Number Of High-risk Patients Research Articles

New insights into hematopoietic cell transplantation in ALL: Who should be transplanted, when, and how

Advancements in multi-agent chemotherapy through clinical trials conducted by multi-institutional collaborative groups worldwide, along with risk stratification using molecular genetic features and treatment responses, including minimal residual disease, have significantly improved outcomes for children and adolescents with acute lymphoblastic leukemia (ALL) over the past half-century. However, for a certain number of high-risk patients, including those with relapsed or refractory disease, for whom existing chemotherapy alone is insufficient for cure, allogeneic hematopoietic cell transplantation (HCT) has provided a potential opportunity for leukemia cure. For these patients, the appropriate selection of donor and stem cell source, conditioning regimen, timing of transplantation, and comprehensive supportive care, including effective graft-versus-host disease prophylaxis, are prerequisites for successful HCT. While HCT from a human leukocyte antigen (HLA)-matched sibling has traditionally been the preferred option, less than 25 % of patients currently have such a donor in developed countries. Consequently, alternative donor HCT options, such as those from matched unrelated donors identified through high-resolution HLA typing, unrelated cord blood donors, and more recently, haploidentical donors using post-transplant cyclophosphamide or TCRαβ+/CD19+ cell-depleted grafts, are providing broader access to HCT for patients lacking matched sibling donors. Nonetheless, HCT carries the risk of various acute and late toxicities. In particular, the use of myeloablative conditioning with total body irradiation, a standard in pediatric ALL, is associated with significant long-term sequelae. As our understanding of the pathophysiology of the disease improves and novel molecular targeted therapies and immunotherapies are developed, the indication for HCT in pediatric ALL is becoming more selective, leading to a gradual decrease in the number of transplants performed. However, further optimization and evolution of allogeneic HCT are needed to both maximize its anti-leukemia effects and minimize transplant-related complications, as there remain cases that undoubtedly require HCT for the cure of leukemia.

Development of a Discharge Counseling and Medication Reconciliation Process for Pediatric Patients Within a Large, Academic Health System

OBJECTIVE This study aims to characterize the impact of a pharmacist-driven discharge medication reconciliation and counseling program targeting high-risk pediatric patients to mitigate barriers in transitions of care. METHODS This was a single-center quality improvement initiative including high-risk pediatric patients within a large academic medical center. Pharmacy, medical, and information technology team members developed a scoring system to identify patients at high risk of hospital readmission that resulted in a trigger tool built within the electronic medical record (EMR). Pharmacy workflow, the EMR documentation, and staff training were implemented. The primary end point was the number of high-risk patients with complete medication reconciliation and/or discharge counseling performed during the first 2 months after implementation. The secondary end points included quantification and qualification of the interventions conducted by a pharmacist. RESULTS Pediatric clinical pharmacists conducted discharge medication reconciliation and/or counseling for 60 patients during the first 2 months after implementation. There were 65 interventions performed, including 60 discharge medication reconciliations and 5 discharge counseling sessions. Of these interventions, 22 were recommendations on appropriate medication dosing and frequency (37%), 12 on duration of therapy (20%), and 8 were medication additions (13%). There were 6 interventions on adherence assistance (10%), 6 involved selection of medication formulation (10%), 3 involved medication discontinuation (5%), 2 involved appropriate therapy selection (3%), and 1 involved medication stability (1%). All interventions were accepted and implemented by the prescribing providers. CONCLUSIONS Pharmacist-driven discharge medication reconciliation and counseling programs targeting pediatric high-risk population might be an effective tool to mitigate gaps in transitions of care.

Combined Band and Plate Fixation as a New Individual Option for Patients at Risk of Sternal Complications after Cardiac Surgery: A Single-Center Experience.

Due to the advent of interventional therapies for low- and intermediate-risk patients, case complexity has increased in cardiac surgery over the last decades. Despite the surgical progress achieved to keep up with the increase in the number of high-risk patients, the prevention of sternal complications remains a challenge requiring new, individualized sternal closure techniques. The aim of this study was to evaluate the safety and feasibility, as well as the in-hospital and long-term outcomes, of enhanced sternal closure with combined band and plate fixation using the new SternaLock® 360 (SL360) system as an alternative to sternal wiring. From 2020 to 2022, 17 patients underwent enhanced sternal closure using the SL360 at our institution. We analyzed perioperative data, as well as clinical and radiologic follow-up data. The results were as follows: In total, 82% of the patients were treated with the SL360 based on perioperative risk factors, while in 18% of cases, the SL360 was used for secondary closure due to sternal instability. No perioperative complications were observed. We obtained the follow-up data of 82% of the patients (median follow-up time: 141 (47.8 to 511.5) days), showing no surgical revision, no sternal instability, no deep wound infections, and no sternal pain at the follow-up. In one case, a superficial wound infection was treated with antibiotics. In conclusion, enhanced sternal closure with the SL360 is easy to perform, effective, and safe. This system might be considered for both primary and secondary sternal closure in patients at risk of sternal complications.

