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Stem Cell Transplantation
Validation of Minnesota acute graft-versus-host disease Risk Score
Margaret L. MacMillan,1,2 Todd E. DeFor,1,3 Shernan G. Holtan,1,4 Armin Rashidi,1,4 Bruce R. Blazar1,2 and Daniel J. Weisdorf1,4
1Blood and Marrow Transplant Program, University of Minnesota Medical School, Minneapolis, MN; 2Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN; 3Biostatistics and Informatics Core, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN and 4Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
ABSTRACT
Using multicenter data, we developed a novel acute graft-versus-host disease Risk Score which more accurately predicts response to steroid treatment, survival and transplant related mortality than other published risk scores based upon clinical grading criteria.1 To validate this Risk Score in a contemporary cohort, we examined 355 recent University of Minnesota patients (2007-2016) diagnosed with acute graft- versus-host disease and treated with prednisone 60 mg/m2/day for 14 days, followed by an 8-week taper. Overall response [complete response + partial response] was higher in the 276 standard risk versus 79 high risk graft-ver- sus-host disease patients at day 14 (71% versus 56%, P<0.01), day 28 (74% versus 59%, P=0.02) and day 56 (68% versus 49%, P<0.01) after steroid ini- tiation. Day 28 response did not differ by the initial graft-versus-host disease grade. In multiple regression analysis, patients with high risk graft-versus- host disease were less likely to respond at day 28 (odds ratio 0.5, 95% CI 0.3-0.9, P<0.01) and had higher risks of 2 year transplant related mortality (Hazard Ratio 1.8, 95% CI, 1.0-2.1, P=0.03) and overall mortality (Hazard Ratio 1.7, 95% CI, 1.2-2.4, P<0.01) than patients with a standard risk graft- versus-host disease. This analysis confirms the Minnesota graft-versus-host disease Risk Score as a valuable bedside tool to define risk in patients with acute graft-versus-host disease. A tailored approach to upfront acute graft- versus-host disease therapy based upon the Minnesota Risk Score may improve outcomes and facilitate testing of novel treatments in these patients.
Introduction
Acute graft-versus-host disease (GvHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT).2 Immediate, real time risk determination at diagnosis may facilitate initiation of more appropri- ate and potentially effective upfront therapy. In 2015, we developed a novel GvHD Risk Score based on the number of organs involved and severity of GvHD at the onset of systemic steroid treatment in 1723 patients from four centers and the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) treated from 1990-2007.1 Using clinical groupings, descriptive statistics and recursive partition- ing, we identified poorly responsive, high-risk (HR) acute GvHD defined by the number of involved organs and organ stage, thus determining the severity of GvHD at onset. HR-GvHD is defined as either skin stage 4; lower gastrointestinal (GI) stage 3-4 or liver stage 3-4; or skin stage 3+ and either lower GI 2-4 or liver stage 2- 4 GvHD. Standard risk (SR)-GvHD includes single organ involvement (either stage 1-3 skin or stage 1-2 GI) or 2 organ involvement (either stage 1-3 skin plus stage I GI; or stage 1-3 skin plus stage 1-4 liver). We designed a free web-based program to easily determine the GvHD risk group for a given patient using our refined Risk Score, available at: https://z.umn.edu/MNAcuteGVHDRiskScore. Patients with HR- GvHD were three times less likely to respond to steroid therapy and had a >2 fold increased risk of overall mortality and transplant-related mortality (TRM) than patients in the SR-GvHD group.1
Ferrata Storti Foundation
Haematologica 2020 Volume 105(2):519-524
Correspondence:
MARGARET L. MACMILLAN
macmi002@umn.edu
Received: March 29, 2019. Accepted: Juy 12, 2019. Pre-published: Juy 18, 2019.
doi:10.3324/haematol.2019.220970
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/2/519
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