Citations

Abstract Objective Social determinants of health (SDoH) are nonclinical dispositions that impact patient health risks and clinical outcomes. Leveraging SDoH in clinical decision-making can potentially improve diagnosis, treatment planning, and patient outcomes. Despite increased interest in capturing SDoH in electronic health records (EHRs), such information is typically locked in unstructured clinical notes. Natural language processing (NLP) is the key technology to extract SDoH information from clinical text and expand its utility in patient care and research. This article presents a systematic review of the state-of-the-art NLP approaches and tools that focus on identifying and extracting SDoH data from unstructured clinical text in EHRs. Materials and Methods A broad literature search was conducted in February 2021 using 3 scholarly databases (ACL Anthology, PubMed, and Scopus) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 6402 publications were initially identified, and after applying the study inclusion criteria, 82 publications were selected for the final review. Results Smoking status (n = 27), substance use (n = 21), homelessness (n = 20), and alcohol use (n = 15) are the most frequently studied SDoH categories. Homelessness (n = 7) and other less-studied SDoH (eg, education, financial problems, social isolation and support, family problems) are mostly identified using rule-based approaches. In contrast, machine learning approaches are popular for identifying smoking status (n = 13), substance use (n = 9), and alcohol use (n = 9). Conclusion NLP offers significant potential to extract SDoH data from narrative clinical notes, which in turn can aid in the development of screening tools, risk prediction models, and clinical decision support systems.

SummaryInstitutional database search (1999–2020) for acute myeloid leukaemia (AML) identified 109 cases of myeloid sarcoma (MS), of which 19 were isolated and presented de novo. The latter displayed longer survival (median 78 months), compared to MS with synchronous intramedullary AML (n = 32; median 16 months) and de novo AML without MS (n = 729; median 22 months; P = 0·13). However, the difference in survival was no longer apparent after accounting for bone marrow cytogenetic risk status (P = 0·67). Treatment‐induced MS tumour resolution was not affected by the presence of intramedullary disease (P = 0·61). The current study clarifies the prognosis of de novo isolated MS, in the context of AML.

SummaryRuxolitinib for steroid‐refractory acute graft‐versus‐host disease (SR‐aGVHD) results in resistance or intolerance in 1/5 of patients. Outcomes of such patients are undefined. We identified these patients in a multicentre review and reported outcomes. Ruxolitinib‐resistant aGVHD was identified in 48/307 patients. Among patients receiving additional therapy, the overall response rate to next therapy was 36%. Median survival was 21 days. Ruxolitinib intolerance led to treatment discontinuation in 16/307 patients. Ten intolerant patients received additional therapy with 50% experiencing continued improvement of aGVHD. Median survival was 50 days in these patients. These data serve as a baseline for future SR‐aGVHD studies.

e20000 Background: In the novel agents’ era, refractoriness to induction in Multiple Myeloma (MM) is relatively rare. This population remain an unmet need and are often excluded from clinical trials. In the current era, chemotherapy-induced stem cell collections are used at Mayo Clinic in “poor responders” to induction, such as patients that progress prior to ASCT or patients with significant disease burden after induction. Methods: This is a retrospective study that includes all MM patients the underwent chemo-mobilization between January 2012 and September 2020 at Mayo Clinic. We compared our cohort to a cohort of 125 matched patients that were transplanted over the same time period and underwent mobilization with G-CSF and “on-demand” plerixafor. We matched the cohorts by level of response by IMWG at pre-transplant evaluation. Results: 125 newly diagnosed MM patients who received novel agents’ induction and had a poor response to induction were mobilized using IV intermediate-dose cyclophosphamide (83%) or VDT-PACE (17%) plus G-CSF and “on-demand” plerixafor. The median PFS and OS of the chemo-mobilized cohort were 16 months (95% CI 11-20) and 47 months (95% CI 37-71), respectively. Patients receiving chemo-mobilization had higher stem cell yields than the growth factor only cohort (median 9.88X106 cells/kg versus median 8.77X106 cells/kg, respectively (P<0.001)). The safety profile of chemo-mobilization was favorable, with no difference between the two groups in length of hospitalization during ASCT (P=0.95), days to neutrophil or platelet engraftment, and risk of bacteremia (P=0.38). 29% of the chemo-mobilized cohort and 66% of the matched cohort required plerixafor for adequate mobilization (P<0.001). Conclusions: Chemo-mobilization enhances stem cell collection in MM patients with a suboptimal response to induction and reduces the need for plerixafor without adversely impacting the post-transplant clinical course. [Table: see text]