Utilizing a Questionnaire to Implement a Risk-based Antibiotic Prophylaxis Protocol for Transrectal Prostate Biopsy

To develop and evaluate a risk-based antibiotic prophylaxis protocol for patients undergoing transrectal prostate biopsy. We created a risk-based protocol for antibiotic prophylaxis before transrectal prostate biopsy. Patients were screened for infection risk-factors with a self-administered questionnaire. The protocol was implemented from January 1, 2020 to March 31, 2020. We compared patient risk-factors, antibiotic regimens, and 30-day infection rates for patients undergoing transrectal prostate biopsies during the intervention and for a 3-month period before the intervention. There were 116 prostate biopsies in the preintervention group and 104 in the intervention group. Although there was no significant difference in the number of high-risk patients between the 2 groups (48% vs 55%; P = .33), the percentage of patients treated with augmented prophylaxis decreased from 74% to 45% (P = 0.03). The duration of antibiotic administration and the median number of doses prescribed also decreased significantly. Despite significant decreases in antibiotic use, there were no differences in infection rates (5% vs 5%; P = .90) or sepsis rates (1% vs 2%; P = .60). We developed a risk-based protocol for prophylactic antibiotics before prostate biopsy. The protocol was associated with less antibiotic use but did not lead to an increase in infectious complications.

Abstract P4-07-17: Follow-up in breast cancer care: guidelines and individual risks

Abstract The aim of this study was to investigate how breast cancer follow-up in the Netherlands changed during the COVID-19 pandemic, compared to 2018-2019, and to what extent follow-up during the pandemic corresponded to the patient risk of recurrence. During the early phase of the pandemic the Dutch Society for Surgical Oncology (NVCO) issued a report with recommendations on how follow-up could be postponed, as a guidance for the pandemic, based on a low, intermediate or high risk of recurrence. In this study we investigated to what extent this advice was followed. A dataset of 33160 women diagnosed with primary invasive breast cancer between January of 2017 and July of 2021 was selected from the Netherlands Cancer Registry (NCR) and Dutch Hospital Data (DHD). The pandemic, 2020 and weeks 1-32 of 2021, was divided into six periods (A to F), based on the number of hospitalized COVID patients in the Netherlands. The five-year risk of locoregional recurrence (LRR) was determined for each patient with the INFLUENCE nomogram. The LRR risk was compared to the risk groups from the NVCO report with a Kruskal-Wallis test. The percentage of patients who received a mammogram during period A to F was compared to the same periods of 2018-2019 with a chi-squared test. Correlation between the LRR risk, and if patients had a mammogram, was investigated with logistic regression. This analysis was repeated separately for the risk groups. Correlation between the LRR risk, and time intervals between surgery and the first and second mammogram was analyzed using cox proportional hazard models, this was also repeated for the risk groups. There was a significant difference in LRR risk between the NVCO risk groups. In the low-risk group (n=7673), 86 patients (1.1%) had a risk >5%. In the intermediate risk group (n=19197), 18364 patients (95.7%) had a risk of < 5%, and 65 patients (0.34%) had a risk of >10%. In the high-risk group (n=2674), 2365 patients (88.4%) had a risk < 10%. The percentage of patients who received a mammogram was significantly lower in periods B to F of the pandemic. Logistic regression showed a negative correlation between the risk of LRR and if patients had a mammogram in 2020 (OR 0.93) and 2021 (OR 0.93). There was also a negative correlation between the risk groups and mammography in 2020 (OR 0.92 for intermediate and 0.80 for high), and for the risk groups and mammography in 2021 (OR 0.98 for intermediate and 0.95 for high). There was no significant impact of LRR risk, or risk group, on time intervals between mammograms. During the pandemic, patients with a higher LRR risk, or a higher risk according to NVCO advice, had lower odds of having a mammogram. If the advice would have been followed, in 0.5% of the patients scheduled for follow-up, the recommendation was to postpone in contrast to a high estimation of the individual risk. For 62.7%, a follow-up was recommended, despite a low estimated individuals risk. Because the number of high-risk patients is relatively low, individual risk prediction could be supportive, in case of future restrictions. This way the high-risk patients can be identified and prioritized for follow-up, and can also be encouraged to come to the hospital. Citation Format: Lotte Van Dongen, Joyce Meijer, Jolanda Van Hoeve, Desiree van den Bongard, Marielle Hendriks, Aafke Honkoop, Luc Strobbe, Cristina Guerrero Paez, Sabine Siesling. Follow-up in breast cancer care: guidelines and individual risks [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-17.

Artificial intelligence-assisted evaluation of tumor infiltrating CD3+ and CD8+ T cells for prognostication and prediction of benefit from adjuvant chemotherapy in early stage colorectal cancer (CRC): A retrospective analysis of the QUASAR trial.

