Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis.

BACKGROUND: In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil. METHODS: In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause. RESULTS: In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P = 0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups. CONCLUSIONS: Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. (Funded by the National Heart, Lung, and Blood Institute and others; BMT CTN 1703 ClinicalTrials.gov number, NCT03959241.).

Adaptation of Remote Symptom Monitoring Using Electronic Patient-Reported Outcomes for Implementation in Real-World Settings.

PURPOSE: Despite evidence of clinical benefits, widespread implementation of remote symptom monitoring has been limited. We describe a process of adapting a remote symptom monitoring intervention developed in a research setting to a real-world clinical setting at two cancer centers. METHODS: This formative evaluation assessed core components and adaptations to improve acceptability and fit of remote symptom monitoring using Stirman's Framework for Modifications and Adaptations. Implementation outcomes were evaluated in pilot studies at the two cancer centers testing technology (phase I) and workflow (phase II and III) using electronic health data; qualitative evaluation with semistructured interviews of clinical team members; and capture of field notes from clinical teams and administrators regarding barriers and recommended adaptations for future implementation. RESULTS: Core components of remote symptom monitoring included electronic delivery of surveys with actionable symptoms, patient education on the intervention, a system to monitor survey compliance in real time, the capacity to generate alerts, training nurses to manage alerts, and identification of personnel responsible for managing symptoms. In the pilot studies, while most patients completed > 50% of expected surveys, adaptations were identified to address barriers related to workflow challenges, patient and clinician access to technology, digital health literacy, survey fatigue, alert fatigue, and data visibility. CONCLUSION: Using an implementation science approach, we facilitated adaptation of remote symptom monitoring interventions from the research setting to clinical practice and identified key areas to promote effective uptake and sustainability.

Impact of sociodemographic factors on early mortality in acute promyelocytic leukemia in the United States: A time-trend analysis.

BACKGROUND: The survival of patients with acute promyelocytic leukemia (APL) has dramatically improved with the use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, because of the complexity of the initial management, early mortality (EM) remains a major contributor to treatment failure. It is less known whether advances in treatment, urgent access to specialized care, and broad availability of ATRA/ATO have reduced EM in the last 2 decades. Furthermore, the influence of sociodemographic factors on the risk of EM also remains unclear. METHODS: This study used the Surveillance, Epidemiology, and End Results program to characterize the impact of sociodemographic factors on the rates of EM and overall survival (OS) in patients with APL diagnosed between 1992 and 2015. RESULTS: In all, 2224 cases were identified (895 who were younger than 40 years and 1329 who were 40 years old or older); 47.9% had a county-level median household income of $59,630 or higher, 49.0% belonged to counties where more than 31% of adults held at least a bachelor's degree, and 86.0% resided in urban areas. The rate of EM declined from 31.5% in 1992-1995 to 15.9% in 2012-2015 for all patients. It improved for patients younger than 40 years (27.4% in 1992-1995 vs 5.4% in 2012-2015; P < .001) and for patients 40 years old or older but not to the same extent (35.2% in 1992-1995 vs 22.2% in 2012-2015; P = .02). Importantly, improvements in EM were not seen among patients residing in rural areas, with the rate remaining higher than 20% in 2012-2015. The 3-year OS rate was 49.2% for patients with APL diagnosed in 1992-1995 and 76.4% for patients diagnosed in 2012-2015. CONCLUSIONS: These findings confirm consistent improvements in EM and OS for patients with APL and point to the challenge of further extending these improvements in EM rates to older patients and to those living in rural areas.

Impact of insurance status on the survival of younger patients diagnosed with acute promyelocytic leukemia in the United States.

BACKGROUND: Survival among patients diagnosed with acute promyelocytic leukemia (APL) has significantly improved with the use of all-trans retinoic acid and arsenic trioxide. However, the need for immediate diagnosis and access to specialized care and the cost associated with APL management can potentially act as barriers for disadvantaged patients. The influence of sociodemographic factors on the outcomes of patients with APL remains unclear. METHODS: The authors used the National Cancer Institute's Surveillance, Epidemiology, and End Results program to characterize the impact of sociodemographic factors on survival in patients younger than 65 years with APL. RESULTS: The authors identified 1787 cases: 816 who were younger than 40 years and 971 who were 40 years old or older. Insured patients who were younger than 40 years had an improved 5-year overall survival (OS) rate in comparison with patients without insurance. Among patients who were 40 years or older, having insurance (other than Medicaid) was associated with better survival than being a Medicaid beneficiary or being uninsured, whereas patients with Medicaid had improved 5-year OS in comparison with uninsured patients. In a multivariate analysis of patients younger than 40 years, a higher risk of death was associated with being male, being diagnosed in earlier years, and being uninsured. For patients who were 40 years old or older, mortality increased with increasing age and for both Medicaid and uninsured patients in comparison with insured patients. CONCLUSIONS: Despite the high cure rate experienced by patients with APL, patients younger than 65 years without insurance and those 40 years old or older with Medicaid are at a significant disadvantage in comparison with patients with insurance. These findings point to an opportunity to improve survival in APL by addressing access to care.

Pleural epitheliod hemangioendothelioma: What started as a liver fluke and ended up being almost mistaken for malignant mesothelioma.

Epitheliod hemangioendothelioma (EHE) is a rare tumor of vascular origin. The pleural variant has only been reported around 20 times in English literature. It commonly occurs in older men and carries a poor prognosis with average survival lasting from a few weeks to months. Pleural EHE (PEHE) can be a diagnostic challenge due to its rarity as well as similarities to other pleural and vascular tumors. There is currently no standard treatment for EHE. Due to the rarity of this disease, reaching a final diagnosis is challenging. It's clinical, radiological, and pathological resemblance to malignant mesothelioma can cause a delay in diagnosis. Special stains such as CD31, CD34, and factor VIII related antigen can help differentiate between the two. Ordering appropriate stains in a timely manner can help avoid misdiagnosing PEHE.

Early complications after biliary enteric anastomosis for benign diseases: a retrospective analysis.

BACKGROUND: Biliary-enteric anastomosis (BEA) is a common surgical procedure performed for the management of biliary obstruction or leakage that results from a variety of benign and malignant diseases. Complications following BEA are not rare. We aimed to determine the incidence and the factors associated with early complications occurring after BEA for benign diseases. METHODS: We reviewed the medical records of all patients who underwent BEA for benign diseases at our institution between January 1988 and December 2009. The primary outcome was early post operative complication. Logistic regression analysis was done to identify factors predicting the occurrence of complications. RESULTS: Records of 79 patients were reviewed. There were 34 (43%) males and 45 (57% females). Majority (53%) had choledocholithiasis with impacted stone or distal stricture, followed by traumatic injury to the biliary system (33%). Thirty-four patients (43%) underwent a hepaticojejunostomy, 19 patients (24%) underwent a choledochojejunostomy, and choledochoduodenostomy was performed in 26 patients (33%). Early complications occurred in 39 (49%) patients - 41% had local complications and 25% had systemic complications. Most frequent complications were wound infection (23%) and bile leak (10%). Four (5%) patients died. On multivariate analysis, low serum albumin level (odds ratio = 16, 95% CI = 1.14-234.6) and higher ASA levels (odds ratio = 7, 95% CI: 1.22-33.34) were the independent factors predicting the early complications following BEA. CONCLUSIONS: Half of the patients who underwent BEA for benign diseases had complications in our population. This high incidence may be explained by the high incidence of hypoalbuminemia and the high-risk group who underwent operation.