Search

Malignancy is a well-known risk factor for venous thromboembolism (VTE), and the Khorana risk score is effective for screening patients with solid tumors. However, there is a lack of validated screening tools and established risk factors for patients undergoing hematopoietic stem cell transplantation (HCT). Current literature reports a 2.5% to 8.5% incidence of VTE in HCT recipients. Anticoagulation is difficult to manage post-transplantation, given prolonged thrombocytopenia and the likelihood of bleeding. By identifying risk factors, a predictive model may be developed to prospectively test prophylaxis strategies in patients at the highest risk of a thromboembolic event (TE). This retrospective single-center study evaluated the cumulative incidence of TE at 6 months following allogeneic or autologous HCT in adult subjects undergoing transplantation between March 2014 and December 2019. The study also aimed to identify risk factors for developing a TE, evaluate the time from HCT to TE, and compare 1-year survival following HCT between patients with a TE and those without a TE. In evaluating the incidence of TE, ICD-9 and ICD-10 codes were used to determine cancer diagnosis, TE events occurring up 180 days after HCT, and comorbidities of interest. Each subject was reviewed for data accuracy by a manual retrospective chart review. Statistical tests including the cumulative incidence method with competing risks, Gray's test, and univariate and multivariate Cox proportional hazards models were used to analyze the time to first TE, evaluate risk factors, and assess 1-year survival post-HCT in relation to TEs occurring within 180 days of HCT. Variables examined included age, sex, body mass index, transplant type, hospital length of stay (LOS), history of TE prior to transplantation, active infections, graft-versus-host disease (GVHD), veno-occlusive disorder, cytomegalovirus serostatus, and other factors. The study included 636 evaluable patients; the majority were male (57.9%) and white (68.7%) and had undergone autologous HCT (68.4%). Twenty-nine patients (4.6%) experienced a TE within 180 days post-transplantation. TEs were more common in the allogeneic HCT recipients (n = 13/201; 6.5%) compared to the autologous HCT recipients (n = 16/435; 3.7%; P = .122). The cumulative incidence of TE was higher in patients who developed an active infection compared to those who did not (7.6% versus 3.1%; P = .011). Hospital LOS (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.0 to 1.06; P = .036) and active infection (HR, 2.34; 95% CI, 1.1 to 4.95; P = .027) were significantly associated with TE in univariate analysis but were not retained in the final multivariate model. There was no difference in 1-year survival between all patients who experienced a TE and those who did not; however, in the autologous HCT group, 1-year survival rate was significantly lower in patients with a TE compared to those without TE (80.4% versus 95.3%; P = .01) (Figure 3C). None of the examined variables, including a history of TE and GVHD, were associated with TE risk. Although the overall incidence of TE in our study was low, many patients received pharmacologic or mechanical prophylaxis, suggesting that such strategies may be effective in mitigating TE risk. Such factors as infection and hospital LOS may further increase TE risk. Providers should continuously monitor for risk factors and signs and symptoms of TE post-transplantation. It is also imperative to consider chemical prophylaxis if counts are recovered during hospitalization., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