204 Background: High CD3+ (all) and CD8+ (cytotoxic) T cell densities in the core (CT) and invasive margin (IM) of primary CRCs have been shown to be associated with superior prognosis at all stages of disease. Their predictive effect on benefit from adjuvant chemotherapy in early stage CRC has not been tested. Methods: FFPE samples from participants (pts) in the QUASAR trial (adjuvant fluorouracil/folinic acid vs observation in stage 2/3 CRC) were analysed for CD3 and CD8 immunohistochemistry (IHC). Pathologists annotated the core and peritumor areas on digital slide images. Artificial intelligence (AI) algorithms delineated the CT and IM, and calculated the densities (cells/mm2) of each marker in each region (CD3-CT, CD3-IM, CD8-CT, CD8-IM). Pts were randomly partitioned into test and validation sets (1:1). In the test set, each measure’s prognostic effect on recurrence-free interval (RFI) (primary endpoint), colorectal cancer mortality (CCM) and overall survival (OS) in each trial arm was assessed. Maximum likelihoods methods were used to develop optimal cut-points. Analyses were repeated in the validation set. Analysis of 425 pts in each set would give > 95% power (α = 0.05, 2-sided) to detect a twofold difference in recurrence risk. In predictive analyses, 2-year recurrence rate was the primary outcome; biomarker-treatment interactions were assessed. Results: Tumor tissue from 868 pts (797 [92%] stage 2; 531 [61%] colon) was analysed, with evaluable results for CD3-CT in 851 (98.0%), CD3-IM in 833 (96.0%), CD8-CT in 849 (97.0%) and CD8-IM in 820 (94.5%) pts. In the test set, optimal cut-points of 318, 798, 81 and 186 cells/mm2 were defined for CD3-CT, CD3-IM, CD8-CT and CD8-IM respectively. The recurrence rate in the high-risk group was twice that in the low-risk group for all measures (CD3-CT: rate ratio [RR] 2.00, [95%CI 1.33-2.94], p = 0.0008; CD3-IM: 2.38, [1.59-3.57], p < 0.00001; CD8-CT: 2.17, [1.59-3.57], p = 0.0001; CD8-IM: 2.13 [1.43-3.23], p = 0.0001), which was closely replicated in the validation set (CD3-CT: RR 1.96, [1.30-2.94], p = 0.002; CD3-IM: 1.79, [1.18-2.70], p = 0.005; CD8-CT: 1.72, [1.18-2.56], p = 0.005; CD8-IM: 1.72 [1.15-2.56], p = 0.008). In multivariate analyses, prognostic effects were similar in colon and rectal cancers, and in stage 2 and 3 disease. CD3/8 counts were not predictive of benefit from adjuvant chemotherapy, with similar efficacy in the high and low risk groups. Conclusions: AI-assisted CD3 and CD8 counts were strongly associated with tumor recurrence rates. With no biomarker-treatment interactions, proportional reductions in recurrence with chemotherapy were similar in high and low-risk disease. Hence, numbers of high-risk patients needed to treat to prevent one recurrence were about half the number for low-risk patients.

