Chronic graft versus host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Clinically, chronic GVHD is a pleiotropic, multiorgan ...syndrome involving tissue inflammation and fibrosis that often results in permanent organ dysfunction. Chronic GVHD is fundamentally caused by replacement of the host's immune system with donor cells, although the heterogeneity of clinical manifestations suggests that patient, donor, and transplant factors modulate the phenotype. The diagnosis of chronic GVHD and determination of treatment response largely rely on clinical examination and patient interview. The 2005 and 2014 National Institutes of Health Consensus Development Projects on Criteria for Clinical Trials in Chronic GVHD standardized the terminology around chronic GVHD classification systems to ensure that a common language and procedures are being used in clinical research. This review provides a summary of these recommendations and illustrates how they are being used in clinical research and the potential for their use in clinical care.
Racial and ethnic disparities in patients with solid malignancies have been well documented. Less is known about these disparities in patients with hematologic malignancies. With the advent of novel ...chemotherapeutics and targeted molecular, cellular, and immunologic therapies, it is important to identify differences in care that may lead to disparate outcomes. This review provides a critical appraisal of the empirical research on racial and ethnic disparities in incidence, survival, and outcomes in patients with hematologic malignancies. The review focuses on patients with acute myeloid leukemia, acute lymphocytic leukemia, multiple myeloma, non-Hodgkin lymphoma, Hodgkin lymphoma, myeloproliferative neoplasms, and myelodysplastic syndrome. The review discusses possible causes of racial and ethnic disparities and also considers future directions for studies to help decrease disparities.
Chronic graft-versus-host disease (cGVHD) is a major immunologic complication of allogeneic hematopoietic cell transplantation. cGVHD involves multiple organs, reduces quality of life, and often ...requires prolonged therapy with glucocorticoids, causing severe side effects. After 4 decades of testing multiple therapeutic approaches, ibrutinib, belumosudil, and ruxolitinib were US Food and Drug Administration approved for cGVHD in the last 4 years. Here we put a spotlight on their mechanisms of action, studies that led to approval, and their future role in cGVHD.
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Hematopoietic cell transplantation is a curative treatment for a variety of hematologic diseases. Advances in transplantation technology have reduced early transplant-related mortality and expanded ...application of transplantation to older patients and to a wider variety of diseases. Management of late effects after transplantation is increasingly important for a growing number of long-term survivors that is estimated to be half a million worldwide. Many studies have shown that transplant survivors suffer from significant late effects that adversely affect morbidity, mortality, working status and quality of life. Late effects include diseases of the cardiovascular, pulmonary, and endocrine systems, dysfunction of the thyroid gland, gonads, liver and kidneys, infertility, iron overload, bone diseases, infection, solid cancer, and neuropsychological effects. The leading causes of late mortality include recurrent malignancy, lung diseases, infection, secondary cancers and chronic graft-
-host disease. The aim of this review is to facilitate better care of adult transplant survivors by summarizing accumulated evidence, new insights, and practical information about individual late effects. Further research is needed to understand the biology of late effects allowing better prevention and treatment strategies to be developed.
The amyloid beta-protein (Abeta) is believed to be the key mediator of Alzheimer's disease (AD) pathology. Abeta is most often characterized as an incidental catabolic byproduct that lacks a normal ...physiological role. However, Abeta has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities.
Here, we provide data supporting an in vivo function for Abeta as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of Abeta and LL-37, an archetypical human AMP. Findings reveal that Abeta exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue Abeta levels. Consistent with Abeta-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-Abeta antibodies.
Our findings suggest Abeta is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of Abeta-mediated pathology and has important implications for ongoing and future AD treatment strategies.
Standard treatment for GVHD is glucocorticoids, but for glucocorticoid-refractory GVHD, no intervention has emerged as standard second-line treatment. This trial with 329 patients compared ...ruxolitinib with control (chosen from among 10 possible therapies) in patients with glucocorticoid-refractory chronic GVHD. Response at week 24 was 50% with ruxolitinib as compared with 26% with control therapy.
