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Background: Oral decitabine/cedazuridine (ASTX727) is a fixed dose combination of decitabine (35 mg) and the cytidine deaminase inhibitor cedazuridine (100 mg) given once daily X 5 days on a 28-day cycle producing pharmacokinetic (PK) exposure equivalent to the standard intravenous (IV) decitabine regimen of 20 mg/m 2 daily X 5 days on a 28-day cycle. This was demonstrated in the pivotal ASCERTAIN study (Garcia-Manero, et al, ASH 2019) as it provided a PK bridge to existing decitabine data and demonstrated median OS was 31.7 mo. (Savona,et al. Intl. MDSF International Congress on MDS, 2021). Subjects were initially classified by the International Prognosis Scoring System (IPSS) for historical reasons, however IPSS-R and IPSS-M are enhancements to IPSS that provide dynamic risk assessment for predicting clinical outcomes in MDS. Here, the objective was to re-classify the MDS subjects enrolled on the ASCERTAIN study by IPSS-R and IPSS-M and measure the impact of informing patient outcomes based on re-calculated risk assessment. Methods: One hundred thirty-three subjects with MDS/CMML (chronic myelomonocytic leukemia) were enrolled in ASCERTAIN and were randomly assigned either IV decitabine for cycle 1 and oral decitabine/cedazuridine for cycle 2 or the opposite treatment sequence. All subjects continuing beyond cycle 2 received oral decitabine/cedazuridine for all subsequent cycles until treatment discontinuation for disease progression, toxicity, patient's decision, or HSCT. Whole blood collected prior to treatment was used for DNA isolation and molecular abnormalities identified using next-generation sequencing (NGS) hematologic malignancy panel of 179 genes including all genes commonly mutated in MDS. In the initial analysis of clinical outcomes, subjects were classified by IPSS with response assessment by IWG 2006 IPSS low and Int-1 risk levels were categorized as lower-risk MDS (LR-MDS), whereas IPSS Int-2 and high-risk categories were categorized as higher-risk MDS (HR-MDS). Subjects with sufficient data based on (e.g., available heme parameters, cytogenetics, NGS etc.) were reclassified by IPSS-R and IPSS-M. Subjects with IPSS-R score of ≤3.5 or IPSS-M of either very low, low, or moderate low were categorized as LR-MDS. Similarly subjects with IPSS-R score of >3.5 or an IPSS-M categorization of either moderate high, high, or very high were categorized as HR-MDS. Reclassified subjects were reassessed for CR (Complete Response), OS, and LFS and Harrell's concordance index (c-index) was used to describe the level of agreement between each scale and outcomes. Results: Based on the available data, the number of MDS subjects in the different risk classifications were the following: IPSS: 117, IPSS-R: 104, and IPSS-M: 105. Thirteen and 12 subjects on the IPSS could not be reclassified in the IPSS-R and IPSS-M, respectively, including 5 Int-1 and 2 low-risk MDS cases. CMML subjects were excluded from these analyses. Re-classification generally resulted in the upgrade of the subjects from LR-MDS to HR-MDS (Fig. 1). Thirty-one (26.5%) subjects from IPSS were reallocated in the IPSS-R to different risk categories; 3 (9.7%) were downgraded and 28 (90.3%) were upgraded. Similarly on reclassification with IPSS-M 34 (32.4%) of the patients reclassified; 5 (14.8%) were downgraded and 29 (85.3%) were upgraded. For IPSS LR-MDS, 23.2% of patients achieved CR, and 22.9% in the IPSS HR-MDS. Similarly, 21.6% patients achieved CR in the IPSS-R LR-MDS, and 23.9% in the IPSS-R HR-MDS; 26.3% patients achieved CR in the IPSS-M LR-MDS, and 20.9% in the IPSS-M HR-MDS. The c-index for the IPSS was .64 (OS) and .67 (LFS), IPSS-R was .70 (OS) and .71 (LFS), and .75 (OS) and .78 (LFS) for the IPSS-M (Table1). Conclusion: Reclassification from IPSS to IPSS-R or IPSS-M upgraded multiple subjects from a LR to a HR category, describing the ASCERTAIN patient population as a majority higher risk population with worse prognosis than previously assumed based on the IPSS. The efficacy as measured by the CR rates did not change when the LR and HR categories were defined by the different risk stratification systems. In contrast, the c-index improves with migration from IPSS to IPSS-R to IPSS-M, indicating an increased discriminatory ability of IPSS-M score in comparison to IPSS and IPSS-R, to predict patient outcomes.