Incidence and Mortality of Second Primary Malignancies after Lymphoma

Introduction: Treatment for lymphoma has undergone significant transformation in the past decade with the introduction of novel treatment strategies. Given the long-term treatment and supportive care, patients with lymphoma are living longer under better disease control, and patients with lymphoma are at increased risk of developing second primary malignancies (SPMs). Herein, we estimated the incidence, risk factors, and outcomes in lymphoma survivors with SPMs. Methods: Patients diagnosed with SPMs after primary lymphoma in Shandong Provincial Hospital (SPH) from 2010 to 2021 were included. Additionally, the differences in the incidence and characteristics of SPMs across ethnic groups were delineated by comparing with the Surveillance, Epidemiology, and End Results (SEER) database. We calculated the risk of SPMs using standardized incidence ratio (SIR) and absolute excess risk (AER). Overall survival (OS) analysis was reported using the Kaplan-Meier method. Results: A total of 2,912 hospitalized lymphoma cases were included, and 63 patients (2.16%) had SPM during the follow-up. Of these patients, 44 (69.84%) were male and 19 (30.16%) were female. The median age was 61 years old (range 35-81) and the majority of patients diagnosed with SPMs were older (≥60 years old, 61.90%) and previously treated with chemotherapy (69.84%). Histopathologic subtypes of primary lymphoma were as follows: (1) Hodgkin's lymphoma (HL, 3.17%), (2) non-Hodgkin lymphoma (NHL, 80.96%), and (3) Unknown type (15.87%). Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and diffuse large B-cell lymphoma (DLBCL) were the most common subtypes. The median duration between SPMs and lymphoma was 3.14 years (range 0-9). The most common types of SPMs were digestive system tumors (27, 42.86%), respiratory system tumors (13, 20.63%), and urinary system tumors (8, 12.70%). Specifically, the common types of SPMs were lung (19.6%), stomach (10.7%), and liver (8.9%) (Fig. 1). In addition, 304,696 new lymphoma cases are diagnosed, as reported to SEER 18 registries from 2010 through 2018, and 13580 survivors (4.46%) had SPMs. As described above, these patients with SPMs were also mostly male and older when diagnosed with SPMs. The commonly diagnosed SPMs are NHL (17.7%), lung and bronchus cancer (12.1%), and prostate cancer (10.0%). Additionally, we showed that the incidence rate of SPMs after specific lymphoma in the SEER database was higher than that of the SPH database other than CLL (Fig. 2). Because the crude incidence rate of SPM was not adjusted for the expected number of lymphoma or the number of high-risk patients in a reference population, the SIR and AER of SPM were calculated in the further analysis. Among patients at lymphoma diagnosis, overall malignancy risk was significantly higher than expected in the U.S. general population after follicular lymphoma (FL, SIR=2.01; 95%CI 1.93-2.09), marginal zone lymphoma (MZL, SIR=1.78; 95%CI 1.68-1.88), HL (SIR=1.76; 95%CI 1.62-1.91), CLL/SLL (SIR=1.51; 95%CI 1.46-1.57) and DLBCL (SIR=1.45; 95%CI 1.39-1.5). Moreover, hematological malignancies (SIR=3.23; 95%CI 3-3.48) contributed more to the SPMs than solid-organ cancers (SIR=1.31; 95%CI 1.226-1.27) among these subtypes. In a multivariate analysis, most patients with SPMs were diagnosed at younger ages (<55 years) and found to be other (Asian or Pacific Islander, American Indian/Alaska Native) races. Additionally, a higher mortality rate is associated with advanced age, no rituximab-based chemotherapy, and latency (P<0.05). We found that OS is shorter for patients with SPMs compared with those without SPMs, with increasing divergence over time (P<0.00001). In further analysis, we compared the survival of the most common SPMs in people who were diagnosed with specific lymphoma. The results showed that lymphoma patients with NHL, urinary bladder, stomach, and lung cancer experienced worse survival compared with melanoma, thyroid, kidney, and breast cancer (P<0.00001). Conclusion: Our study illustrated the incidence, mortality, and related risk factors of SPMs in specific lymphoma survivors and showed that the incidence of SPMs after the lymphoma is higher in older men, particularly in lung cancer. We found an increased risk for lymphoma compared to the general population. More studies are needed to understand the molecular underpinning leading to increased SPM formation in lymphoma patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A 3-step approach to predict advanced fibrosis in nonalcoholic fatty liver disease: impact on diagnosis, patient burden, and medical costs

A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs.

Childhood acute lymphoblastic leukemia: Four years evaluation of protocols 2013 and 2016 in a single center in Indonesia, a lower-middle-income country.

The prognosis of childhood acute lymphoblastic leukemia (ALL) in Indonesia, a lower-middle-income country (LMIC), is lower than in high income countries (HICs). The Indonesian ALL2013 protocol resulted in too many toxic deaths (21%) and abandonments (11%). Therefore, we drafted an adapted protocol, ALL2016. Main changes: no anthracyclines in standard risk (SR), prednisone replaced dexamethasone at induction in high risk (HR), and anthracyclines and cyclophosphamide were rescheduled in HR. Patients (aged: 1-18 years) were stratified into SR and HR. HR was defined as age over 10 years, leucocyte count over 50×109 /L, central nervous system (CNS) involvement, mediastinal mass, T-cell phenotype, testicular involvement, or poor prednisone response. ALL2013 included 174 patients (106 SR and 68 HR) and ALL2016 188 (91 SR and 97 HR). Although the number of HR patients was significantly higher in ALL2016 (51.6%vs. 39.1%; p=.017), the outcome of ALL2016 improved over ALL2013 (4-year-probable overall survival (pOS) 60.1%vs. 50.0%; p=.042 and 4-year-probable event-free survival (pEFS) 49.5%vs. 36.8%; p=.018). ALL2016 showed a nonsignificant advantage for SR patients (4-year-pEFS 56.0%vs. 47.2%; p=.220 and 4-year-pOS 70.3%vs. 61.3%; p=.166), but less toxic deaths (7%vs. 20%; p=.011). In HR group, the outcomes were significantly better in ALL2016 (4-year-pEFS 43.3%vs. 20.6%; p=.004; 4-year-pOS 50.5%vs. 32.4%; p=.014) especially due to less relapses (31%vs. 62%; p=.001). Isolated CNS relapses went down from 18 to 8% in HR (p=.010) and 11 to 5% in SR (p=.474). Both SR and HR showed lower numbers of abandonment in ALL2016 (6%vs. 14%; p=.039). Overall ALL2016 results improved over ALL2013. Modest changes in protocol resulted in less initial toxicity and abandonments.