7022 Background: Philadelphia-like Acute Lymphoblastic Leukemia (Ph-like ALL) is a high-risk subset of adult ALL. Until recently, there has not been a systematic platform to recognize this entity in clinical practice. Furthermore, data regarding the role of allogeneic hematopoietic cell transplantation (allo-HCT) is lacking. We conducted this study to identify patients with Ph-like ALL and describe their outcomes in comparison to Ph+ and Ph- ALL with emphasis on the role of allo-HCT. Methods: To identify cases of Ph-like ALL, available diagnostic cytogenetic pellets for patients in the Mayo Clinic ALL cohort (N=365) were tested using a targeted fluorescence in situ hybridization (FISH) panel developed by the Mayo Clinic Genomics Laboratory and includes probes to detect Ph-like-specific rearrangements (i.e., ABL1, ABL2, PDGFRB, JAK2 and CRLF2). Results: Thirty-three (9%) patients with Ph-like ALL were identified, the remaining patients were classified as Ph+ (N=132, 36%) or Ph- ALL (N=200, 55%). Patients with Ph-like ALL were younger (Median: 39 vs. 50 vs. 49 years, P=.01), had higher WBC (Median: 27.9 vs. 21.5 vs. 4.5 x109/L, P<.001), were less likely to achieve CR (91% vs. 99% vs. 96%, P=.02), more likely to be MRD+ (64% vs. 34% vs. 36%, P=.03), had a higher relapse rate (5-year: 39% vs. 24% vs. 38%, P=.01) and lower OS (5-year: 41% vs. 64% vs. 49%, P=.02), see Table. Patients who achieved MRD negativity had better OS (MRD+ vs MRD-, P=.01). Importantly, no statistically significant difference in OS, relapse or non-relapse mortality were noted between the 3 groups in patients who underwent allo-HCT in CR1. Conclusions: Ph-like ALL is a high risk subgroup with increased prevalence in younger adults. Allo-HCT appears to offset the poor prognosis associated with this entity. A targeted FISH panel offers timely recognition of this entity in a clinical setting.[Table: see text]

Abstract Introduction: Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand that can restore integrity to damaged intestinal mucosa in murine models of acute graft-versus-host disease (aGVHD). We previously described AREG as a circulating biomarker of late-onset aGVHD, but its relevance combined with clinical risk factors has not yet been tested in a large cohort of patients with aGVHD occurring prior to day 100 post-transplant. We therefore tested samples from two aGVHD first-line treatment trials, Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0302 and 0802, and identified a clinically relevant threshold level of circulating AREG at aGVHD onset. We then investigated whether incorporating AREG into the refined Minnesota Risk Score could further risk-stratify patients. Patients and Methods: Blood samples were obtained at the onset of systemic aGVHD treatment within BMT CTN 0302 (serum) and BMT CTN 0802 (plasma). All patients with response data and samples for analysis from both trials were included (N=251). We determined the association of AREG with clinical outcomes, including risk stratification by the refined Minnesota criteria, day 28 complete/partial response (CR/PR) to first-line therapy, 2-year overall survival (OS) and 6-month and 2-year non-relapse mortality (NRM). We investigated the effect of AREG on clinical endpoints per a doubling in the value of AREG, defined a clinically relevant threshold level in the AREG values using two-fold cross-validation, and confirmed the clinical relevance of this cut-point in independent samples (N=92) from pooled from drawn from the Chronic GVHD Consortium and the Mount Sinai Acute GVHD International Consortium (MAGIC). Results: In patients enrolled in BMT CTN 0302/0802, AREG levels were 1.7-fold higher in patients with Minnesota high-risk (HR) compared to standard-risk (SR) aGVHD (HR median 53.4 vs SR 31 pg/ml, p&lt;0.01). Every 2-fold increase in AREG was associated with a 33% decrease in the likelihood of day 28 CR/PR (odds ratio [OR] 0.67, p&lt;0.01, table). Clinical factors alone, as determined by the refined Minnesota Risk Score, were associated with day 28 CR/PR (p=0.02, table). Adding AREG to the Minnesota Risk Score could further risk-stratify patients. Minnesota SR patients with elevated AREG ≥ 33 pg/mL showed a 59% lower odds of day 28 CR/PR than SR patients with low AREG (OR 0.41, p=0.02). Patients with Minnesota HR aGVHD with AREG ≥ 33 pg/mL had the worst outcomes, with an 82% lower odds of day 28 CR/PR in comparison to HR with low AREG (OR 0.18, p&lt;0.01). High AREG was associated with worse OS and NRM in both Minnesota SR (hazard ratios 2-year OS 2.3, p&lt;0.01 and 6 month NRM 2.95, p=0.01, respectively) and HR patients (hazard ratios 2-year OS 3.35, p&lt;0.01 and 6-month NRM 9.38, p&lt;0.01 respectively, figure). Finally, in independent samples from the Chronic GVHD Consortium/MAGIC we confirmed that high AREG was associated with worse day 28 CR/PR (55.2% vs. 79.4%, p=0.02) and significantly worse 6-month survival after the onset of aGVHD (57.1% vs. 82.5%, p=0.01). Conclusion: AREG is elevated in patients with poor aGVHD outcomes and adds to the accuracy of risk stratification when combined with the refined Minnesota Risk Score. AREG ≥33 pg/mL at aGVHD onset is associated with lower day 28 CR/PR and higher mortality in samples from 4 multicenter cohorts. The mechanism of elevated circulating AREG in severe aGVHD is not yet known, although we hypothesize the degree of AREG elevation reflects the intensity of immune-mediated tissue injury resulting in AREG release. With accumulating evidence of altered EGFR ligands in aGVHD, further investigation into epithelial repair pathways involving AREG may lead to new adjunctive therapies to overcome poor steroid response in high-risk aGVHD. Disclosures Holtan: Incyte: Other: One-time advisory board member. Khera: Novartis: Consultancy. Lee: Mallinckrodt: Honoraria; Amgen: Other: One-time advisory board member; Bristol-Myers-Squibb: Other: One-time advisory board member; Kadmon: Other: One-time advisory board member. Chen: Immudex: Research Funding. Arora: Takeda Oncology: Consultancy. Flowers: Pharmacyclics: Consultancy. Cutler: Pfizer: Consultancy; Kite: Consultancy; Incyte: Consultancy; Bristol-Myers Squibb: Consultancy; Pharmacyclics: Consultancy; Astellas: Consultancy. Jagasia: Janssen: Consultancy, Research Funding; Therakos: Consultancy, Research Funding; Mallinckrodt: Consultancy. Hexner: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Levine: Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. MacMillan: Magenta Therapeutics: Research Funding.

