribution 99% confidence intervals (CIs) were generated. Poisson regression model was used to analyze risk factors for overall SPMs and AML/MDS. Results: Pre-transplant therapy included novel agents in 56% including thalidomide (35%), lenalidomide (9%), bortezomib (16%) or their combinations (11%). Majority (80%) received high dose melphalan conditioning. Post-transplant maintenance therapy included thalidomide (16%), lenalidomide (8%), bortezomib (9%) and interferon (6%). Median follow-up of survivors was 52 months (range 3 to 192 months).With 12707 person years of follow up, 153 new malignancies were reported with a crude rate of 1.2 SPM per 100 person years of follow up. Observed/Expected [O/E] ratio for all SPMs was 0.99 (99% CI, 0.80–1.22). Cumulative incidence of SPM overall was 2.48% (95% CI, 1.96–3.05) at 3 years and 6.0% (95% CI, 4.96–7.10) at 7 years [Figure 1]. Individual SPMs observed significantly more frequently than expected are summarized in Table 1. The cumulative incidence of MDS/AML was 0.5% (95% CI, 0.28–0.78) at 3 years and 1.3 (95% CI, 0.85– 1.9%) at 7 years. Majority had MM progression prior to diagnosis of SPM (65 of 102 patients overall and 15 of 23 patients for MDS/AML). In multivariate analysis, significant risk factors for development of SPMs included: obesity [Hazard ratio = HR 1.89(95%CI, 1.21–2.93), p=0.0047 for BMI>30 vs. BMI<25], older age: [HR10.53 (95%CI, 1.46–75.82), p=0.0195] for 60–69 year olds and HR14.4 (95%CI, 1.89–109.75), p=0.01 for 70+ year olds compared to the 18–39 year old group. Specific conditioning regimens did not correlate with the risk of SPM. The low number of MDS/AML (33 events out of 3784 cases) limited the power of multivariate analysis. Increasing age was significantly associated with development of MDS (HR10.77, (95%CI,92.09–55.51), p=0.004 for 70+ year old vs. 40–49 year olds). Conclusion: In this large cohort of AHCT recipients for MM, the incidence of MDS/AML, melanoma and other skin cancers was significantly higher compared to age and sex matched general population. However the overall risk of SPM was similar to that expected for age and sex matched population. It was also similar to the placebo arms of recent reports by McCarthy Pl et al and Attal M et al (N Engl J Med. 10; 366(19):1770–91). Lenalidomide (8%) or thalidomide maintenance (16%) used in a small subset of patients with comparatively short follow up, was not associated with risk of SPM in the analysis of the overall cohort. Disclosures: Gale: Celgene: Employment. Brandenburg:Celgene: Employment, Equity Ownership. Lonial:Millennium, Celgene, Novartis, BMS, Onyx, Merck all Consultancy. Krishnan:Celgene and Millennium: Consultancy, Speakers Bureau. Dispenzieri:Celgene and Millennium: Research Funding. Hari:Celgene: Consultancy, Honoraria.

This prospective cohort study aimed to improve hospital outcomes through geographic location of hospitalist patients and conducting daily multidisciplinary team rounds—Goal-directed Achievements through Geographic Location (GAGL). Patients were admitted to a geographic (GAGL) study unit where daily multidisciplinary rounds took place among nursing, case management, a hospitalist, pharmacy, physical and occupational therapy, respiratory therapy, and nutrition services. A total of 985 (56.4%) patients were admitted to the GAGL study unit and 760 patients (43.6%) were admitted to non-GAGL units. Patients admitted to the GAGL study unit had a shorter average length of stay (3.64 days vs 4.35 days, P = .0001) and a lower number of risk events (91 [9.2%] vs 93 [12.2%], P = .038). There was no significant difference in 30-day readmissions, avoidable day events, or code blue team activations. GAGL provides a framework for hospital organizations to improve provider communication, hospital efficiency, and patient safety.

BACKGROUNDAndrogenic alopecia (AGA) is a common hair loss disorder. Studies have demonstrated successful treatment with platelet-rich plasma (PRP) in men, but studies in women are few.OBJECTIVETo evaluate PRP in the treatment of AGA in women, compared with topical minoxidil.MATERIALS AND METHODSTwenty women with AGA received topical minoxidil for 12 weeks and injectable PRP for 12 weeks in a randomized crossover design with an 8-week washout between treatments. Standardized TrichoScan analysis and quality-of-life questionnaires were assessed at baseline and 12-week follow-up for each treatment.RESULTSAfter PRP, significant increases from baseline to Week 12 in TrichoScan analysis hair count (p= .002) and vellus hair density (p= .009) occurred. However, minoxidil resulted in significant increases in hair count (p< .001), vellus hair density (p= .03), terminal hair density (p= .004), and cumulative thickness (p= .004). Several quality of life responses improved from baseline to Week 12 after PRP treatment, whereas no improvements were noted after minoxidil.CONCLUSIONPlatelet-rich plasma is an effective treatment for hair regrowth in female AGA, although not as effective as minoxidil. However, the improved quality of life responses after PRP, but not minoxidil, suggest a potential overall greater degree of satisfaction with PRP.LEVELS OF EVIDENCEI.CLINICAL TRIAL REGISTRATIONNCT03488108.