Mental status of healthcare professionals according to the level of exposure to COVID-19 patient during the pandemic

Introduction: The frontline healthcare workers during the coronavirus outbreak work under intense pressure while working in close contact with COVID-19 patients, and can subsequently develop mental health-related problems. This study aimed to evaluate the mental impact of COVID-19 on healthcare workers according to exposure level. Material and Method: This cross-sectional study included a total of 282 participants. Healthcare workers were divided into two groups as low-risk contact and high-risk contact according to the degree of contact with the coronavirus. Anxiety, depression, and insomnia were evaluated among the groups using the Insomnia Severity Index (ISI), General Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scales. Results: One hundred seventy eight (62.4%) women and 104 (36.8%) men, with a mean age of 24.59 years were included in this study. The number of low-risk patients was 180 (63.8%), while the number of high-risk patients was 102 (36.1%). In addition, according to the multivariate analysis, staff working in the department with high-risk contact had significantly lower high to suffer anxiety (OR 1.283, 95% CI 1.109-1.483, p=0.001), depression (OR 1.052, 95% CI 1.019-1.088, p=0.001) and insomnia (OR 3.460, 95% CI 2.506-4.784, p

The potential of new prediction models for emergency medical dispatch prioritisation of patients with chest pain: a cohort study

ObjectivesTo develop emergency medical dispatch (EMD) centre prediction models with high sensitivity and satisfying specificity to identify high-priority patients and patients suitable for non-emergency care respectively, when assessing patients with chest pain.MethodsObservational cohort study of 2917 unselected patients with chest pain who contacted an EMD centre in Sweden due to chest pain during 2018. Multivariate logistic regression was applied to develop models predicting low-risk or high-risk condition, that is, occurrence of time-sensitive diagnosis on hospital discharge.ResultsPrediction models were developed for the identification of patients suitable for high- and low-priority dispatch, using 11 and 10 variables respectively. The area under the receiver-operating characteristic curve (AUROC) for the high-risk prediction model was 0.79 and for the low-risk model it was 0.74. When applying the high-risk prediction model, 56% of the EMS missions were given highest priority, compared with 65% with the current standard. When applying the low-risk model, 7% were given the lowest priority compared to 1% for the current standard. The new prediction models outperformed today’s dispatch priority accuracy in terms of sensitivity as well as positive and negative predictive value in both high- and low-risk prediction. The low-risk model predicted almost six times as many patients as having low-risk conditions compared with today’s standard. This was done without increasing the number of high-risk patients wrongly assessed as low-risk.ConclusionsBy introducing prediction models, based on logistic regression analyses, using variables obtained by standard EMD-questions on age, sex, medical history and symptomology, EMD prioritisation can be improved compared with using current criteria index-based ones. This will allow a more efficient emergency medical services resource allocation.

Reducing Heart Failure Hospitalizations Through Enhancement Of Multidisciplinary Roles And Targeted Patient Oversight

Reducing Heart Failure Hospitalizations Through Enhancement Of Multidisciplinary Roles And Targeted Patient Oversight

Value of duplex ultrasound of carotid and lower extremity arteries in the restratification of cardiovascular risk and initiation of lipid-lowering therapy

Aim. To study the role of duplex ultrasound (DU) of carotid and lower extremity arteries in the restratification of cardiovascular risk (CVR) and changing the indications for lipid-lowering therapy.Material and methods. The study included 291 patients aged 40-64 years without established atherosclerotic cardiovascular diseases. All patients underwent DU of carotid and.Results. Carotid DU make it possible to restratify 140 (65,7%) patients with low/moderate CVR (out of 213) into the category of high/very high CVR. Lower extremity artery DU resulted in the restratification of 101 (47,4%) patients with low/moderate CVR (out of 213) into the category of high/very high CVR. The use of a multifocal ultrasound technique demonstrated the highest restratification power and allowed 161 (75,6%) patients (out of 213) to be assigned to the high/very high CVR group. The use of peripheral arterial DU led to an increase in the number of high-risk patients by 2,33-3,02 times. The proportion of persons with indications for lipid-lowering therapy increased from 50 (21,0%) patients to 170 (71,4%).Conclusion. In patients aged 40-64 years without established atherosclerotic cardiovascular diseases, the use of DU of carotid and lower extremity arteries made it possible to classify 75,6% of patients with low/moderate CVR in the group of patients with high and very high CVR. According to CVR reclassification, the proportion of patients with indications for lipid-lowering therapy increased from 21,0 to 71,4% of patients.

