The CELLEX is comparable to the UVAR-XTS for the treatment of acute and chronic graft versus host disease (GVHD).

BACKGROUND: Two extracorporeal photopheresis (ECP) instruments, the CELLEX and the UVARXTS are currently being used "off-label" in the US for treatment of graft versus host disease (GVHD). Our study compared the performance of the two instruments in the setting of acute and chronic GVHD. STUDY DESIGN AND METHODS: We retrospectively analyzed the outcomes of patients with steroid refractory or steroid resistant GVHD undergoing ECP at Barnes Jewish Hospital. Multivariate logistic regression was used to evaluate the comparative efficacy of the two instruments with respect to steroid dose reduction (≥50% from baseline) and clinical improvement in GVHD. Chi-square/Fisher exact tests were used to compare the incidence of adverse events, while multivariate Cox regression was employed to assess a potential difference in mortality between the two instrument treatment cohorts. RESULTS: After adjusting for potential confounders, there was no significant difference in the odds of steroid dose reduction (OR = 1.41, 95% confidence interval [CI]: 0.51-3.90, p = 0.50) or clinical improvement (OR 2.0, 95% CI: 0.63-6.41, p = 0.24) between the two instrument treatment cohorts. The frequency of adverse events (CELLEX 45.4%; UVAR XTS 40.5%, p = 0.55) was also comparable between the cohorts. There was no significant difference in mortality of either acute or chronic GVHD patients when treated by the CELLEX as compared to the UVAR-XTS (aHR 0.66, 95% CI: 0.35-1.25, p = 0.20). CONCLUSION: The efficacy and safety of the two ECP instruments, the CELLEX and the UVAR-XTS, are comparable for the treatment of acute and chronic GVHD.

Predictors of Non-Variceal Hemorrhage in a National Cohort of Patients With Chronic Liver Disease.

Background: Non-variceal hemorrhage in patients with chronic liver disease (CLD) increases morbidity, mortality, and healthcare costs. There are limited data on risk factors for non-variceal hemorrhage in the CLD population. The aim of this study was to assess the predictive value of various clinical and laboratory parameters for non-variceal hemorrhage in CLD patients. Methods: We conducted a retrospective cohort study of US veterans diagnosed with CLD between 2002 and 2018 within the Veterans Health Administration database. We derived candidate variables from existing risk prediction models for hemorrhage, risk calculators for severity of liver disease, Charlson index of prognostic comorbidities, and prior literature. We used a competing risk analysis to study the relationship between putative risk factors and incidence of non-variceal hemorrhage in patients with CLD. Results: Of 15,183 CLD patients with no history of cancer or anticoagulation use, 674 experienced non-variceal hemorrhage within 1 year of CLD diagnosis. In multivariable analysis, 11 of the 26 candidate variables independently predicted non-variceal hemorrhage: race, international normalized ratio (INR) > 1.5, bilirubin ≥ 2 mg/dL, albumin ≤ 3.5 g/dL, anemia, alcohol abuse, antiplatelet therapy, chronic kidney disease, dementia, proton pump inhibitor prescription, and recent infection. Conclusions: In this study of almost 15,000 veterans, risk factors for non-variceal bleeding within the first year after diagnosis of CLD included non-Caucasian race, laboratory parameters indicating severe liver disease and recent infection in addition to the risk factors for bleeding observed in a general non-CLD population.

Hospitalizations Among Veterans Treated for Metastatic Prostate Cancer With Abiraterone or Enzalutamide.

BACKGROUND: Abiraterone and enzalutamide are second generation androgen receptor pathway inhibitors (ARPIs) used to treat advanced or metastatic prostate cancer. Without head-to-head comparative studies identifying 1 agent as preferred initial therapy, physician preferences guide initial ARPI choice. This study compares hospitalizations among patients treated initially with abiraterone versus enzalutamide. PATIENTS AND METHODS: United States veterans treated with abiraterone or enzalutamide between May 13, 2011 and December 31, 2019; then compared hospitalization rate during first treatment with ARPI in the Veterans Healthcare Administration. Baseline incidence rate of hospitalization was determined from data 1 year prior to ARPI. Incidence Rate Difference (IRD) was calculated using χ2 test and difference in IRD using Poisson Regression. RESULTS: 19,775 veterans were identified; 13,527 (68.4%) were initially treated with abiraterone and 6248 (31.6%) initially with enzalutamide. The enzalutamide cohort was older (75.8 vs. 74.5 years, P < .001) and had higher baseline comorbidities at ARPI initiation (4.4 vs. 4.0, P < .001). Patients were treated with enzalutamide longer than abiraterone (median 9.0 vs. 8.0 months, P < .001). Total hospitalizations increased from 465 per 1000 person-years in the year prior to treatment with abiraterone to 567 during treatment. Total hospitalizations increased from 417 per 1000 person-years in the year prior to treatment with enzalutamide to 430 during treatment. Total rate of hospitalization increased 22% for abiraterone compared to a 3% increase for enzalutamide in the 12 months after ARPI initiation (P < .0001). Abiraterone was associated with greater increase in rates of acute heart failure, atrial fibrillation, acute kidney injury, urinary tract infections, sepsis, and pneumonia. CONCLUSION: By comparing the rate of hospitalization before vs. during treatment, real world analyses identified a 22% versus 3% increase in hospitalizations with abiraterone compared to enzalutamide respectively, despite being used in a younger population with less comorbid disease. Abiraterone was also associated with higher risk of infections, a novel finding.

