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Aim:Identify oncology healthcare providers' attitudes toward barriers to and use cases for pharmacogenomic (PGx) testing and implications for prescribing anticancer and supportive care medications. Materials & methods:A questionnaire was designed and disseminated to 71 practicing oncology providers across the MedStar Health System. Results:25 of 70 (36%) eligible oncology providers were included. 88% were aware of PGx testing and 72% believed PGx can improve care. Of providers who had ordered a medication with PGx implications in the past month, interest in PGx for anticancer (90–100%) and supportive care medications (>75%) was high. Providers with previous PGx education were more likely to have ordered a test (odds ratio: 7.9; 95% CI: 1.1–56; p = 0.0394). Conclusion:Oncology provider prescribing practices and interest in PGx suggest opportunities for implementation.

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). The optimal bridging therapy is unknown in this setting.

•Low-dose IL-2 is safe and well tolerated at variable dosing regimens in pediatric patients with steroid-refractory chronic GVHD.•Low-dose IL-2 is effective in combination with other immunosuppressive medications.

Relapse is the most common cause of mortality in acute myeloid leukemia (AML) patients after allogeneic stem cell transplant (SCT). Post-SCT maintenance strategies that prevent relapse are desirable but must be well tolerated and convenient to administer. We hypothesized single agent venetoclax (ven) may be an effective maintenance therapy among high relapse risk patients. Between February 2019 and December 2021, we administered post-SCT ven maintenance to 49 AML patients at high-risk for relapse as a prospectively defined off-label practice at our institution. Ven was planned to be administered until 1-year post-SCT. While temporary interruptions were common (67.3% of all patients), of those with >1 year follow up, 22/25 (88%) completed the full year of planned therapy. Cytopenias (40.8%) and gastrointestinal adverse events (34.7%) were the most common toxicities. At 1-year post-SCT, overall survival (OS) and relapse-free survival (RFS) were 70% and 67% respectively. Our experience demonstrates single agent ven is a safe, tolerable, and feasible maintenance therapy that may improve RFS and OS in high relapse risk post-SCT patients.

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by a mutation in the NF2suppressor gene and is characterized by the development of multiple benign tumors throughout the central nervous system. Bilateral vestibular schwannomas (VSs) are pathognomonic for NF2 and are associated with progressive hearing loss and eventual deafness in most patients. This review presents current management options for NF-2-associated VSs.

The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult. Therefore, we aimed to establish a novel donor-screening program to generate responder-derived FMT for use in PD-1 refractory melanoma. Candidate PD-1 responder donors and PD-1 refractory recipients were recruited via clinic-based encounters at the University of Pittsburgh Medical Center hospitals. Eligible donors and recipients underwent physician assessment and screening of serum, stool and nasopharynx for transmissible agents, which included SARS-CoV-2 modification. The cost of donor and recipient screening was calculated. Initially, 29 donors were screened with 14 eligible donors identified after exclusion; of the 14 donors, eight were utilized in clinical trials. The overall efficiency of screening was 48%. Seroprevalence rates for cytomegalovirus, Epstein-Barr virus, HSV-2, HHV-6, HTLV-1, HTLV-2, and syphilis were similar to published statistics from healthy blood donors in the USA. Donor stool studies indicated a 3.6% incidence of E. histolytica and norovirus, 3.7% incidence of giardia and 7.1% incidence of C. difficile. A single donor tested positive for SARS-CoV-2 in stool only. The cost for finding a single eligible donor was $2260.24 (pre-COVID) and $2,460.24 (post-COVID). The observed screening efficiency suggests that a well-resourced screening program can generate sufficient responder-derived donor material for clinical trial purposes. Eliminating testing for low-prevalence organisms may improve cost-effectiveness.