CYP2C19-guided voriconazole dosing reduces pharmacokinetic variability, but many patients remain subtherapeutic. The aim of this study was to evaluate the effect of candidate genes and a novel CYP2C haplotype on voriconazole trough concentrations in patients receiving CYP2C19-guided dosing. This is a retrospective candidate gene study in allogeneic hematopoietic cell transplant (HCT) patients receiving CYP2C19-guided voriconazole dosing. Patients were genotyped for ABCB1, ABCG2, CYP2C9, CYP3A4, CYP3A5, and the CYP2C haplotype. Of 185 patients, 36% were subtherapeutic (of which 79% were normal or intermediate metabolizers). In all patients, CYP2C19 (p < 0.001), age (p = 0.018), and letermovir use (p = 0.001) were associated with voriconazole concentrations. In the subset receiving 200 mg daily (non-RM/UMs), CYP2C19 (p = 0.004) and ABCG2 (p = 0.015) were associated with voriconazole concentrations; CYP2C19 (p = 0.028) and letermovir use (p = 0.001) were associated with subtherapeutic status. CYP2C19 phenotype and letermovir use were significantly associated with subtherapeutic voriconazole concentrations and may be used to improve voriconazole precision dosing, while further research is needed to clarify the role of ABCG2 in voriconazole dosing., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: There is a paucity of real-world data on opioid screening and urine toxicology testing in outpatient oncology palliative medicine., Methods: This was a retrospective analysis of adult patients with cancer completing ≥ one outpatient palliative medicine visit and the Edmonton Symptom Assessment Scale (ESAS). Patient demographics, the Screener and Opioid Assessment for Patients with Pain-Short Form (SOAPP-SF), ESAS, medications, and urine toxicology screens (UTSs) were collected at baseline and follow-up visits. The primary end point was the frequency and type(s) of noncompliant UTSs (ie, presence of a nonprescribed substance or absence of a prescribed substance). Secondarily, risk factors for noncompliant UTSs were evaluated using univariate and multivariable logistic regression., Results: Of 189 evaluable patients (632 clinic visits), 113 underwent ≥one UTSs, 125 SOAPP-SF, and 75 had both. The median age was 56 (range, 26-80) years, 56% were female, 58% were White, 40% were Black, 48% had stage IV disease, the median baseline pain score was 7, and the median SOAPP-SF was 3. Oxycodone was the most prescribed drug (n = 125). Of 113 patients who underwent UTSs, 54% (n = 61) had ≥one noncompliant result. Thirty-nine percent (n = 44) had a total of 128 noncompliant results for the presence of a nonprescribed substance; 29% (n = 33) had a total of 53 noncompliant results for the absence of a prescribed substance. SOAPP-SF Q4 (use of illegal drugs) (odds ratio [OR], 3.61; 95% CI, 1.81 to 7.19; P < .001) and prescription with nonopioid adjuvant medications (OR, 2.83; 95% CI, 1.12 to 7.19; P = .029) were associated with increased odds of a noncompliant UTS., Conclusion: More than half of the tested population had noncompliant UTS. Screening and evaluating risk factors for nonmedical opioid use is critical in oncology palliative medicine.

Cancer-related symptoms, like depression, nausea, and pain, are common and negatively affect quality of life. Unfortunately, there is large inter-individual variability in response to supportive care medications for these symptoms. Pharmacogenomics may inform prescribing by identification of those genetically at risk for drug related adverse events or therapeutic failure. While such information can be applied to many drugs, there are specific oncology populations that could greatly benefit from pharmacogenomics-guided supportive care management due to high symptom burden, including those receiving palliative medicine and hematopoietic stem cell transplantation. The goal of this paper is to provide an overview of, and lessons learned from, the development of two prospective pharmacogenomics-guided interventional trials ("Supportive Care PGx Trial" and "Transplant PGx Trial") across two different clinical settings at the Levine Cancer Institute: the Department of Supportive Oncology and the Transplant and Cellular Therapy section. Key considerations included the appropriate study design and endpoints (balancing study goals and resources), dissemination and application of individual pharmacogenetics results, technical details about assay development, and overall care coordination to minimize clinic disruption., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: We evaluated time to thromboembolism (TE) and risk factors in multiple myeloma (MM) patients after first exposure to immunomodulatory therapy, stratified by thromboprophylaxis., Patients and Methods: We retrospectively analyzed adult MM patients who received immunomodulatory therapy with or without dexamethasone between February 2012 and October 2017. Thromboprophylaxis included aspirin, anticoagulants (low-molecular-weight heparin, direct oral anticoagulants, or warfarin), or none. Primary endpoint was time to on-treatment TE by thromboprophylaxis type. Time to TE using death as a competing risk censored at 12 months was used in univariate and multivariable analyses to identify risk factors., Results: Of 485 evaluable patients, 57% were white and 36% African American; median age was 66. Most received lenalidomide (97.5%) and dexamethasone (90%). Half presented with ≥ 1 comorbidities. Sixty-nine had no documented receipt of prophylaxis, 357 aspirin, and 59 anticoagulation. More patients receiving anticoagulants had ≥ 1 comorbidities compared to aspirin or no-prophylaxis groups (P < .001). There was no difference in 12-month estimated cumulative incidence of TE (7.3%; 95% confidence interval, 5.2-9.9) between thromboprophylaxis groups (none 4.4%, aspirin 8.5%, anticoagulant 3.4%) (P = .24). In multivariable analyses, male sex (hazard ratio, 2.50; 95% confidence interval, 1.21-5.17; P = .014) and presence of any comorbidity (hazard ratio, 2.35; 95% confidence interval, 1.17-4.73; P = .016) were associated with TE incidence; thromboprophylaxis type was not (P = .12)., Conclusion: Male sex and presence of any comorbidity were associated with time to TE. There were no differences in TE incidence between thromboprophylaxis groups despite a higher proportion of those in the anticoagulant group having ≥ 1 comorbidities., (Copyright © 2020 Elsevier Inc. All rights reserved.)