The impacts of COVID-19 on workers and workplaces across the globe have been dramatic. This broad review of prior research rooted in work and organizational psychology, and related fields, is ...intended to make sense of the implications for employees, teams, and work organizations. This review and preview of relevant literatures focuses on (a) emergent changes in work practices (e.g., working from home, virtual teamwork) and (b) emergent changes for workers (e.g., social distancing, stress, and unemployment). In addition, potential moderating factors (demographic characteristics, individual differences, and organizational norms) are examined given the likelihood that COVID-19 will generate disparate effects. This broad-scope overview provides an integrative approach for considering the implications of COVID-19 for work, workers, and organizations while also identifying issues for future research and insights to inform solutions.
Public Significance Statement
COVID-19 has disrupted work and organizations across the globe. This overview integrates and applies prior research in work and organizational psychology as well as related fields in its examination of emergent changes for work practices as well as workers. This article also acknowledges and considers the disproportionate impacts that COVID-19 may have on workers depending on demographic characteristics, individual differences, and relevant organizational norms. In addition to helping make sense of the implications of COVID-19 for employees, teams, and work organizations, this review features roadmaps for future research and action.
In this issue of
Blood
,
Zhang et al
report that the WNT signaling pathway is involved in human and mouse sclerotic chronic graft-versus-host disease (cGVHD) and can be blocked by available ...inhibitors, providing support for targeting this pathway therapeutically.
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Allogeneic hematopoietic cell transplantation is indicated for refractory hematologic cancer and some nonmalignant disorders. Survival is limited by recurrent cancer and organ toxicity.
To determine ...whether survival has improved over the past decade and note impediments to better outcomes.
The authors compared cohorts that had transplants during 2003 to 2007 versus 2013 to 2017. Survival outcome measures were analyzed, along with transplant-related complications.
A center performing allogeneic transplant procedures.
All recipients of a first allogeneic transplant during 2003 to 2007 and 2013 to 2017.
Patients received a conditioning regimen, infusion of donor hematopoietic cells, then immunosuppressive drugs and antimicrobial approaches to infection control.
Day-200 nonrelapse mortality (NRM), recurrence or progression of cancer, relapse-related mortality, and overall mortality, adjusted for comorbidity scores, source of donor cells, donor type, patient age, disease severity, conditioning regimen, patient and donor sex, and cytomegalovirus serostatus.
During the 2003-to-2007 and 2013-to-2017 periods, 1148 and 1131 patients, respectively, received their first transplant. Over the decade, decreases were seen in the adjusted hazards of day-200 NRM (hazard ratio HR, 0.66 95% CI, 0.48 to 0.89), relapse of cancer (HR, 0.76 CI, 0.61 to 0.94), relapse-related mortality (HR, 0.69 CI, 0.54 to 0.87), and overall mortality (HR, 0.66 CI, 0.56 to 0.78). The degree of reduction in overall mortality was similar for patients who received myeloablative versus reduced-intensity conditioning, as well as for patients whose allograft came from a matched sibling versus an unrelated donor. Reductions were also seen in the frequency of jaundice, renal insufficiency, mechanical ventilation, high-level cytomegalovirus viremia, gram-negative bacteremia, invasive mold infection, acute and chronic graft-versus-host disease, and prednisone exposure.
Cohort studies cannot determine causality, and current disease severity criteria were not available for patients in the 2003-to-2007 cohort.
Improvement in survival and reduction in complications were substantial after allogeneic transplant. Relapse of cancer remains the largest obstacle to better survival outcomes.
National Institutes of Health.
Several international recommendations address the assessment of graft-versus-host disease (GvHD) after hematopoietic cell transplantation (HCT). This position statement by GvHD experts from the ...European Society for Blood and Marrow Transplantation (EBMT), the National Institutes of Health (NIH) and the Center for International Blood and Marrow Transplant Research (CIBMTR) reviews the existing guidelines for both acute and chronic GvHD, addresses potential confusions that arise in daily practice and proposes consensus definitions for many key terms. We provide a historical perspective on the currently available guidelines and recommend the Mount Sinai Acute GvHD International Consortium (MAGIC) criteria for acute GvHD and the NIH 2014 criteria for chronic GvHD as the most comprehensive and detailed criteria available. This statement also offers practical guidance for the implementation of these recommendations and a set of consensus definitions for commonly used GvHD terms in order to facilitate future clinical and translational research. To assist the dissemination of these recommendations, a web-application based on this position statement is available ( https://www.uzleuven.be/egvhd ). We believe that adherence to a common set of GvHD assessment criteria is vitally important to improve the quality of data, compare results of retrospective studies and prospective clinical trials, and make therapeutic recommendations based on quality evidence.
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