Acute Myeloid Leukemia Patients in Complete Remission with Positive Measurable Residual Disease Prior to Allogeneic Transplant Have Worse Outcomes, Similar to Active Disease Regardless of Conditioning Regimen Intensity and Post-Transplant Cyclophosphamide Administration

IntroductionAllogenic hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML) is a curative option in patients with intermediate/high risk disease who achieve morphologic complete remission (CR) after induction chemotherapy. Patients in CR but with positive measurable residual disease (pMRD) prior to HCT had high relapse risk(RR) (67% vs 65%) and low 3 year overall survival (OS) (26% vs 23%),similar to those with active disease in a single institution study (Araki et.al; Volume 34, Feb 1,2016, JCO). However, this study included only patients who received myeloablative conditioning (MAC) and included both peripheral blood and marrow grafts. A single institution retrospective study showed that use of MAC compared to reduced intensity conditioning (RIC) improved 3 year RR(19% v 67%; P < .001) and OS( 61% v 43%; P = .02) in patients with pMRD/CR(determined by molecular analysis of limited gene mutational panel)(Hourigan et.al. Volume 38, April 20,2020, JCO). We analyzed a cohort of AML patients that underwent either MAC or RIC followed by peripheral blood stem cell grafts and post-transplant cyclophosphamide (PTCy) based GVHD prevention regimen at our institution to determine the effect of pMRD on transplant outcomes.Methods:To evaluate the impact of pMRD on transplant outcomes, we analyzed AML patients who underwent HCT at Levine Cancer Institute between June 2014 and April 2020 with MRD testing performed within 1 month prior to HCT. MRD testing was performed at University of Washington by using multiparametric flow cytometry (MPC). The overall sensitivity of the assay is conservatively estimated as 0.1%. In our institution, all patients received MAC (Bu/Flu) or RIC (Bu/Flu or Flu/Cy/TBI) regimens followed by peripheral blood stem cell grafts and identical PTCy-based GVHD prophylaxis regimens that included tacrolimus and mycophenolate. Patient and transplant related characteristics were presented via descriptive statistics. Corresponding P-values were determined using Fisher's exact test for categorical variables and nonparametric Mann-Whitney U test for continuous variables. Relapse-free survival (RFS) and OS were estimated using the Kaplan Meier method. All statistical tests were two sided, and a P-value < 0.05 was considered statistically significant.ResultsFrom June 2014 to April 2020, 105 patients with AML underwent HCT. Eighty-three patients with MRD results were included in the final analysis - 52 (63%) with negative MRD (nMRD)/CR, 16 (19%) with pMRD/ CR and 15 (18%) with active disease (no CR). Baseline characteristics were similar except for presence of significantly greater number of high risk patients, based on ASTCT disease classification in the active disease group compared to pMRD/CR and nMRD/CR cohorts( 87% vs 19% vs 0%, P =< 0.001). Median follow up for the entire cohort was 32.7 months. RFS was superior in patients with nMRD/ CR compared to pMRD/ CR or active disease (56.4% vs 19.4% vs 35%, P= 0.005). In addition, OS was superior in nMRD/ CR compared to pMRD/CR or active disease (56.7% vs 35.2% vs 40%, P= 0.014). The use of MAC compared to RIC did not improve RFS (0% vs 32%, P= 0.018) and OS (0% vs 44%, P= 0.071) in pMRD/CR cohort. The use of MAC or RIC did not significantly impact RFS (69% vs 52%, P=0.729) or OS (61% vs 53%, P=0.739) in nMRD/CR patients.Conclusion:Our study validates the previous data that prognosis of patients with pMRD/CR (determined by MPC) prior to HCT is not significantly better than those having active disease. The outcomes were poor regardless of conditioning regimen intensity and PTCy based GVHD prophylaxis used at our institution. These patients might benefit from additional chemotherapy or targeted treatments to achieve nMRD prior to HCT and/or maintenance therapy post HCT. Patients with nMRD/CR disease had similar outcomes with MAC or RIC. This finding suggests that less aggressive conditioning regimens incorporating PTCy could be considered in a subset of patients with nMRD/CR, thereby sparing them from complications associated with MAC. Prospective trials are needed to further study these findings. [Display omitted] DisclosuresCopelan: Amgen: Consultancy. Grunwald: Astellas: Consultancy; Karius: Consultancy; PER: Other; Gilead: Consultancy; Incyte: Consultancy, Research Funding; Amgen: Consultancy; PRIME: Other; Daiichi Sankyo: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Trovagene: Consultancy; Stemline: Consultancy; Pfizer: Consultancy; Janssen: Research Funding; Blueprint Medicines: Consultancy; Sierra Oncology: Consultancy; Med Learning Group: Other; Cardinal Health: Consultancy; MDEdge: Other; Agios: Consultancy.

