Graft-versus-host disease (GVHD) is the major cause of non-relapse mortality after allogeneic haemopoietic stem-cell transplantation (SCT). The severity of symptoms at the onset of GVHD does not ...accurately define risk, and thus most patients are treated alike with high dose systemic corticosteroids. We aimed to define clinically meaningful risk strata for patients with newly diagnosed acute GVHD using plasma biomarkers.
Between April 13, 2000, and May 7, 2013, we prospectively collected plasma from 492 SCT patients with newly diagnosed acute GVHD and randomly assigned (2:1) using a random number generator, conditional on the final two datasets having the same median day of onset, into training (n=328) and test (n=164) sets. We used the concentrations of three recently validated biomarkers (TNFR1, ST2, and Reg3α) to create an algorithm that computed the probability of non-relapse mortality 6 months after GVHD onset for individual patients in the training set alone. We rank ordered the probabilities and identified thresholds that created three distinct non-relapse mortality scores. We evaluated the algorithm in the test set, and again in an independent validation set of an additional 300 patients who underwent stem cell transplant and were enrolled on multicentre clinical trials of primary therapy for acute GVHD.
In all three datasets (training, test, and validation), the cumulative incidence of 6-month non-relapse mortality significantly increased as the Ann Arbor GVHD score increased. In the multicentre validation set, scores were 8% (95% CI 3-16) for score 1, 27% (20-34) for score 2, and 46% (33-58) for score 3 (p<0·0001). Conversely, the response to primary GVHD treatment within 28 days decreased as the GVHD score increased 86% for score 1, 67% for score 2, and 46% for score 3 in the multicentre validation set, p<0·0001).
Biomarker-based scores can be used to guide risk-adapted therapy at the onset of acute GVHD. High risk patients with a score of 3 are candidates for intensive primary therapy, while low risk patients with a score of 1 are candidates for rapid tapers of systemic steroid therapy.
The National Cancer Institute, the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Doris Duke Charitable Fund, the American Cancer Society, and the Judith Devries Fund.
Abstract Objectives To evaluate the impact of oral health status on bacteremia risk in a cohort of acute myeloid leukemia (AML) patients who underwent chemotherapy followed by myeloablative ...allogeneic hematopoietic cell transplantation (alloHCT). Materials and Methods A retrospective study was conducted in patients with AML from 2007 to 2011. Oral health status was determined from a pre-alloHCT dental evaluation. Positive blood cultures were recorded from AML induction to day +60 post alloHCT. Organisms that caused bacteremia were classified as “of possible oral source” by a blinded microbiologist. Two-sided Fisher’s exact test was used to compare the oral health status of the entire cohort to patients with blood cultures of potential oral source. Results Pre-alloHCT dental evaluations were completed in 91/92 (99%) of patients. Of the 13/91 (14%) patients with dental pathology, 13/13 (100%) completed all required dental treatment prior to alloHCT. Bacteremias occurred in 63/92 (68%) patients, and 12/63 (19%) had positive blood cultures of potential oral source. Of these, 1/12 patient developed bacteremia during AML induction and 11/12 patients developed bacteremia during alloHCT. Conclusion Oral health status was not associated with risk of bacteremia of potential oral source at either AML induction/consolidation or alloHCT.
Current and novel therapies in acute GVHD Ho, Vincent T., MD; Cutler, Corey, MD, MPH, FRCP(C)
Best practice & research. Clinical haematology,
06/2008, Letnik:
21, Številka:
2
Journal Article
Recenzirano
Despite improvements in our understanding of transplant immunology and clinical and supportive care, acute graft-versus-host disease (GVHD) remains a clinical challenge and a major cause of morbidity ...and mortality for patients after allogeneic hematopoietic stem-cell transplantation. While systemic corticosteroid is standard primary therapy for acute GVHD, there is no established standard treatment in the steroid-refractory setting. New generations of monoclonal antibodies, biologics, and chemotherapeutics with immunomodulatory effects have been developed over the past decade, and are being tested as novel therapies in this disease. Many of these agents – including, among others, mycophenolate mofetil, anti-tumor necrosis factor-α antibodies, denileukin diftitox, and anti-interleukin-2Rα-chain antibodies – have demonstrated promising activity in steroid-refractory acute GVHD. Despite the high response rates, however, long-term survival remains poor due to a high incidence of infections. The key to improving acute GVHD outcomes may, in fact, rest upon successful initial therapy, and timely taper of corticosteroids to promote healthier immune reconstitution. Clinical trials combining these newer agents with systemic corticosteroids as initial treatment are under way, and will determine whether fortifying initial therapy will indeed reduce the development of steroid-refractory GVHD and improve long-term outcomes. In this article, we review current and novel agents available for acute GVHD, and discuss newer investigational approaches – such as phototherapy and cellular therapies – in the management of this common transplant complication.
Imaging is valuable in determining the presence, extent, and severity of myocardial ischemia and the severity of obstructive coronary lesions in patients with chronic chest pain in the setting of ...high probability of coronary artery disease. Imaging is critical for defining patients best suited for medical therapy or intervention, and findings can be used to predict long-term prognosis and the likely benefit from various therapeutic options. Chest radiography, radionuclide single photon-emission CT, radionuclide ventriculography, and conventional coronary angiography are the imaging modalities historically used in evaluating suspected chronic myocardial ischemia. Stress echocardiography, PET, cardiac MRI, and multidetector cardiac CT have all been more recently shown to be valuable in the evaluation of ischemic heart disease. Other imaging techniques may be helpful in those patients who do not present with signs classic for angina pectoris or in those patients who do not respond as expected to standard management. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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