Letermovir for prevention of recurrent CMV in high-risk allogeneic hematopoietic cell transplant (HCT) recipients.

Background: We evaluated letermovir (LTV) for secondary prophylaxis for cytomegalovirus (CMV) in allogeneic hematopoietic cell transplant recipients (HCT) at high-risk for CMV recurrence.

Methods: Open-label study conducted at Memorial Sloan Kettering Cancer Center and the University of Minnesota. Patients with clinically significant CMV infection (cs-CMVi) and ≥1 high-risk criteria for CMV who achieved viral suppression with standard CMV antivirals, received letermovir (LTV) secondary prophylaxis for up to 14 weeks.

Comparative Emergence of Maribavir and Ganciclovir Resistance in a Randomized Phase 3 Clinical Trial for Treatment of Cytomegalovirus Infection.

Background: Among 547 patients receiving maribavir or valganciclovir for first-episode cytomegalovirus infection after hematopoietic cell transplant, the treatment response rate was 69.6% and 77.4% respectively.

A randomized, placebo-controlled, dose-escalation phase I/II multicenter trial of low-dose cidofovir for BK polyomavirus nephropathy.

Background: BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV).

Methods: We report the results of a phase I/II, double-blind, placebo-controlled randomized dose-escalation trial of cidofovir in KTRs with biopsy-confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min.

Daily Fungal Cell-Free DNA Testing to Assess Clinical Status during Fungemia.

We present a case of a man immunocompromised due to myelodysplastic syndrome with fungemia who had a rising cell-free DNA (cfDNA) giant magnetoresistance (GMR) signal when tested daily using plasma blood samples. With the rise in GMR signal paralleling the development of skin lesions in this patient, we conclude that cfDNA can be used to indicate uncontrolled infection and thus help monitor response to therapy. This index patient provides evidence that an invasive fungal infection requires both direct antifungal therapy and an intact immune system to control the infection.

Diagnostic and prognostic significance of circulating secreted frizzled-related protein 5 in colorectal cancer.

Background: Secreted Frizzled-Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC) METHODS: Plasma cSFRP5 concentrations were measured using enzyme-linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64).

Results: Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p < 0.

SARS-CoV-2 Vaccination in the First Year After Hematopoietic Cell Transplant or Chimeric Antigen Receptor T-Cell Therapy: A Prospective, Multicenter, Observational Study.

Background: The optimal timing of vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines after cellular therapy is incompletely understood. The objectives of this study are to determine whether humoral and cellular responses after SARS-CoV-2 vaccination differ if initiated <4 months versus 4-12 months after cellular therapy.

Methods: We conducted a multicenter, prospective, observational study at 30 cancer centers in the United States.

Final outcomes from a phase 2 trial of posoleucel in allogeneic hematopoietic cell transplant recipients.

Allogeneic hematopoietic cell transplantation (allo-HCT) recipients are susceptible to viral infections. We conducted a phase 2 trial evaluating the safety and rate of clinically significant infections (CSIs; viremia requiring treatment or end-organ disease) after infusion of posoleucel, a partially HLA-matched, allogeneic, off-the-shelf, multivirus-specific T-cell investigational product for preventing CSIs with adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, or JC virus. This open-label trial enrolled allo-HCT recipients at high risk based on receiving grafts from umbilical cord blood, haploidentical, mismatched, or matched unrelated donors; post-HCT lymphocytes of <180/mm3; or use of T-cell depletion.

Modeling Invasive Aspergillosis Risk for the Application of Prophylaxis Strategies.

The epidemiology of invasive aspergillosis (IA) is evolving. To define the patient groups who will most likely benefit from primary or secondary prophylaxis, particularly those whose medical conditions and IA risk change over time, it is helpful to depict patient populations and their risk periods in a temporal visual model. The Sankey approach provides a dynamic figure to understand the risk of IA for various patient populations.

Posoleucel in Kidney Transplant Recipients with BK Viremia: Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

Key Points: Posoleucel was generally safe, well tolerated, and associated with a greater reduction of BK viremia compared with placebo. BK viremia reduction occurred coincident with an increase in the circulating frequency of BK virus–specific T cells in posoleucel recipients. The presence and persistence of posoleucel was confirmed by T-cell receptor variable sequencing.

Defining and Grading Infections in Clinical Trials Involving Hematopoietic Cell Transplantation: A Report From the BMT CTN Infectious Disease Technical Committee.

The Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) was established in 2001 to conduct large multi-institutional clinical trials addressing important issues towards improving the outcomes of HCT and other cellular therapies. Trials conducted by the network investigating new advances in HCT and cellular therapy not only assess efficacy but require careful capturing and severity assessment of adverse events and toxicities. Adverse infectious events in cancer clinical trials are typically graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE).

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101).

Background: The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood.

Objective: To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy.

Design: Multicenter prospective observational study.

A multicenter prospective study to define the natural history of BK viral infections in kidney transplantation.

Background: BK polyomavirus (BKV) can cause permanent loss of allograft function due to BKV-associated nephropathy (BKVN) in kidney transplant recipients. Besides immunosuppression reduction, there are no consistently effective interventions for BKV infection. Study purpose was to define natural history of BKV infection, identify risk factors for BKV reactivation and BKVN in kidney transplant recipients, and inform the design/conduct of future clinical trials of BKV-targeted therapeutics.

Treatment for First Cytomegalovirus Infection Post-Hematopoietic Cell Transplant in the AURORA Trial: A Multicenter, Double-Blind, Randomized, Phase 3 Trial Comparing Maribavir With Valganciclovir.

