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"Carpenter, Paul"
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Whose Middle Ages? : teachable moments for an ill-used past
\"Whose Middle Ages? is an interdisciplinary collection of short, accessible essays intended for the nonspecialist reader and ideal for teaching at an undergraduate level. Each of twenty-two essays takes up an area where digging for meaning in the medieval past has brought something distorted back into the present: in our popular entertainment; in our news, our politics, and our propaganda; and in subtler ways that inform how we think about our histories, our countries, and ourselves. Each author looks to a history that has refused to remain past and uses the tools of the academy to read and re-read familiar stories, objects, symbols, and myths\"-- Provided by publisher.
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Study protocol: Close Assessment and Testing for Chronic Graft-vs.-Host disease (CATCH)
Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that causes significant late morbidity and mortality following allogeneic hematopoietic cell transplantation. The “Close Assessment and Testing for Chronic GVHD (CATCH)” study is a multi-center Chronic GVHD Consortium prospective, longitudinal cohort study designed to enroll patients before hematopoietic cell transplantation and follow them closely to capture the development of chronic GVHD and to identify clinical and biologic biomarkers of chronic GVHD onset. Data are collected pre-transplant and every two months through one-year post-transplant with chart review thereafter. Evaluations include clinician assessment of chronic GVHD and its manifestations, patient-reported outcomes, multiple biospecimens (blood, saliva, tears, buccal mucosa and fecal samples, biopsies of skin and mouth), laboratory testing, and medical record abstraction. This report describes the rationale, design, and methods of the CATCH study, and invites collaboration with other investigators to leverage this resource. trial registration : This study is registered at www.clinicaltrials.gov as NCT04188912 .
Journal Article
Novel factors to predict respiratory viral disease progression in allogeneic hematopoietic cell transplant recipients
We assessed novel factors and the immunodeficiency scoring index (ISI) to predict progression to lower respiratory tract infection (LRTI) among hematopoietic cell transplant (HCT) recipients presenting with upper respiratory tract infection (URTI) with 12 viruses in the PCR era. We retrospectively analyzed the first respiratory virus detected by multiplex PCR in allogeneic HCT recipients (4/2008–9/2018). We used Cox proportional hazards models to examine factors for progression to LRTI within 90 days among patients presenting with URTI. A total of 1027 patients (216 children and 811 adults) presented with URTI only. Among these, 189 (18%) progressed to LRTI (median: 12 days). Multivariable models demonstrated a history of >1 transplant, age ≥40 years, time post-HCT (≤30 days), systemic steroids, hypoalbuminemia, hyperglycemia, cytopenia, and high ISI (scores 7–12) were associated with an increased risk of progression to LRTI. Respiratory syncytial virus and human metapneumovirus showed the highest progression risk. Patients with ≥3 independent risk factors or high ISI scores were highly likely to progress to LRTI. We identified novel risk factors for progression to LRTI, including history of multiple transplants and hyperglycemia, suggesting an intervention opportunity with glycemic control. ISI and number of risk factors appear to predict disease progression across several viruses.
Journal Article
Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the EBMT, ASTCT, CIBMTR, and APBMT
Despite emergence of novel therapies to treat hematologic malignancies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an essential treatment modality capable of curing these diseases. Allo-HCT has been also shown to be curative in benign hematologic disorders such as aplastic anemia, sickle cell disease, and thalassemia, among others. Recently, the American Society for Transplantation and Cellular Therapy (ASTCT) published standardized definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism. To attempt broader international consensus, a panel of adult and pediatric physician transplant experts was assembled from European Society for Blood and Marrow Transplantation (EBMT), ASTCT, the Center for International Blood and Marrow Transplant Research (CIBMTR), and Asia-Pacific Blood and Marrow Transplantation (APBMT). Consensus was defined as ≥70% of voting members strongly agreeing or somewhat agreeing with a definition. With few exceptions, there was a consensus to endorse the prior ASTCT definitions. Importantly, we revised existing EBMT and CIBMTR data collection forms to align with these harmonized definitions that will facilitate research and international collaboration among transplant researchers and across transplant registries.
Journal Article
Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)–an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)
On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.
Journal Article
Invasive Aspergillosis following Hematopoietic Cell Transplantation: Outcomes and Prognostic Factors Associated with Mortality
Background. Invasive aspergillosis (IA) is a leading cause of infection-related mortality following hematopoietic cell transplantation (HCT). The aim of this study was to determine the probability of survival and prognostic factors associated with outcomes over a long period of time. Methods. Cases of proven and probable IA diagnosed in HCT recipients at the Fred Hutchinson Cancer Research Center from 1 January 1990 through 31 December 2004 were included. Patient data were collected from a prospectively maintained database and by retrospective clinical chart review. Survival was estimated using Kaplan-Meier curves, and Cox regression models were used for multivariable analyses. Results. Four hundred five cases were identified. The probability of survival at 90 days after diagnosis was higher for patients identified as having IA between 2002 and 2004 than for patients whose IA was diagnosed in preceding years (45% vs. 22%; P < .001). Risk factors independently associated with all-cause mortality include impairment in pulmonary function before HCT, receipt of human leukocyte antigen—mismatched stem cells, neutropenia, elevated bilirubin and creatinine levels, receipt of corticosteroids at ≥2 mg/kg per day, disseminated and proven IA, and IA occurring>40 days after HCT. Factors associated with a decreased risk of all-cause mortality included receipt of nonmyeloablative conditioning and peripheral blood stem cells. In a subanalysis of attributable mortality restricted to patients receiving antifungal therapy, receipt of voriconazole was independently associated with protection from IA-related death. Conclusions. There has been a significant decrease in mortality in patients with a diagnosis of IA following HCT in recent years, coinciding with multiple changes in transplantation practices, including use of nonmyeloablative conditioning regimens, receipt of peripheral blood stem cells, more prompt diagnosis of IA, and use of voriconazole.
Journal Article
Vaccine hesitancy and routine revaccination among adult HCT survivors in the United States: A convergent mixed methods analysis
Revaccination to restore immunity to vaccine-preventable diseases (VPDs) is essential risk mitigation in the prevention of infectious morbidity and mortality after hematopoietic cell transplantation (HCT). However, revaccination rates have been shown to be insufficient and to what extent vaccine hesitancy contributes to survivors not becoming fully revaccinated is unknown. We performed a cross-sectional, mixed methods survey-based study to explore how vaccine hesitancy influences revaccination among US adult HCT survivors who were 2 to 8 years after transplant. Participants were asked to complete the Vaccination Confidence Scale (VCS) and open-ended survey items regarding vaccine confidence. The survey response rate was 30 %; among 332 respondents, vaccine confidence was high in 69 %, medium in 20 %, and low in 11 %. On multivariable analysis, four factors associated with high vaccine confidence were: predominantly Democrat zip codes (per 2020 election results), ability to pay for revaccination out of pocket, receipt of pre-HCT adult vaccines, and receipt of COVID-19 vaccines. From 189 participants who also answered open-ended items, 14 themes associated with vaccine confidence were identified and collapsed into 4 categories based on the VCS: Benefits, Harms, Trust, and Other. Merged analysis showed congruence between VCS scores and open-ended survey responses and created a narrative about the relative importance of the constructs when approaching revaccination by vaccine confidence level. These findings significantly expand our knowledge of how vaccine hesitancy influences revaccination uptake among US adult HCT survivors. Population-specific interventions to approach vaccine-hesitant survivors should be developed and tested.
Journal Article
Return to school practices after hematopoietic cell transplantation: a survey of transplant centers in the United States
To understand transplant center recommendations on return-to-school timing and related support for hematopoietic cell transplant (HCT) survivors, we conducted a two-phase, cross-sectional, web-based survey: In Phase I, medical directors of pediatric HCT centers from the National Marrow Donor Program/ Be The Match Registry were asked regarding the availability of a return to school standardized operating procedure (SOP). In Phase II, HCT physician members of the Pediatric Transplantation and Cellular Therapy Consortium were approached to study inter-physician practice variability regarding return to school post-HCT, factors affecting their decision-making, and support provided by HCT centers for return to school. Out of 46 respondents in Phase I (55% response rate), 28 (61%) reported having a SOP. Wide variations in recommendations were noted in 12 received SOPs. In Phase II, 122 physicians (60 centers) responded (30.6% response rate). The majority (60%) recommended autologous HCT recipients return to school within 6 months post-HCT but 65% recommended allogeneic HCT recipients return to school after 6 months or once off immunosuppression. Our findings indicate a lack of consensus within and across HCT centers regarding recommended return to school timing and underscore need for a guideline to standardize this process to ensure patient safety and re-integration into school.
Journal Article
Influenza Vaccine in Pediatric Recipients of Hematopoietic-Cell Transplants
In this trial involving children who had received a hematopoietic-cell transplant, a high-dose trivalent influenza vaccine elicited higher titers to influenza A antigens than a quadrivalent influenza vaccine.
Journal Article