Hildegard Greinix

The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic graft-versus-host disease (GVHD). The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence. Revisions have been made to address areas of controversy or confusion, such as the overlap chronic GVHD subcategory and the distinction between active disease and past tissue damage. Diagnostic criteria for involvement of mouth, eyes, genitalia, and lungs have been revised. Categories of chronic GVHD should be defined in ways that indicate prognosis, guide treatment, and define eligibility for clinical trials. Revisions have been made to focus attention on the causes of organ-specific abnormalities. Attribution of organ-specific abnormalities to chronic GVHD has been addressed. This paradigm shift provides greater specificity and more accurately measures the global burden of disease attributed to GVHD, and it will facilitate biomarker association studies.

BACKGROUND: Invasive fungal infections are an important cause of morbidity and mortality after allogeneic hematopoietic stem-cell transplantation. METHODS: In an international, randomized, double-blind trial, we compared oral posaconazole with oral fluconazole for prophylaxis against invasive fungal infections in patients with graft-versus-host disease (GVHD) who were receiving immunosuppressive therapy. The primary end point was the incidence of proven or probable invasive fungal infections from randomization to day 112 of the fixed treatment period of the study. RESULTS: Of a total of 600 patients, 301 were assigned to posaconazole and 299 to fluconazole. At the end of the fixed 112-day treatment period, posaconazole was found to be as effective as fluconazole in preventing all invasive fungal infections (incidence, 5.3% and 9.0%, respectively; odds ratio, 0.56; 95 percent confidence interval [CI], 0.30 to 1.07; P=0.07) and was superior to fluconazole in preventing proven or probable invasive aspergillosis (2.3% vs. 7.0%; odds ratio, 0.31; 95% CI, 0.13 to 0.75; P=0.006). While patients were receiving study medications (exposure period), in the posaconazole group, as compared with the fluconazole group, there were fewer breakthrough invasive fungal infections (2.4% vs. 7.6%, P=0.004), particularly invasive aspergillosis (1.0% vs. 5.9%, P=0.001). Overall mortality was similar in the two groups, but the number of deaths from invasive fungal infections was lower in the posaconazole group (1%, vs. 4% in the fluconazole group; P=0.046). The incidence of treatment-related adverse events was similar in the two groups (36% in the posaconazole group and 38% in the fluconazole group), and the rates of treatment-related serious adverse events were 13% and 10%, respectively. CONCLUSIONS: Posaconazole was similar to fluconazole for prophylaxis against fungal infections among patients with GVHD. It was superior in preventing invasive aspergillosis and reducing the rate of deaths related to fungal infections. (ClinicalTrials.gov number, NCT00034645 [ClinicalTrials.gov].).

In 2005, the National Institutes of Health (NIH) Chronic Graft-versus-Host Disease (GVHD) Consensus Response Criteria Working Group recommended several measures to document serial evaluations of chronic GVHD organ involvement. Provisional definitions of complete response, partial response, and progression were proposed for each organ and for overall outcome. Based on publications over the last 9 years, the 2014 Working Group has updated its recommendations for measures and interpretation of organ and overall responses. Major changes include elimination of several clinical parameters from the determination of response, updates to or addition of new organ scales to assess response, and the recognition that progression excludes minimal, clinically insignificant worsening that does not usually warrant a change in therapy. The response definitions have been revised to reflect these changes and are expected to enhance reliability and practical utility of these measures in clinical trials. Clarification is provided about response assessment after the addition of topical or organ-targeted treatment. Ancillary measures are strongly encouraged in clinical trials. Areas suggested for additional research include criteria to identify irreversible organ damage and validation of the modified response criteria, including in the pediatric population.

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.