IMPORTANCE: High surgical vestibular schwannoma case volume in a medical institution may decrease the risk of adverse outcomes among patients undergoing vestibular schwannoma surgery. OBJECTIVE: To study the association between surgical vestibular schwannoma case volume and excess time in the hospital after vestibular schwannoma surgery. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated data from the National Cancer Database from January 1, 2004, through December 31, 2019, on Commission on Cancer–accredited facilities in the US. The hospital-based sample comprised adult patients aged 18 years or older with a vestibular schwannoma treated with surgery. EXPOSURES: Facility case volume, defined as the mean number of surgical vestibular schwannoma cases per year in the 2 years preceding the index case. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of prolonged hospital stay (>90th percentile) or 30-day readmission. Risk-adjusted restricted cubic splines were used to model the probability of the outcome according to facility volume. The inflection point (in cases per year) when the declining risk of excess time in the hospital began to plateau was selected as the threshold to define high- and low-volume facilities. Outcomes were compared among patients treated at high- and low-volume facilities, with mixed-effects logistic regression models adjusting for patient sociodemographic characteristics, comorbidities, tumor size, and clustering within facilities. Collected data were analyzed between June 24 and August 31, 2022. RESULTS: Among 11 524 eligible patients (mean [SD] age, 50.2 [12.8] years; 53.5% female; 46.5% male) who underwent surgical resection of vestibular schwannoma at 66 reporting facilities, the median length of stay was 4 (IQR, 3-5) days, and 655 patients (5.7%) were readmitted within 30 days. The median case volume was 16 (IQR, 9-26) cases per year. An adjusted restricted cubic spline model identified a downtrending probability of excess time in the hospital with increasing volume. The declining risk of excess time in the hospital began to plateau at a facility volume of 25 cases per year. Surgery at a facility with an annual case volume at or above this threshold was independently associated with a 42% reduction in the odds of excess time in the hospital compared with surgery at a low-volume center (odds ratio, 0.58; 95% CI, 0.44-0.77). CONCLUSIONS AND RELEVANCE: This cohort study found that among adults undergoing vestibular schwannoma surgery, a higher facility case volume was associated with a reduced risk of prolonged hospital stay or 30-day readmission. A facility case volume of 25 cases per year may represent a risk-defining threshold.

Tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) are approved CD19 CAR T products for adolescents and young adults (AYAs) with r/r B-ALL. These products have not previously been compared, yet overlap in age range presents a choice in therapy for AYAs. We describe real world efficacy and safety in AYAs with r/r B-ALL receiving tisa-cel or brexu-cel.

The central nervous system (CNS) respresents a common site of extramedullary disease relapse in acute lymphoblastic leukmeia (ALL). CNS relapses contribute to adverse outcomes, and frequently exclude patients from participating in clinical trials. Current approved novel salvage therapies (bliantumomab and inotuzumab) have limited activity in B-ALL with CNS relapse. Brexucabtagene autoleucel (brexu-cel) was the first FDA-approved CAR T-cell product for adult patients with relapsed/refractory (r/r) B-ALL based on the ZUMA-3 study, which excluded patients with clincally evident CNS involvement. The safety and efficacy of using brexu-cel in these patients is yet to be established.

In vivo T cell screens are a powerful tool for elucidating complex mechanisms of immunity, yet there is a lack of consensus on the screen design parameters required for robust in vivo screens: gene library size, cell transfer quantity, and number of mice. Here, we describe the Framework for In vivo T cell Screens (FITS) to provide experimental and analytical guidelines to determine optimal parameters for diverse in vivo contexts. As a proof-of-concept, we used FITS to optimize the parameters for a CD8+ T cell screen in the B16-OVA tumor model. We also included unique molecular identifiers (UMIs) in our screens to (1) improve statistical power and (2) track T cell clonal dynamics for distinct gene knockouts (KOs) across multiple tissues. These findings provide an experimental and analytical framework for performing in vivo screens in immune cells and illustrate a case study for in vivo T cell screens with UMIs.

The past several years have seen a significant increase in the number of mergers and acquisitions in Mexico. That trend should likely continue in the near future as many of [...]

