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Background: The rate of osteoarthritis (OA) in patients with a history of previous anterior shoulder instability (ASI) varies within the literature, with the majority of studies investigating rates after surgical stabilization. ASI appears to lead to increased rates of OA, although risk factors for developing OA in cohorts treated nonoperatively and operatively are not well-defined. Purpose: To determine the incidence of clinically symptomatic OA and identify potential risk factors for the development of OA in patients younger than 40 years with a known history of ASI. Study Design: Case-control study; Level of evidence, 3. Methods: An established, geographically based database was used to identify patients in the United States who were younger than 40 years and were diagnosed with ASI between 1994 and 2014. Patient information, including demographic, imaging, and surgical details, was collected. Comparative analysis was performed between groups with and without OA at final follow-up as well as between patients who underwent surgical and nonsurgical management. Results: The study population consisted of 154 patients with a mean follow-up of 15.2 years (range, 5.1-29.8 years). The mean age at initial instability event was 20.9 years (95% CI, 19.9-22.0 years). Overall, 22.7% of patients developed clinically symptomatic glenohumeral OA. Multivariate analysis revealed that current or former smokers (odds ratio [OR], 4.3; 95% CI, 1.1-16.5; P = .030), hyperlaxity (OR, 10.1; 95% CI, 1.4-72.4; P = .020), laborer occupation (OR, 6.1; 95% CI, 1.02-36.1; P = .043), body mass index (BMI) (OR, 1.2; 95% CI, 1.03-1.3; P = .012), and age at initial instability (OR, 1.1; 95% CI, 1.02-1.2; P = .013) as potential independent risk factors when accounting for other demographic and clinical variables. Conclusion: In a US geographic population of patients younger than 40 years with ASI, approximately one-fourth of patients developed symptomatic OA at a mean follow-up of 15 years from their first instability event. When accounting for differences in patient demographic and clinical data, we noted a potentially increased risk for the development of OA in patients who are current or former smokers, have hyperlaxity, are laborers, have higher BMI, and have increased age at initial instability event. Smoking status, occupation, and BMI are modifiable factors that could potentially decrease risk for the development of symptomatic OA in these patients.

Background The relative benefits of haploidentical HCT using PTCy compared to traditional matched-sibling donor, traditional unrelated donor and umbilical cord blood (UCB) allogeneic HCT for adult acute lymphoblastic leukemia (ALL) is still being defined. Methods We performed a retrospective analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database comparing post-HCT outcomes of haploidentical donors with PTCy to HLA-identical sibling donors, 8/8 HLA-MUDs, 7/8 HLA-MUDs, and UCB. Outcomes were overall survival (OS) leukemia-free survival (LFS), relapse, non-relapse mortality (NRM), grade 2-4 and grade 3-4 acute graft-versus-host disease (aGVHD), and chronic GVHD (cGVHD). Eligible patients were adults with ALL in complete remission (CR1, CR2, or CR3) undergoing first allogeneic HCT from 2013 to 2017. Key exclusion included not receiving PTCy for haploidentical HCT and ex vivo T-cell depleted or CD34-selected grafts. Cox proportional hazards multivariable regression analysis was used to compare the treatment groups. Results 4201 patients were studied: 393 haploidentical donor (92 centers), 1627 HLA-identical sibling donor (206 centers), 1646 8/8 HLA-MUD (181 centers), 230 7/8 HLA-MUD (90 centers), and 305 UCB (79 centers). Groups were well matched, however, notable differences between included race, time from diagnosis to HCT (CR1 only), conditioning regimen intensity, donor age, graft source for non-cord (peripheral blood or bone marrow), GVHD prophylaxis modality, and the use of in vivo T-cell depletion. Compared to other groups, haploidentical HCT had the lowest percentage of non-Hispanic white patients (43% vs. 49-74%), was more likely to use reduced-intensity conditioning (42% vs 17-25%), and was more likely to use bone marrow (41% vs. 14-29%). In multivariate analysis comparing haploidentical to matched-sibling donor HCT, no differences were observed in OS, LFS, NRM, relapse, or aGVHD. Compared to haploidentical HCT, the risk of cGVHD was significantly higher with matched-sibling donor HCT (D/R sex match F/M, HR 2.59, P<0.001, D/R sex match, other, HR 1.37, P=0.003). Comparing haploidentical to 8/8 HLA-MUD HCT, no differences were seen in OS, LFS, relapse, or Grade 2-4 aGVHD but 8/8 HLA-MUD HCT was associated with increased incidences of NRM (HR 1.42, P=0.02), grade 3-4 aGVHD (HR 1.59, P=0.005), and cGVHD (HR D/R sex match F/M, HR 2.91, P<0.001, D/R sex