Long-term Outcome of Children with Acute Lymphoblastic Leukemia Treated with IC-BFM2002 Regimen

Background: Changes in pediatric chemotherapy regimens over the last three decades have introduced a variety of protocols to increase the survival of patients with acute lymphoblastic leukemia (ALL). Intercontinental Berlin-Frankfort-Munich (IC-BFM) 2002 is one of the protocols widely used in countries that could not perform minimal residual disease by polymerase chain reaction (MRD PCR) method. Evaluation the results of these regimens is very effective in improving their quality.&#x0D; Materials and Methods: Children with newly diagnosed ALL in Ali Asghar Children's Hospital were randomly divided into two groups. Patients in both groups underwent chemotherapy according to IC-BFM 2002 protocol. Patients were divided into two groups based on the type of reinduction regimen, so that patients in-group A received protocol II and patients in-group B received protocol III as a reinduction regimen. Then demographic information and patient outcome were statistically analyzed with SPSS 23.&#x0D; Results: Sixty-three patients were included in the study. There were 32 patients in-group A (18 boys and 14 girls) and 31 patients in-group B (11 boys and 20 girls). The number of high-risk patients was higher in-group A, but this difference was not statistically significant. The recurrence rate in-group B patients was about seven times higher than the recurrence rate in group A patients, and this difference was statistically significant. In-group A, no patients had an early relapse, while about half of the recurrences in-group B occurred as early relapse and the rest as late relapse. CNS recurrence occurred in only two patients. 5-yr EFS of all enrolled patients was 88.90 ± 8.00% (95% CI). This rate for group A and B was 96.90 ± 6.20% (95% CI) and 80.60 ± 14.20% (95% CI), respectively (P=0.022).&#x0D; Conclusion: It seems that IC-BFM 2002 protocol is an appropriate treatment regimen with acceptable results for children with ALL in developing countries, a workable protocol with significant consequences. Protocol II seems to be suitable for reinduction and increasing the Methotrexate dose may not be necessary for non-high-risk groups.

Kidney Transplant From Elderly Donors: A Center Experience

BackgroundRenal transplantation is the treatment of choice in end-stage renal disease. With the aging of the population and better medical care available, the number of high-risk patients in terms of age and comorbidities on transplant waiting lists is increasing. Due to severe organ shortage, the use of expanded criteria and elderly donors is also increasing. We will review the outcomes of graft function and survival from a series of transplants from elderly deceased donors and compare the characteristics of the organs from donors older and younger than 70 years. MethodsWe collected data from our transplant unit from 1993 until May 2019 and considered 2 groups of donors: donors A (aged ≥70 years) and donors B (aged <70 years). ResultsThe donors A group had more comorbidities with consequently higher Kidney Donor Profile Index scores than the donors B group, although there was no statistical difference regarding pre-donation serum creatinine level. Among transplant recipients, we also considered 2 groups, according to the age of the organ received: recipients A and recipients B. No difference was found between groups regarding the number of HLA mismatches, incidence of delayed graft function, number of hospitalizations, or incidence of acute rejection. Recipients’ age, cold ischemia time, and graft function 1 year after transplant were worse in the recipients A group. ConclusionsAlthough kidney graft function was worse in recipients from elderly donors, this difference had no clinical relevance, showing a possible benefit in patient survival compared with permanence in dialysis, so this type of transplant could be considered for older recipients.

Implementation of Targeted Point of Care HIV Testing in a Pediatric Emergency Department.

Introduction:HIV infection rates are increasing among adolescents. Despite guidelines recommending annual HIV screening among sexually active adolescents, 3.6% of adolescents tested for other sexually transmitted infections (STI) in a pediatric emergency department (PED) were screened for HIV. The aim was to increase HIV screening to 90%.Methods:Interventions were designed to address 4 key drivers thought to be critical in reliably offering HIV testing. The primary outcome measure was the proportion of adolescents offered HIV testing among those being tested for common STIs. Statistical process control charts were used to measure performance over time and differentiate common versus special cause variation.Results:We instituted point of care (POC) HIV testing in the PED in January 2012. The proportion of STI tested patients offered HIV testing was increased to >87% and sustained this performance. Implementation of a clinical decision support tool had the highest impact. The majority offered testing agreed, and the most common reason for refusal was a recent negative test. We identified eleven HIV positive patients over 5 years. Eight were newly diagnosed, and 3 had prior positive tests but were not connected to care. All 11 were successfully connected to providers with HIV care expertise.Conclusions:POC HIV testing is feasible, acceptable, and sustainable in a PED setting. The implementation of targeted HIV POC testing in the PED increased the number of HIV tests being offered, the number of high-risk patients being screened, and the number diagnosed and connected to care.

RNA Sequencing in Childhood B-Lymphoblastic Leukemia Improves Molecular and Risk Assignment