The combination of venetoclax (ven) and azacitidine (aza) has resulted in high response rates in the upfront treatment of AML in patients age > 75 and patients unfit for intensive chemotherapy. Given the poor historical outcomes in patients age ≥ 60 treated with induction chemotherapy, ven/aza has become our institutional preference for the initial treatment of non-core binding factor (CBF) AML patients age ≥ 60. The benefit of allogeneic stem cell transplant (SCT) in patients who achieve response to ven/aza is uncertain. We report outcomes of SCT-eligible patients treated at our center. Between 1/2015 and 1/2020, 119 newly diagnosed non-CBF AML patients age ≥ 60 received ven/aza as initial therapy. 21 patients underwent SCT; 31 additional patients were potentially SCT eligible but deferred SCT. Overall survival (OS) was significantly greater among SCT patients (median survival not reached) versus potentially SCT eligible patients not undergoing SCT (median 518 days) (p= 0.01). Our data suggest that ven/aza followed by SCT in newly diagnosed AML patients older than ≥ 60 results in excellent outcomes and likely improves outcomes over maintenance therapy. Ongoing investigation will further refine the optimal timing of and selection of patients for SCT based on prognostic disease features and response assessments.

INTRODUCTION One likely reason for the relatively high level of foreign investment into Mexico is Mexico's active role in negotiating and implementing free trade agreements (FTAs) and double taxation agreements [...]

Venetoclax (ven) plus azacitidine (aza) is the standard of care for patients with newly diagnosed acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy (IC). Some patients who are IC candidates instead receive ven/aza. We retrospectively analyzed patients with newly diagnosed AML who received ven/aza (n = 143) or IC (n = 149) to compare outcomes, seek variables that could predict response to 1 therapy or the other, and ascertain whether treatment recommendations could be refined. The response rates were 76.9% for ven/aza and 70.5% for IC. The median overall survival (OS) was 884 days for IC compared with 483 days for ven/aza (P= .0020). A propensity-matched cohort was used to compare outcomes in the setting of equivalent baseline variables, and when matched for age, biological risk, and transplantation, the median OS was 705 days for IC compared with not reached for ven/aza (P= .0667). Variables that favored response to ven/aza over IC included older age, secondary AML, and RUNX1mutations. AML M5 favored response to IC over ven/aza. In the propensity-matched cohort analyzing OS, older age, adverse risk, and RUNX1mutations favored ven/aza over IC, whereas intermediate risk favored IC over ven/aza. In conclusion, patients receiving IC have improved OS compared with those receiving ven/aza. However, in a propensity-matched cohort of patients with equivalent baseline factors, there was a trend toward favorable OS for ven/aza. Specific variables, such as RUNX1mutations, reported here for the first time, can be identified that favor ven/aza or IC, helping to guide treatment decisions for patients who may be eligible candidates for either therapy.

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR-T) cell therapy approved for adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). How social determinants of health (SDoH) affect outcomes of adults receiving brexu-cel is unknown.

•Haplo-cord and dual cord stem cell transplants have comparable relapse-free and overall survival rates.•Haplo-cord transplants are associated with higher acute graft-versus-host disease and engraftment syndrome rates, but faster neutrophil engraftment and shorter initial hospitalizations.•Selection of haplo-cord versus dual cord transplants should take these factors into account for the benefit of the patient.

•InO-exposed patients with relapsed/refractory B-cell acute lymphoblastic leukemia have inferior outcomes after brexu-cel, particularly those who were nonresponders to InO.•The negative association is unrelated directly to InO per se; rather, it reflects selection of patients with intrinsically adverse-risk ALL.