Direct oral anticoagulants to treat deep venous thrombosis and pulmonary embolism in patients with cirrhosis: are we there yet?

A 59-year-old female with Child-Pugh class B cirrhosis attributed to nonalcoholic steatohepatitis complicated by hepatic encephalopathy, portal hypertension with esophageal varices, and thrombocytopenia is seen for management of an acute segmental right lower lobe pulmonary embolism in a clinic. She is hemodynamically stable. Complete blood count is notable for hemoglobin 11.6  g/dL and platelets 80 K/µL. Prothrombin time is 12.6 seconds; partial thromboplastin time, 33.7 seconds; and fibrinogen, 221  mg/dL. She was referred to discuss if a direct oral anticoagulant (DOAC) can be used for anticoagulation. What would you suggest?

Different risks of hemorrhage in patients with elevated international normalized ratio from chronic liver disease versus warfarin therapy, a population-based retrospective cohort study.

BACKGROUND: Patients with chronic liver disease (CLD) often present with an elevated international normalized ratio (INR). Although elevated INR reflects a higher risk of hemorrhage among warfarin users, its clinical significance in CLD patients is less clear. OBJECTIVES: We used Veterans Health Administration data to quantify the association between INR and (non-variceal) hemorrhage in patients with CLD compared to warfarin users. METHODS: We performed a multivariate competing risk analysis to study the association between INR and hemorrhage in the two cohorts. We used an interaction term between INR and cohort (CLD/warfarin users) to test if INR had different effects on hemorrhage in the two cohorts. RESULTS: Data from 80 134 patients (14, 412 with CLD and 65, 722 taking warfarin) were analyzed. The effect of INR on the risk of hemorrhage differed between CLD patients and warfarin users (interaction P < .001). As INR increased above 1.5, the adjusted hazard ratio (aHR) for hemorrhage in CLD patients increased to 2.25 but remained fairly constant with further elevation of INR values. In contrast, the risk of hemorrhage in patients taking warfarin remained low with INR in the subtherapeutic (INR <2.0) and therapeutic ranges (INR 2.0-3.0), and increased exponentially with INR in the supratherapeutic range (aHR 1.64 with INR >3.0-3.5, and 4.70 with INR >3.5). CONCLUSIONS: The relationship between INR and risk of hemorrhage in CLD patients is different from that in warfarin users. Caution should be exercised extrapolating data from warfarin users to make clinical decisions in CLD patients.

Statins Reduce Mortality in Multiple Myeloma: A Population-Based US Study.

BACKGROUND: We studied the effect of statins on mortality in a nationally representative sample of patients with multiple myeloma, and explored the benefit of statins in a subgroup of patients treated with novel agents. METHODS: Patients diagnosed with multiple myeloma between 2007 and 2013 were identified in the SEER-Medicare database using International Classification of Diseases (ICD)-03 codes. ICD-9 and Healthcare Common Procedure Coding System codes were used to identify comorbidities and treatments. We assessed the association of statins with mortality in patients with multiple myeloma using multivariate Cox proportional hazards regression analysis. For subanalysis, we used the same statistical technique to investigate the effect of statins on mortality in myeloma patients treated with novel agents. RESULTS: A total of 5922 patients were diagnosed with multiple myeloma within the study period. Use of statins was associated with 21% reduction in risk of death (adjusted hazard ratio [aHR] 0.79; 95% confidence interval [CI] 0.74-0.84) among all patients with multiple myeloma. Among the patents treated with novel agents (n = 3603), statins reduced mortality by 10% (aHR = 0.90, 95% CI 0.83-0.98). CONCLUSIONS: Use of statins is likely associated with lower mortality in patients with multiple myeloma.

Venous thromboembolism in multiple myeloma is associated with increased mortality.