match, other, HR 1.38, P=0.001). Comparing haploidentical to 7/8 HLA-MUD HCT, no differences were seen in LFS or relapse but 7/8 HLA-MUD HCT was associated with worse OS (HR 1.38, P=0.01) and increased incidences of NRM (HR 2.13, P=<0.001), grade 2-4 aGVHD (HR 1.33, P=0.04) , grade 3-4 aGVHD (HR 1.86, P=0.003), and cGVHD (HR 1.72, P=<0.001). Comparing haploidentical to UCB HCT, no differences were seen in late OS (>18 months), late LFS, relapse, or cGVHD. Compared to haploidentical HCT, UCB HCT was associated with worse early OS (≤18 months, HR 1.93, P<0.001), worse early LFS (HR 1.40, P=0.007) and increased incidences of NRM (HR 2.08, P<0.001), grade 2-4 aGVHD (HR 1.83, P<0.001), and grade 3-4 aGVHD (HR 1.97, P<0.001). Similar outcomes were observed in sensitivity analyses restricting cohorts to (1) MA conditioning with peripheral blood stem cells and (2) calcineurin inhibitor-based GVHD prophylaxis for matched-sibling, unrelated donor, and UCB HCT. Conclusions For OS and LFS, haploidentical HCT using PTCy for adult ALL was superior to traditional HCT using 7/8 HLA-MUDs and UCB but equivalent to traditional HCT using matched-sibling donors and 8/8 HLA-MUDs. Results were consistent across all subgroups. Haploidentical HCT had a lower incidence of aGVHD compared to 8/8 HLA-MUD, 7/8 HLA-MUD, and UCB HCT and a lower incidence of cGVHD compared to matched-sibling donor, 8/8 HLA-MUD, and 7/8 HLA-MUD HCT. Based on these data, haploidentical HCT with PTCy results in similar survival with less GVHD compared to traditional matched-sibling and 8/8 HLA-matched donor HCT and is the superior alternative donor option for adult patients with ALL needing allogeneic HCT in CR. Figure Disclosures Wieduwilt: Leadiant: Research Funding; Shire: Research Funding; Merck: Research Funding; Macrogeneics: Research Funding; Amgen: Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. de Lima:Incyte: Other: Personal Fees, advisory board; BMS: Other: Personal Fees, advisory board; Pfizer: Other: Personal fees, advisory board, Research Funding; Celgene: Research Funding; Kadmon: Other: Personal Fees, Advisory board. Kebriaei:Novartis: Other: Served on advisory board; Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Amgen: Other: Research Support; Jazz: Consultancy. Hourigan:Merck: Other: Research Support (CRADA); Sellas: Other: Research Support (CRADA). Weisdorf:FATE Therapeutics: Consultancy; Incyte: Research Funding.

Introduction: Failure to engraft donor cells is a devastating complication after allogeneic hematopoietic cell transplantation (HCT) while full engraftment remains a challenge in some recipients. Therapeutic approaches, such as recombinant hematopoietic growth factors, salvage only a minority of patients leaving affected patients at risk for recurrent infections and multiple blood products transfusions. PLX-R18 cells have been shown to mitigate bone marrow failure in rodent and non-human primate models. Further, these human placenta-derived mesenchymal-like adherent stromal cells secrete many cytokines after intramuscular (IM) injection that have been shown to stimulate growth and migration of bone marrow cells in vitro, e.g. MCP-1, IL-6, and IL-8. The initial results of the first cohort of this phase I trial were previously reported (ASH 2018 abstract 3379). Methods: Enrollment for this multi-center, open label, dose-escalation, phase I trial (ClinicalTrials.gov: NCT03002519) began in October 2017. Eligibility criteria included patients age ≥18 years who underwent either autologous (auto) or allogeneic (allo) HCT but suffered from incomplete hematopoietic recovery at least 3 months post-transplant, defined as failure to maintain either hemoglobin (Hb) >8g/dL and/or neutrophil count (ANC) >1,000/μL and/or platelet (PLT) count >50,000/μL. Other eligibility criteria included no evidence of underlying malignancy at time of enrollment, no active infection and no evidence of grade 3-4 acute or severe chronic GvHD. Subjects were enrolled into 3 dose-escalating cohorts: low-dose at 1M cells/kg (n=3), intermediate-dose at 2M cells/kg (n=6), and high-dose at 4M cells/kg (n=10). The specified dose of PLX-R18 cells was injected IM in multiple locations and given twice, 1 week apart. Cohorts were recruited sequentially, and progression to the next cohort was based on the safety assessment of its predecessor. Adverse event grading used the NCI CTCAE criteria. As of July 2020, all patients in cohorts 1 and 2 (3 & 6 patients, respectively) and 10 patients in cohort 3 were treated. Data were analyzed using the lmerTest package (ver. 3.1.0) in R (ver. 3.6.1) to produce baseline-adjusted least square means. As study is in progress and data collection ongoing, not all subjects have data on all parameters for all time points. Results: Data on 19 subjects (29-75 yrs) with either allo (n=17) or auto (n=2) HCT are reported herein. Not all patients reached the 9 month time point. Four patients died while on study and 2 withdrew consent within the 1 year follow up period. All deaths and other severe adverse events (SAEs) occurred due to progression of primary disease and were assessed as not related by investigators and sponsor. Most frequent related AEs were injection-site reactions. The table summarizes number of patients who improved from below the critical level, as defined above, at day 0 to above the critical level for a sustained period. Only those patients that were below the critical blood levels at day 0 are shown. To date, the majority of such patients improved to above the critical level after treatment. For example, 9 patients had ANC <1000/μL at day 0. Of the 4 patients for which data currently exists, all improved to ≥1000/μL at 9 months. The plots show changes in Hb, ANC and PLT up to 9 months following treatment. The dashed lines represent respective critical levels. Overall, there was improvement in the 3 parameters, with the greatest improvement observed in patients receiving the predicted optimal dose of 4M cells/kg. In this cohort, Hb levels increased from 9.29±0.5 to 13.19±1.2 (p=0.0019), ANC increased from 1.09±0.6 to 5.13±1.7 (p=0.018) and PLT increased from 45.7±10 to 175.9±28 (p=0.000012). Conclusions: Treatment with PLX-R18 is safe, well-tolerated and clearly effective in some patients. The most frequent AEs were reversible injection site reactions, all without sequelae. An overall improvement was observed in most patients, and among the high-dose cohort clinically impressive improvements in Hb, ANC and PLT were observed. The trial continues to follow up on patients. Upon completion, a large phase II trial, using the optimal dose, is considered for the same indication. Other attractive clinical areas for PLX-R18 therapy include acute radiation syndrome, bone marrow failure, aplastic anemia, myelofibrosis and with HCT as a "pan" cytokine to enhance rapid count recovery in all cells lines. Figure Disclosures Lazarus: Pluristem ltd: Consultancy. McGuirk:Astellas: Research Funding; Bellicum Pharmaceutical: Research Funding; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Allo Vir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Rowley:AbbVie: Current equity holder in publicly-traded company; FATE Therapeutics: Consultancy. Ofir:Pluristem: Current Employment. Shani:Pluristem ltd: Current Employment. Rowe:Pluristem ltd: Consultancy.

Purpose To compare the (1) rates of complications and reoperations, (2) rate of anterior cruciate ligament (ACL) graft failure, and (3) patient‐reported outcomes (PROs) among patients after hamstring autograft ACL reconstruction (ACLR) with and without independent suture tape reinforcement at a minimum 2‐year clinical follow‐up. Methods We performed a 1:2 matched‐cohort comparison of patients who underwent hamstring autograft ACLR with and without independent suture tape reinforcement between July 2011 and July 2017. Patients were matched according to age, sex, body mass index, preinjury Tegner activity score, and concomitant meniscal injury. Medical records were reviewed for demographic characteristics, additional injuries, and concomitant procedures. PRO scores (including Tegner activity, Lysholm, and International Knee Documentation Committee scores) and physical examination findings were collected both preoperatively and at a minimum of 2 years postoperatively. Results Overall, 108 patients who underwent ACLR were included: 36 patients (mean age, 25.3 years; range, 13‐44 years) with independent suture tape reinforcement and 72 patients (mean age, 24.9 years; range, 13‐54 years) without suture tape reinforcement. Overall, 5 of 36 suture tape patients (14%) and 10 of 72 control patients (14%) underwent reoperations. At an average follow‐up of 26.1 months in the suture tape cohort and 31.3 months in the control cohort, 1 patient in the suture tape cohort and 4 patients in the control cohort experienced graft failure. There were no statistically significant differences between the suture tape and control groups regarding return‐to‐sport rate (89% and 88%, respectively), postoperative International Knee Documentation Committee score (94.4 and 93.8, respectively), and postoperative Lysholm score (95.6 and 94, respectively). There was a statistically significant difference between the suture tape and control groups in postoperative Tegner activity score, at 7.1 (95% confidence interval, 6.5‐7.6) and 6.4 (95% confidence interval, 6.2‐6.6), respectively ( P = .026). Conclusions ACLR with hamstring autograft and independent suture tape reinforcement was performed safely with low rates of complications, graft failure, and reoperations with similar PROs, function, and return‐to‐sport rates when compared with hamstring autograft ACLR without suture tape reinforcement at a minimum 2‐year follow‐up. Level of Evidence Level III, retrospective comparative study.