Background At diagnosis, recurrent genomic aberrations - aneuploidy and oncogene fusion that drive B-lymphoblastic leukemia - best predict treatment response. Currently, karyotyping and RT-PCR can discern only 50% of the genomic aberrations driving childhood B-ALL. RNA sequencing (RNA-Seq) interrogates the whole transcriptome through deep sequencing. Using RNA-Seq to study expressed SNP variants and expression level of each chromosome, we can identify their copy number; this enables digital karyotyping. For each patient, this digital karyotyping together with oncogene fusion sequencing and transcriptome profiling allow full molecular interrogation of the genomic aberrations that drive leukemia. We molecular subtyped and risk assigned 377 children with B-lymphoblastic leukemia using RNA-Seq. We showed that in childhood B-lymphoblastic leukemia, a single platform RNA-seq significantly improved risk assignment. Methods Whole transcriptome RNA-Seq was performed on the diagnostic bone marrow or peripheral blood samples of 377 children enrolled on the Ma-Spore ALL 2003 and Ma-Spore ALL 2010 studies. Oncogene fusions, variant calling, hierarchical clustering and gross chromosomal copy number calling were performed using RNA-Seq. These are combined for molecular assignment. As compared with conventional risk stratification using a combination of cytogenetics, DNA index and oncogene fusion panel, risk assignment including newly discovered molecular subtypes are made using RNA-Seq. Results Patients are classified into 20 molecularly distinct subtypes (Table 1) in 5 categories: 1. Oncogene fusion category with 10 subtypes. 2. Gene expression profiles with 5 subtypes. 3. Aneuploidy defines 3 subtypes, namely high hyperdiploidy, hypodiploidy and near haploid. 4. Biallelic mutation of PAX5 characterized by PAX5 P80R. 5. B-others. The 20 molecular subtypes are then risk assigned to Low, Intermediate or High risk groups (Table 1). Specifically, 1. Low Risk (LR) - 66% (250/377) of the cohort 2. Intermediate Risk (IR) - 15% (57 of 377) of the cohort 3. High risk (HR) - 12% (44/377) of the cohort 4. B-others - 7% (26/377) of the cohort In the patients with available survival data, compared to 39% by conventional methods, RNA-Seq improves risk assignment by assigning 93% of the total cohort into a distinct risk group (Figure 1). The number of LR patients by RNA-Seq nearly doubled (RNA-Seq n=238 vs conventional n=125), with comparable cumulative incidence of relapse (CIR; 6.2% vs 5.2%) and overall survival (OS; 98.2% vs 99.1%). The number of HR patients also increased &amp;gt;2-fold (RNA-Seq n=41 vs conventional n=17), with a slightly lower CIR (41.2% vs 52.9%) and a similar OS (65.4% vs 64.7%). The RNA-Seq defined risk groups have more significantly distinct outcome (P-value comparing CIR: 1×10-8 vs1×10-7; P-value comparing OS: 2×10-12 vs3×10-7; Figure 1). In conventional risk assignment, 67% of the relapses and 68% of the deaths are in B-Others (61% of patients). Using RNA-Seq, HR (11% of patients) accounts for the most relapses (38%) and deaths (59%) while B-Others (7% of patients) account for 7% of relapses and 5% of deaths. In multivariate analysis using competing risk regression on CIR together with age, gender, WBC and Day 33 MRD, only risk stratification by RNA-Seq and Day 33 MRD remained prognostically significant (RNA-Seq subtype P=6.4×10-4 or 5.9×10-3 for HR or IR vs SR; MRD P=1.3×10-5 or 0.020 for HR or IR vs SR). While in Cox proportional hazards regression on OS, Day 33 MRD lost its significance; RNA-Seq risk stratification is the most significant factor that predicts OS (RNA-Seq subtype P=3.4×10-4 or 0.27 for HR or IR vs SR; MRD P=0.19 or 0.24 for HR or IR vs SR). Conclusion When compared to conventional karyotyping and RT-PCR, in B-lymphoblastic leukemia, RNA-Seq significantly improved molecular diagnosis and risk assignment; it assigns 93% of patients into a distinct molecular and risk group. In Cox proportional hazards regression on OS, Day 33 MRD lost its prognostic significance, and RNA-Seq risk stratification assignment is the only significant predictive factor of overall survival. Disclosures No relevant conflicts of interest to declare.

Biallelic Inactivation of Multiple Tumor Suppressors Is Associated with Early Relapse after Stem Cell Transplant in Newly Diagnosed Myeloma

Biallelic Inactivation of Multiple Tumor Suppressors Is Associated with Early Relapse after Stem Cell Transplant in Newly Diagnosed Myeloma

Present and future of surgicalist system in Korea

As the need for medical services increases, interest in the quality improvement of healthcare and patient safety is also increasing. This study aimed to propose a surgical hospitalist or surgicalist system in Korea. Specifically, it has been suggested that the essential capacities of the surgicalist, including their understanding of surgery, wound management, emergency management, surgical nutrition, and education, may be useful in improving the quality of healthcare and patient safety. The key characteristic of the surgicalist system is that surgeons are “readily available” in the hospital ward to provide primary care for hospitalized patients. Surgicalists provide both perioperative and advanced primary care. As the population ages, the number of high-risk patients who are undergoing major operations increases. The surgicalist system, which is responsible for the perioperative management and advanced primary care of inpatients, is expected to expand rapidly. The shift from the vertical surgeon-resident-centered system to the horizontal surgeon-surgicalist-centered system can help provide high-quality care for patients, and a systematic training system for residents. In addition, it is necessary to define the essential capacities of the surgicalist, and to determine the research and education that can promote them.