Outcomes for older adults (defined here as ≥55-65 years old) with acute lymphoblastic leukemia (ALL) are poor, with long-term survival less than 20%. Pediatric chemotherapy regimens produce long-term cure rates of 80% to 90% in children and 60% to 70% in adolescents and young adults with Ph-negative ALL, however, tolerability of intensive chemotherapy becomes problematic with advanced age due to comorbidities and reduced tolerability of chemotherapy leading to high rates of treatment-related mortality. For older adults with Ph-positive ALL, BCR-ABL1-directed tyrosine kinase inhibitors in combination with corticosteroids or chemotherapy produce deep remissions with low treatment-related toxicity but optimal postremission therapy is not known. New therapeutic approaches for older adults with ALL involve integration of the novel targeted agents including monoclonal antibody-based therapy with blinatumomab and inotuzumab ozogamicin in the frontline. Ongoing studies will ideally define optimal combinations and sequencing of novel agents with or without chemotherapy, tyrosine kinase inhibitors, and/or corticosteroids to maximize efficacy while avoiding treatment-related death. Anti-CD19 chimeric antigen receptor modified T cells are a promising modality, with high rates of remission and minimal residual disease negativity achieved in early phase trials for adults with relapsed/refractory B-cell ALL but the tolerability of chimeric antigen receptor modified T cell therapies in older adults is yet to be well defined. Advances in minimal residual disease detection have helped to effectively stratify adults in complete response in terms of relapse risk and predicted relative benefit for allogeneic hematopoietic cell transplant. For older adults with ALL in complete response at high risk for relapse for whom myeloablative conditioning is predicted to result in excessive transplant-related mortality, reduced-intensity conditioning allogeneic hematopoietic cell transplant is a less toxic approach for providing a graft-versus-leukemia effect and long-term disease control.

Risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) are increasingly used to reduce breast and ovarian cancer risk following BRCA1/BRCA2 testing. However, little is known about how genetic counseling influences decisions about these surgeries. Although previous studies have examined intentions prior to counseling, few have examined RRM and RRSO intentions in the critical window between genetic counseling and test result disclosure. Previous research has indicated that intentions at this time point predict subsequent uptake of surgery, suggesting that much decision-making has taken place prior to result disclosure. This period may be a critical time to better understand the drivers of prophylactic surgery intentions. The aim of this study was to examine predictors of RRM and RRSO intentions. We hypothesized that variables from the Health Belief Model would predict intentions, and we also examined the role of affective factors. Participants were 187 women, age 21-75, who received genetic counseling for hereditary breast and ovarian cancer. We utilized multiple logistic regression to identify independent predictors of intentions. 49.2% and 61.3% of participants reported intentions for RRM and RRSO, respectively. Variables associated with RRM intentions include: newly diagnosed with breast cancer (OR = 3.63, 95% CI = 1.20-11.04), perceived breast cancer risk (OR = 1.46, 95% CI = 1.17-1.81), perceived pros (OR = 1.79, 95% CI = 1.38-2.32) and cons of RRM (OR = 0.81, 95% CI = 0.65-0.996), and decision conflict (OR = 0.80, 95% CI = 0.66-0.98). Variables associated with RRSO intentions include: proband status (OR = 0.28, 95% CI = 0.09-0.89), perceived pros (OR = 1.35, 95% CI = 1.11-1.63) and cons of RRSO (OR = 0.72, 95% CI = 0.59-0.89), and ambiguity aversion (OR = 0.79, 95% CI = 0.65-0.95). These data provide support for the role of genetic counseling in fostering informed decisions about risk management, and suggest that the role of uncertainty should be explored further.

Background:It remains unclear whether measurable residual disease (MRD) detected by next-generation sequencing (NGS) or BCR-ABL RT-PCR is more accurate in predicting relapse and guiding clinical management in patients with Ph+ acute lymphoblastic leukemia (ALL). In this multi-center retrospective study, we examine the discordance between BCR-ABL PCR and NGS MRD to better characterize practice patterns for disease monitoring for patients with Ph+ ALL.

Introduction:

Introduction:

INTRODUCTION

Introduction: Financial toxicity is the harmful effect of treatment costs on a patient's quality of life. Financial toxicity is common among cancer patients, and patients with hematologic malignancies often report worse financial toxicity than patients with other cancers. Thus, interventions to address financial toxicity in patients with hematologic cancers are urgently needed. Promising approaches include the use of digital media such as websites and educational videos. However, digital interventions may not be accessible for patients with low digital health literacy (DHL; the capacity to find and understand health-related information using electronic media). Information about DHL in patients with blood cancers is needed to inform future interventions addressing financial toxicity and other quality-of-life related issues. Here, we present a mixed-methods study describing DHL and its correlates among patients with non-Hodgkin lymphoma (NHL) who participated in a larger study about financial toxicity.

Background

Introduction: