Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

Exploratory analysis of the spatial distribution of adult glioma age-adjusted county incidence rates, Nebraska Medicine, 2009-2019.

Background: Central nervous system (CNS) cancers including gliomas have low incidence but high mortality. The age-adjusted incidence rate for CNS cancers is higher in Nebraska than nationally. This exploratory study was motivated by glioma patient inquiries about possible clustering of cases within the state to see if more in-depth investigation was warranted. Methods: Using electronic health records from Nebraska Medicine, we identified Nebraska adult (age ≥19) glioma patients diagnosed between January 1, 2009 and November 1, 2019. Patient residential addresses were geocoded, mapped, and combined with annual US Census data to compute age-adjusted incidence rates (AAIR) at the county level. Counties with fewer than five cases were excluded to protect patient identity. ArcGIS software was used for geocoding and mapping. Results: Of the 285 cases included in the analysis, 53.2% were geocoded with exact match and the remainder were processed manually. Cases occurred in 47 of the 93 counties. After data suppression, 11 counties (228 cases) visually clustered in eastern and central Nebraska with AAIR ranging from 0.85 to 5.66 per 100 000. Conclusions: Many counties in the state were excluded from analysis of this rare cancer due to the small number of cases leading to unstable rates and the need to suppress data to protect patient privacy. However, this preliminary study suggests that glioma incidence is highest in central and eastern Nebraska. Next steps include analysis of state cancer registry data to ensure more complete case ascertainment.

Overall Survival and Prognostic Factors in Metastatic Triple-Negative Breast Cancer: A National Cancer Database Analysis.

BACKGROUND: Metastatic triple-negative breast cancer (TNBC) is aggressive with poor median overall survival (OS) ranging from 8 to 13 months. There exists considerable heterogeneity in survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival, utilizing a large patient sample from the National Cancer Database (NCDB). METHODS: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinicopathological, and treatment data and overall survival (OS) outcomes were collected. Kaplan-Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. RESULTS: In this sample, 2273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on OS. CONCLUSIONS: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help individualize prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials.

Risk factors for venous thromboembolism in hospitalized patients with hematological malignancy: an analysis of the National Inpatient Sample, 2011-2015.

Hospitalized patients with hematological malignancy (HM) suffer an increased incidence of venous thromboembolism (VTE). We sought to identify risk factors and rate of VTE in hospitalized patients with HM using National Inpatient Sample (NIS) for the years 2011 to 2015. We used ICD-9 codes to identify patients with HM as the primary diagnosis and VTE as a secondary diagnosis for hospitalization. The rate of VTE was highest in patients with acute myeloid leukemia (6.6%) followed by acute lymphocytic leukemia (6.1%) and non-Hodgkin's lymphoma (6.0%). The highest risk of VTE occurred among patients with HM receiving chemotherapy (OR 1.68; 95% CI 1.567-1.809) followed by infection such as pneumonia (OR 1.31; 95% CI 1.201-1.436) and sepsis (OR = 1.66; 95% CI = 1.524-1.621). Chemotherapy had the highest risk of developing VTE during hospitalization followed by sepsis and pneumonia. The identification of patients with HM most at risk for VTE could be used to design and test prophylactic strategy.

Aggressive Disease and Rare Sequelae in a Unique Case of Atypical Hemolytic Uremic Syndrome Secondary to Adult Onset Still's Disease.

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) which generally presents as a triad of thrombocytopenia, hemolytic anemia and renal failure. We present the case of a 69-year-old woman with ongoing fevers, arthralgias, diffuse rash and pharyngitis for 3 months. Investigation revealed an elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and ferritin; however, autoimmune and infectious studies were unremarkable, raising the suspicion for adult onset Still's disease (AOSD). Before out patient therapy could be initiated, she presented to our emergency room (ER) with a grand mal seizure and persistence of her initial triad of fevers, arthralgias and rash. Evaluation revealed non-immune hemolytic anemia, thrombocytopenia, and abnormal renal function consistent with TMA and the patient was subsequently started on plasmapheresis, hemodialysis and corticosteroid therapy. ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-13 activity was 38%, ruling out thrombotic thrombocytopenic purpura (TTP). A kidney biopsy demonstrated glomerular changes of TMA and a diagnosis of secondary aHUS triggered by AOSD was established. The patient was treated with eculizumab and high dose steroids with improvement in her laboratory values, eventually becoming hemodialysis-independent. This case highlights the clinical urgency in the prompt recognition of AOSD, a potent inflammatory disorder, which when co-existing with a complement- dysregulatory defect, can significantly augment TMA disease severity.