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.

ImportanceLittle is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments.ObjectiveTo investigate how often patients with low–recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival.Design, Setting, and ParticipantsIn this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX 21-gene Breast Recurrence Score assay result of no more than 25, were randomized to endocrine therapy alone vs chemotherapy then endocrine therapy. Prospectively collected radiotherapy information was collected from 4871 patients treated in diverse settings. Data were analyzed June 2022 to April 2023.ExposureReceipt of RNI (targeting at least the supraclavicular region).Main Outcome(s) and Measure(s)Cumulative incidence of LRR was calculated by locoregional treatment received. Analyses were assessed for associations between invasive disease-free survival (IDFS) and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery. Radiotherapy information was recorded in the first year after randomization, so survival analyses were landmarked as starting at 1 year among those still at risk.ResultsOf 4871 female patients (median [range] age, 57 [18-87] years) with radiotherapy forms, 3947 (81.0%) reported radiotherapy receipt. Of 3852 patients who received radiotherapy and had complete information on targets, 2274 (59.0%) received RNI. With a median follow-up of 6.1 years, the cumulative incidence of LRR by 5 years was 0.85% among patients who received breast-conserving surgery and radiotherapy with RNI; 0.55% after breast-conserving surgery with radiotherapy without RNI; 0.11% after mastectomy with postmastectomy radiotherapy; and 1.7% after mastectomy without radiotherapy. Similarly low LRR was observed within the group assigned to endocrine therapy without chemotherapy. The rate of IDFS did not differ by RNI receipt (premenopausal: hazard ratio [HR], 1.03; 95% CI, 0.74-1.43; P = .87; postmenopausal: HR, 0.85; 95% CI, 0.68-1.07; P = .16).Conclusions and RelevanceIn this secondary analysis of a clinical trial, RNI use was divided in the setting of biologically favorable N1 disease, and rates of LRR were low even in patients who did not receive RNI. Disease-free survival was not associated with RNI receipt; omission of chemotherapy among patients similar to those enrolled in the S1007 trial is not an independent indication for use of RNI.

Background Individuals with non-English language preferences (NELP) represent a growing proportion of the USA population. Prior studies demonstrate disparate health outcomes related to NELP status; however, this patient population is often excluded from medical research. There is a paucity of literature describing the impact of NELP status on trauma, specifically injury and outcomes related to vehicle occupants injured during motor vehicle collisions (MVCs). The goal of this study was to evaluate the representation of patients with NELP in both emergency medicine and trauma literature. Methods We conducted a systematic search of US-based publications from 2010 to 2021. Titles, abstracts and full texts of eligible articles were evaluated. Data were extracted using an a priori determined standardised reporting tool to evaluate language as study inclusion/exclusion criteria, manuscript reporting of language, assessment of language as a primary variable and consideration of language in study methodology. Results A total of 82 studies met inclusion criteria. Twenty-three studies (28%) excluded NELP populations and only one study explicitly included the NELP population. None of the studies evaluated language as a primary outcome of the study or included language as a variable in the analysis. Over half of the studies (53.6%) used a public data set or registry. Conclusion NELP populations are routinely excluded from and are difficult to identify in MVC trauma research. Without appropriate inclusion and identification, it will be difficult to understand the prevalence and outcomes of traumatic injury in NELP patients and to develop culturally and linguistically appropriate interventions.