BACKGROUND: In multiple myeloma, venous thromboembolism (VTE) is common, and treatments for myeloma, such as lenalidomide, increase the risk of thrombosis while improving survival. The association between VTE and survival is not well known. OBJECTIVES: To determine the association between VTE and survival in multiple myeloma (MM) while adjusting for known confounders that affect risk of thrombosis and survival, including patient characteristics and treatment in a retrospective cohort of US veterans. PATIENTS/METHODS: A cohort of patients with newly diagnosed MM treated within Veterans Health Administration between September 1, 1999, and June 30, 2014, was created to assess the association between VTE and mortality using Cox proportional hazards regression modeling while accounting for known prognostic factors and treatments. RESULTS: The cohort comprised 4446 patients with myeloma, including 2837 patients diagnosed after lenalidomide approval in July 2006. VTE occurred in 327 (7.4%) patients within 1 year and occurred at a median of 77 days (interquartile range, 37-153) after starting therapy for MM. In all patients, VTE was associated with increased mortality at 6 months (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.18-2.37). Patients in the post-lenalidomide cohort with VTE had an increased mortality at both 6 months (aHR, 2.31; 95% CI, 1.52-3.51) and 12 months (aHR, 1.66; 95% CI, 1.19-2.33) after treatment initiation. DISCUSSION: This study shows that VTE during the first 6-12 months of therapy is associated with increased mortality in patients with MM. Studies evaluating thromboprophylaxis in patients at high risk of thrombosis are needed.

Splanchnic vein thrombosis predicts worse survival in patients with advanced pancreatic cancer.

INTRODUCTION: Pancreatic cancer is a thrombogenic malignancy with nearly half of venous thrombotic events occurring in the splanchnic circulation. The effect of splanchnic vein thrombosis on mortality in pancreatic cancer is unknown. We studied the effect of splanchnic vein thrombosis on mortality in veterans with advanced pancreatic adenocarcinoma, and explored the association of anticoagulant therapy on mortality and hemorrhage. METHODS: Using International Classification of Diseases (ICD) codes, we identified eligible patients and outcomes in the Veterans Health Administration database. Using Cox proportional hazards regression, we analyzed the association between splanchnic vein thrombosis and mortality among patients with advanced pancreatic cancer. We used propensity score inverse probability-of-treatment weighting to balance the groups who did and did not receive anticoagulation. To understand the role of anticoagulant therapy, we used Cox proportional hazards regression to analyze mortality and competing risk analysis to assess the risk of hemorrhage. RESULTS: Of the patients with advanced pancreatic cancer (N = 6164), 122 developed splanchnic vein thrombosis. Splanchnic vein thrombosis was associated with a two-fold increase in mortality, aHR 2.02, 95% CI 1.65-2.47. The finding held true after restricting the analysis to patients undergoing treatment for pancreatic cancer, and after adjusting for immortal time bias by a 30-day landmark analysis. Anticoagulant therapy did not affect mortality (aHR 0.99, 95% CI 0.65-1.51), and increased the risk of hemorrhage (aHR 2.7, 95% CI 1.02-7.07). CONCLUSION: Splanchnic vein thrombosis predicts worse survival in patients with advanced pancreatic adenocarcinoma. Anticoagulant therapy may not mitigate this increased mortality, and increases the risk of hemorrhage.

Prognostication in Philadelphia Chromosome Negative Myeloproliferative Neoplasms: a Review of the Recent Literature.

PURPOSE OF REVIEW: The prognosis for patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is highly variable. All Ph-negative MPNs carry an increased risk for thrombotic complications, bleeding, and leukemic transformation. Several clinical, biological, and molecular prognostic factors have been identified in recent years, which provide important information in guiding management of patients with Ph-negative MPNs. In this review, we critically evaluate the recent published literature and discuss important new developments in clinical and molecular factors that impact survival, disease transformation, and thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis. RECENT FINDINGS: Recent studies have identified several clinical factors and non-driver mutations to have prognostic impact on Ph-negative MPNs independent of conventional risk stratification and prognostic models. In polycythemia vera (PV), leukocytosis, abnormal karyotype, phlebotomy requirement on hydroxyurea, increased bone marrow fibrosis, and mutations in ASXL1, SRSF2, and IDH2 were identified as additional adverse prognostic factors. In essential thrombocythemia (ET), JAK2 V617F mutation, splenomegaly, and mutations in SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2 were found to be additional negative prognostic factors. Bone marrow fibrosis and mutations in ASXL1, SRSF2, EZH2, and IDH1/2 have been found to be additional prognostic factors in primary myelofibrosis (PMF). CALR mutations appear to be a favorable prognostic factor in PMF, which has not been clearly demonstrated in ET. The prognosis for patients with PV, ET, and PMF is dependent upon the presence or absence of several clinical, biological, and molecular risk factors. The significance of additional risk factors identified in these recent studies will need further validation in prospective studies to determine how they may be best utilized in the management of these disorders.