Background: Neutropenia may limit the use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of maribavir with fewer treatment-limiting toxicities than valganciclovir.

Methods: In this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 1:1 to maribavir 400 mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks of follow-up.

Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis.

Unlabelled: Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes.

Age-Specific Differences in the Risk of Colorectal Precursor Lesions Among Patients with Type 2 Diabetes Undergoing Surveillance Colonoscopy.

Background: The incidence rate of colorectal cancer (CRC) in young adults is rising in parallel with type 2 diabetes (T2D). The majority of CRC develop through two main subtypes of precursor lesions; adenomas and serrated lesions. The associations between age and T2D on development of precursor lesions remain uncertain.

SARS-CoV-2 vaccination in the first year after allogeneic hematopoietic cell transplant: a prospective, multicentre, observational study.

Background: The optimal timing for SARS-CoV-2 vaccines within the first year after allogeneic hematopoietic cell transplant (HCT) is poorly understood.

Methods: We conducted a prospective, multicentre, observational study of allogeneic HCT recipients who initiated SARS-CoV-2 vaccinations within 12 months of HCT. Participants were enrolled at 22 academic cancer centers across the United States.

Chronic GVHD after steroid-sensitive, -dependent, and -refractory acute GVHD: incidence and clinical outcomes.

Chronic graft-versus-host disease (cGVHD) is a major limitation to the long-term success of allogeneic hematopoietic cell transplantation (HCT). Our prior study of acute GVHD (aGVHD) defined distinct treatment-response groups based on the response to first-line corticosteroids: steroid-sensitive (SS), steroid-resistant (SR), and steroid-dependent (SD) aGVHDs. We conducted a retrospective, single-institution, cohort study to assess the incidence, risk factors, and clinical outcomes of patients with cGVHD after a previous diagnosis of SS, SD, or SR aGVHD, compared with those with no history of aGVHD.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant.

Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation.

Young-Onset Gastrointestinal Adenocarcinoma Incidence and Survival Trends in the Northern Territory, Australia, with Emphasis on Indigenous Peoples.

Background and Aims: A concerning rise in incidence of young-onset cancers globally led to the examination of trends in incidence and survival of gastrointestinal (GI) adenocarcinomas in the Northern Territory (NT), Australia, over a 28-year period, with a special emphasis on Indigenous peoples. Methods: This cross-sectional analysis of a prospective longitudinal database, NT Cancer Registry (1990−2017), includes all reported cases of GI (oesophagus, gastric, small intestinal, pancreas, colon, and rectum) adenocarcinomas. Poisson regression was used to estimate incidence ratio ratios, and survival was modelled using Cox proportional hazard models separately for people aged 18−50 years and >50 years.

Steroid-Sensitive, but Not Steroid-Dependent or Steroid-Resistant Acute Graft-versus-Host Disease, Results in Similar Infection Risk as No Graft-versus-Host Disease following Allogeneic Hematopoietic Cell Transplantation.

Patients with acute graft-versus-host disease (GVHD) have an increased risk for infectious complications after allogeneic hematopoietic cell transplantation (HCT), but the risk according to response to therapy has not been well studied. We performed a retrospective analysis of the infectious complications for 1 year following allogeneic HCT at the University of Minnesota including 1143 pediatric and adult patients with and without aGVHD. The patients with aGVHD were classified into treatment response groups based on response to corticosteroids as first-line therapy: steroid-sensitive (SS; n = 114), steroid-resistant (SR; n = 103), and steroid-dependent (SD; n = 168) aGVHD.

Reduced Enterohepatic Recirculation of Mycophenolate and Lower Blood Concentrations Are Associated with the Stool Bacterial Microbiome after Hematopoietic Cell Transplantation.

Mycophenolate mofetil (MMF) is an important immunosuppressant used after allogeneic hematopoietic cell transplantation (HCT). MMF has a narrow therapeutic index, and blood concentrations of mycophenolic acid (MPA), the active component of MMF, are highly variable. Low MPA concentrations are associated with the risk of graft-versus-host disease (GVHD), whereas high concentrations are associated with toxicity.

Pharmacist-Facilitated Interactive E-Learning for Patients Newly Initiated on Warfarin: A Randomised Controlled Study.

It is not known whether electronic-learning (e-learning) is effective for educating hospital inpatients about complex medications such as warfarin. This prospective randomised controlled study compared pharmacist-facilitated e-learning with standard pharmacist-delivered face-to-face education on patients' or their unpaid carers' knowledge of warfarin and satisfaction with warfarin education as well as the time that was spent by pharmacists in delivering warfarin education. Adult English-speaking patients (or their carers) who had been prescribed warfarin were randomised to receive standard pharmacist face-to-face education (control) or an e-learning module on a tablet device facilitated by a pharmacist (intervention).

Systemic antifungal therapy with isavuconazonium sulfate or other agents in adults with invasive mucormycosis or invasive aspergillosis (non-fumigatus): A multicentre, non-interventional registry study.

Background: Isavuconazole, administered as isavuconazonium sulfate (ISAVUSULF), is a broad-spectrum triazole agent for the treatment of invasive fungal disease. In phase 3 studies, ISAVUSULF showed comparable efficacy to voriconazole and amphotericin B for the treatment of invasive aspergillosis (IA) and invasive mucormycosis (IM), respectively.

Objectives: The objective of this study is to determine all-cause mortality and safety outcomes among adults with IM and/or IA non-fumigatus (nf) treated with ISAVUSULF or other antifungal therapies (AFT).