Background: As the incidence of ulnar collateral ligament (UCL) surgery continues to rise rapidly, an update on the current prevalence and demographics in professional baseball players is warranted. Hypothesis: The prevalence of UCL reconstruction in Major League Baseball (MLB) and Minor League Baseball (MiLB) players will be higher than that previously reported, and the increase in prevalence will be most notable in MiLB pitchers. Study Design: Cross-sectional study; Level of evidence, 3. Methods: During the 2018 baseball season, an online questionnaire regarding a history of UCL surgery was distributed to the certified athletic trainers of all 30 MLB organizations. These trainers then administered the survey to all players within their organizations, including MLB, MiLB (AAA, AA, High A, Low A, High Rookie, Low Rookie), and Dominican Summer League (DSL) players. Demographics were compared between MLB, MiLB, and DSL players. Results of this 2018 survey were compared with previously published data from the 2012 season to assess the change over time. Results: There were 6135 professional baseball players who completed the survey (66% response rate). The prevalence of UCL reconstruction in all MLB and MiLB players was 13% (637/4928), while the prevalence in DSL players was 2% (20/1207) ( P < .001). The prevalence in all MLB and MiLB players (13%) and pitchers (20%) both increased significantly from 2012 ( P < .001). MLB pitchers reported a higher prevalence of UCL reconstruction than did MiLB pitchers (26% vs 19%, respectively; P < .001). In 2018, the prevalence of UCL reconstruction has increased significantly in MiLB pitchers (19% vs 15%, respectively; P < .001) and pitchers aged 21 to 30 years (22% vs 17%, respectively; P < .001) compared with 2012. Additionally, United States–born pitchers were more likely to have undergone UCL reconstruction compared with Latin America–born pitchers (23% vs 13%, respectively; P < .001). Conclusion: The prevalence of UCL reconstruction has increased significantly in professional baseball players over the past 6 years from 10% to 13%. Ultimately, the prevalence of UCL reconstruction has increased most significantly since 2012 in MiLB pitchers, pitchers aged 21 to 30 years, and pitchers born in the United States.

ABSTRACT Cell-based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell-based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web-based marketing and patient testimonials supporting cell-based therapy. Both the American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) are committed to ensuring that the potential of cell-based therapies is realized through rigorous, reproducible, and clinically meaningful scientific discovery. The two organizations convened a multidisciplinary and international Task Force composed of physicians, surgeons, and scientists who are recognized experts in the development and use of cell-based therapies. The Task Force was charged with defining the state-of-the art in cell-based therapies and identifying the gaps in knowledge and methodologies that should guide the research agenda. The efforts of this Task Force are designed to provide researchers and clinicians with a better understanding of the current state of the science and research needed to advance the study and use of cell-based therapies for skeletal tissues. The design and implementation of rigorous, thorough protocols will be critical to leveraging these innovative treatments and optimizing clinical and functional patient outcomes. In addition to providing specific recommendations and ethical considerations for preclinical and clinical investigations, this report concludes with an outline to address knowledge gaps in how to determine the cell autonomous and nonautonomous effects of a donor population used for bone regeneration. © 2019 American Society for Bone and Mineral Research.

Gender bias and discrimination have profound and far-reaching effects on the health care workforce, delivery of patient care, and advancement of science and are antithetical to the principles of professionalism. In the quest for gender equity, medicine, with its abundance of highly educated and qualified women, should be leading the way. The sheer number of women who comprise the majority of pediatricians in the United States suggests this specialty has a unique opportunity to stand out as progressively equitable. Indeed, there has been much progress to celebrate for women in medicine and pediatrics. However, many challenges remain, and there are areas in which progress is too slow, stalled, or even regressing. The fair treatment of women pediatricians will require enhanced and simultaneous commitment from leaders in 4 key gatekeeper groups: academic medical centers, hospitals, health care organizations, and practices; medical societies; journals; and funding agencies. In this report, we describe the 6-step equity, diversity, and inclusion cycle, which provides a strategic methodology to (1) examine equity, diversity, and inclusion data; (2) share results with stakeholders; (3) investigate causality; (4) implement strategic interventions; (5) track outcomes and adjust strategies; and (6) disseminate results. Next steps include the enforcement of a climate of transparency and accountability, with leaders prioritizing and financially supporting workforce gender equity. This scientific and data-driven approach will accelerate progress and help pave a pathway to better health care and science.

AbstractBackgroundAn internal risk stratification algorithm was developed to decrease the risk of major adverse cardiac events (MACEs) during lead extractions (LEs).ObjectiveTo report upon the impact of a risk stratification algorithm (RISE [RIsk Stratification prior to lead Extraction] protocol) on outcomes of LEs in a high‐volume center.MethodsA retrospective review of a prospectively maintained LEs database was performed to identify features associated with MACEs. On the basis of the retrospective data, the RISE protocol differentiated LEs procedures into “High” and “Low” risk for occurrence of MACEs. High‐risk LEs included dual‐coil defibrillator lead (≥3 years), pacemaker and single‐coil lead (≥5 years), and any StarFix coronary sinus lead. During the prospective evaluation of the RISE protocol, “High‐risk” LEs were performed in an operating room (OR) or hybrid laboratory with the cardiac anesthesiologist, OR nursing team, perfusionist in the room, and a cardiac surgeon on the premises. “Low‐risk” LEs were performed in the electrophysiology (EP) laboratory with anesthesia provided by EP nursing team. The preintervention (pre‐RISE) and postintervention (post‐RISE) group spanned 19 and 40 months and consisted of 449 (632 leads) and 751 patients (1055 leads), respectively. The primary outcome of MACEs in the two groups was compared.ResultsProtocol compliance was 100%. The primary outcome of MACEs occurred in 15 patients (3.34%) before and 12 (1.6%) after implementation of the RISE protocol (P = .04).ConclusionRISE identified a low‐risk group where minimal resources are needed and allowed for rapid intervention in the high‐risk group that reduced the consequences of MACEs.