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

Background: Femoroacetabular impingement (FAI) is a common cause of hip pain and a known risk factor for hip osteoarthritis (OA) and total hip arthroplasty (THA) at a young age. Unfortunately, little is known about the specific factors associated with an increased risk of OA. Purpose: To (1) report the overall rate of symptomatic hip OA and/or THA in patients with FAI without surgical intervention and (2) identify radiographic features and patient characteristics associated with hip OA. Study Design: Case-control study; Level of evidence, 3. Methods: A geographic database was used to identify all patients with hip pain and radiographs between 2000 and 2016. Chart review was performed to identify patients with FAI. Patient medical records were reviewed to obtain demographic information, clinical history, physical examination findings, imaging details, and treatment details. Kaplan-Meier analysis was used to determine the rate of hip OA. Univariate and multivariate proportional hazard regression models were performed to determine risk factors for OA. Results: The study included 952 patients (649 female; 303 male; 1104 total hips) with FAI. The majority of hips had mixed type (n = 785; 71.1%), 211 (19.1%) had pincer type, and 108 (9.8%) had cam type. Mean age at time of presentation was 27.6 ± 8.7 years. Mean follow-up time was 24.7 ± 12.5 years. The rate of OA was 13.5%. THA was performed in 4% of patients. Male sex, body mass index (BMI) greater than 29, and increased age were risk factors for OA (male sex: hazard ratio [HR], 2.28; P < .01; BMI >29: HR, 2.11; P < .01; per year of increased age: HR, 1.11; P < .01.). Smoking and diabetes mellitus were not significant risk factors. No radiographic morphological features were found to be significant risk factors for OA. Conclusion: At mean follow-up of 24.7 years, 14% of hips had symptomatic OA and 4% underwent THA. BMI greater than 29, male sex, and increased age at the time of presentation with hip pain were risk factors for hip OA. The cohort consisted of a large percentage of mixed-type FAI morphologies, and no specific radiographic risk factors for OA were identified.

Objectives: There remains a paucity of data describing the efficacy of non-operative treatment following an index anterior instability event. The purpose of this study was to describe the long-term outcomes of non-operative treatment following index anterior instability event, define the success rate of initial non-operative treatment for anterior shoulder instability, and describe factors that predict conversion to surgery after initial non-operative management to help guide surgical decision making in these patients. Methods: An established geographic database was utilized to identify patients under the age of 40 treated for anterior shoulder instability between 1994 and 2016. Patient demographics, comorbidities, injury characteristics, instability history, activity level, x-rays, advanced imaging, treatment course, and outcomes were evaluated. Patients treated non-operatively for the first 6 months following index instability event were analyzed to determine long-term outcomes, success rate of continued non-operative treatment, and factors associated with conversion to surgery. Results: 739 patients met criteria with an average follow-up of 190 months (range 0.13 to 490 months). Average age was 23.8, mean BMI was 25.6, 9.1% had a history of hyperlaxity, and 83.9% of instability events were due to trauma. 29.7% of patients had a Hill-Sachs lesion on index x-ray, and 6.3% had a bony Bankart. 198 shoulders went on to operative treatment (26.8%) with a mean time to surgery of 62.7 months following initial instability event. At final follow-up, 24.0% reported mild pain, 6.2% as moderate, 0.2% as severe. 13.8% of patients had evidence of glenohumeral arthritis on final follow-up x-rays compared to 1.6% on initial radiographs. Factors associated with conversion to surgery included 2 or more dislocations prior to first clinical evaluation (OR=1.75, p<0.001), labor intense occupation (OR=1.49, p=0.031), Hill Sachs lesion on index x-ray (OR=1.31, p=0.034), and MRI findings including: anteroinferior labral tear (OR=2.15, p<0.001), posteroinferior labral tear (OR=1.38, p=0.049), SLAP tear (OR=1.29, p=0.054), Hill-Sachs lesion (OR=1.85, p<0.001), and glenohumeral cartilage injury (OR=1.26, p=0.041). Conclusion: The majority of patients less than 40 can be definitively treated non-operatively after an initial 6 month episode of non-operative treatment. A small proportion will report pain over the long-term and/or develop glenohumeral arthritis. Multiple factors upon initial evaluation were associated with future conversion to surgery including: increasing number of prior instability events, occupation, and degree of soft tissue injury on MRI.

