Accurately diagnosing and scoring acute and chronic graft-versus-host disease (GvHD) remain challenging for many hematologists. Inconsistency between bone marrow transplant centers has been recognized in this field, in particular because of problems in following the latest recommended guidelines.31 In this regard, Schoemans et al. present a new electronic tool, the eGVHD application (eGVHD App), designed to improve and harmonize GvHD assessment.4
The eGVHD app was developed by the UZ Leuven (Belgium) in collaboration with the European Society for Blood and Marrow Transplantation (EBMT) Transplantation Complications Working Party and the National Institute of Health (NIH) (Bethesda, USA). This e-tool is a free, open-source web application, distributed as a normal website or a mobile application (accessible at: www.uzleuven.be/egvhd). The App allows the diagnosis of classic and late acute, as well as classic and overlap chronic GvHD, using the most up-to date guidelines [Mount Sinai Acute GvHD International Consortium (MAGIC) for acute and NIH 2014 for chronic GvHD].
The study presented in this issue of the Journal4 was performed in 7 Belgian centers practising allogeneic hematopoietic stem cell transplantation (HSCT) and included 77 health care practitioners (HPCs), among whom 58 were physicians (75%), 15 were data managers (19%), and 4 held another position. They were invited to evaluate the diagnosis and severity score of 10 clinical vignettes (4 acute and 6 chronic GvHD) validated by a group of 10 separate GvHD experts (Expert Gold Standard) who implemented the latest guidelines. For their evaluation, the 77 HCPs were randomized to either use their usual GvHD assessment tools without the eGVHD App (No App group, n=40) or to use the eGVHD App (App group, n=37) (Figure 1).
The most frequently reported GvHD guidelines referenced by HPCs in the No App group were the Glucksberg5 and the NIH 20146 criteria. They assessed GvHD of the 10 case vignettes mostly by their own knowledge (62%) or by using the 2014 GvHD evaluation sheet (23%), the 2005 NIH evaluation sheet (15%), or a self-designed scoring document (15%). The use of the App compared to the No App group improved the number of vignettes with a correct diagnosis [10/10 vs. 6.5/10, respectively; OR=6.14 (95%CI: 2.83–13.34; P<0.001)] as well as the number of vignettes with correct GvHD scoring [9/10 vs. 4.5/10, respectively; OR=6.29 (95%CI: 4.32–9.15; P<0.001)]. Assessment of GvHD was significantly better in the App group for both acute (aGvHD) (OR=17.89; 95%CI: 8.47–37.79; P<0.001) and chronic (cGvHD) (OR=4.34; 95%CI: 2.79–6.74; P<0.001) GvHD. As shown in Figure 1, agreement between the HPCs’ results and the Expert Gold Standard evaluations also showed the superiority of the use of the eGVHD App. For GvHD diagnosis, the No App group more often misdiagnosed late acute and overlap chronic GvHD by considering them as classic cGvHD. Scoring of aGvHD was frequently false in the No App group, in particular for grades II and IV, confused with cGvHD and grade III aGvHD, respectively. Scoring for cGvHD tended to be over-estimated (15%) or under-estimated (9%) by the App group without misclassification, while both diagnosis and scoring were frequently erroneous in the No App group.
Agreement between HPCs was superior in the App group (0.73 vs. 0.56 in the No App group) independently of the center, the degree of experience, and professional background. The use of the App was, however, time consuming for the HCPs who had not used it before the study. Despite this limiting factor, they found it useful and reported that they would be willing to use it in their daily practice.
Thus, this well-performed randomized study demonstrates that the eGVHD App provides superior accuracy and reliability for GvHD assessment compared to usual care, even for experienced physicians.4 The improvement can mainly be explained by the use of the most up-to-date guidelines, the limitation of physician’s subjectivity during the evaluation, and the fact that the e-tool provides pictures and definitions of GvHD features that help physicians to better categorize GvHD symptoms.
The need for harmonization in the diagnosis and scoring of GvHD has been recognized for many years and several other attempts have been made to improve this by the use of electronic tools87 but generally without success. The eGVHD App is available everywhere (www.uzleuven.be/egvhd) and could be used by any practitioner. The App could be of particular interest to HPCs with limited GvHD experience and can also be used for training. It remains to be seen whether the use of the eGVHD App, by improving the grading of GvHD in daily practice, could have an impact on clinical decisions and transplant outcomes.
In the era of fast developing electronic devices and of ‘big-data’ analyses, the eGVHD App represents the first e-tool to be made widely available with the potential to improve the quality of GvHD data in clinical research. Such an App should be implemented in clinical trials aiming to evaluate and treat GvHD after allogeneic HSCT, as well as in large-scale transplant data bases.
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