Introduction Orally administered tacrolimus is widely used in hematopoietic cell transplant patients, but multiple clinical situations may arise rendering oral administration infeasible. The undesirable sequelae of intravenous administration, including toxicity, challenges with administration and cost call for innovative solutions to conserve existing supply and optimize safety and efficacy of medication delivery. We sought to demonstrate feasibility of sublingual tacrolimus use and estimate a sublingual-to-oral (SL:PO) conversion ratio in the hematopoietic cell transplant setting. Methods Ten adults undergoing allogeneic hematopoietic cell transplant received tacrolimus 0.04 mg/kg/dose twice daily. Initial doses were given via sublingual route and a steady state trough level was collected after 4 consecutive doses. Participants were then switched to oral tacrolimus, the dose adjusted for a goal trough 8-12ng/mL, and another steady state trough was drawn. Total daily dose was divided by trough concentration for each route to determine the dosing ratio of SL:PO. Results Median trough level following sublingual administration was 11.3 ng/mL. Three of these were within goal, 3 were low (4.7–6.4 ng/mL) and 4 were elevated (15.9–18.6 ng/mL). Median SL:PO ratio was 1.02. In 5 participants the SL:PO ratio was <1 (range 0.57–0.94) and in 5 the ratio was ≥1 (range 1.10–1.92). No significant barriers or intolerance to sublingual tacrolimus use were noted. Conclusions Results demonstrate reliable absorption with sublingual tacrolimus use in patients undergoing hematopoietic cell transplant. Sublingual administration may allow for avoidance of the undesirable complications of IV tacrolimus, such as increased toxicities, required hospitalization for continuous infusion, risk of dose conversion and dilution errors and increased cost. Trial Registry name: Use of Sublingual Tacrolimus in Adult Blood and Marrow Transplant Patients, NCT04041219 https://clinicaltrials.gov/ct2/show/NCT04041219?term=NCT04041219&draw=2&rank=1

AbstractBackgroundNeutropenia is a risk factor for development of infections; however, the direct effect of neutropenia on development of bloodstream infection (BSI) is not known. D‐index, which is area between the neutrophil time curve and a neutrophil count of 0.5 × 109/L, incorporates the combined effect of severity and duration of neutropenia. We aimed to evaluate whether D‐index can be used as a marker for BSI in patients with allogeneic stem cell transplantation.MethodWe conducted a retrospective cohort study of patients undergoing allogeneic stem cell transplantation between January 1, 2005, and September 30, 2015. The primary outcome measure was the development of BSI within 30 days of transplantation.ResultsA total of 714 patients were included in the study of whom 101 developed BSI. Patients with BSI had a significantly higher median D‐index value compared with patients who did not have BSI (4990 vs. 3570, P < .001). As a marker, the performance of the D‐index was similar to that of the duration of profound neutropenia (P = .18) and significantly better than the total duration of neutropenia (P = .001).ConclusionThe D‐index performed better than the total duration of neutropenia as a marker for BSI in patients with allogeneic stem cell transplantation. There was no difference between D‐index and, a more easily calculable indicator, duration of profound neutropenia.