Objectives: The rate of osteoarthritis (OA) in patients with anterior shoulder instability (ASI) varies within the literature, with the majority of studies investigating rates after surgical stabilization. ASI appears to lead to increased rates of OA, although risk factors for developing OA in non-operative and operative cohorts are not well defined. The purpose of this study was to determine the incidence of clinically symptomatic OA and identify potential risk factors for the development of OA following ASI in a U.S. geographic population of patients under the age of 40. Methods: An established geographic database was used to identify patients less than 40 years old diagnosed with anterior should instability between 1994 and 2016. Patient information, including demographics, imaging and surgical details, was collected and comparative analysis was performed between groups with and without OA at final follow-up, as well as patients who underwent surgical and non-surgical management. Results: The study population consisted of 154 patients with a mean follow-up of 15.2 years (range 5.1-29.8). Overall, 22.7% of patients developed clinically symptomatic glenohumeral OA. Twenty-eight percent of patients who underwent at least 1 surgical intervention and 17% of patients who underwent non-operative management of anterior shoulder instability developed glenohumeral OA (p=0.176). Patients who developed arthritis were older at initial instability event (p=0.002) and had higher BMI (p=0.007). Additionally, patients with OA were more likely to be current or former smokers (p=0.004), have a seizure disorder (p=0.033), and be manual laborers (p=0.044). Risk factors for developing OA included seizure disorders (RR 2.61, 95 % CI 1.34-5.07), cartilage injury on initial MRI (RR 2.48, (1.00-6.13), current or former smoker (RR 2.46, 95% CI 1.37-4.42), laborer occupation (RR 2.14, 95% CI 1.14-4.01), and age at initial instability event (OR 1.09 per year, 95% 1.03-1.17). Athletes (RR 0.51, 95% CI 1.08-3.54), specifically contact athletes at the time of initial instability (RR 0.45, 95% CI 0.21-0.97), were less likely to develop OA. There was no difference in the number of dislocations or number of instability events in patients with and without symptomatic osteoarthritis. Conclusions: In a U.S. geographic population of patients less than 40 years old with ASI, approximately one-fourth of patients developed symptomatic OA at a mean follow-up of 15 years from their first instability event. When accounting for differences in patient demographics, there was no significant difference in the rates of OA in patients who underwent surgical and non-surgical management. Overall, there was an increased risk for the development of OA in patients with seizure disorders, cartilage injury on initial MRI, current or former smokers, laborer occupation and increased age at the initial instability event.

Objective: To evaluate the incidence of and characterize the presentation of neuropsychiatric symptoms and/or Parkinsonism as a presentation of central nervous system lymphoma (CNSL) in either its primary CNSL form or when it spreads to the brain in systemic diffuse large B-cell lymphoma (secondary CNSL). Patients and Methods: With Institutional Review Board approval we identified patients who had been treated at Mayo Clinic from 1998 to 2018 and were recorded to have a combination of ICD 9/10 codes for CNSL and various psychiatric diagnoses. Results: A total of 20 of the 232 patients (9%) were noted to have neuropsychiatric symptoms preceding diagnosis. The average age at diagnosis was 62, with even split for sex. The majority (85%) of patients had primary CNSL. The average duration of symptoms before the diagnosis was 4.8 months. Confusion (80%), depression (40%), apathy (30%), anxiety (30%), and agitation (30%) were the most common symptoms identified. The majority (65%) of patients had subcortical lesions followed by the frontal lobe (50%). Parkinsonism was identified in 5 of the 20 patients with 4 demonstrating resolution of symptoms with treatment of the lymphoma. Conclusions: Neuropsychiatric symptoms are a rare but notable symptom before the presentation of CNSL. There is an increasing awareness of neurological illness presenting as pure psychiatric disturbance, prompting the need to exclude organic and treatable diseases, particularly in elderly patients. Acknowledgment and diagnosis are important for an appropriate management as there is a significant impact on patient and caregiver quality of life.