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M.L. MacMillan et al.
Months after initiation of steroid GvHD therapy
Figure 2. Cumulative incidence of TRM at 6 months after onset of steroid therapy by Minnesota GvHD Risk Score.
Table 2. GvHD organ stage at onset of steroid treatment.
OrganStage 0 1 2 3 4
P<0.01
Skin
Liver Lower GI Upper GI
121 (34%)
343 (97%) 200 (56%) 232 (65%)
26 (7%)
7 (2%) 37 (10%) 123 (35%)
52 (15%)
2 (1%) 56 (16%)
150 (42%)
2 (1%) 48 (14%)
6 (2%)
1 (<1%) 14 (4%)
index (CI) score ≥3 (HzR 1.7, 95% CI,1.2-2.5, P<0.01). There was a trend toward lower mortality in early onset GvHD (HzR 0.71, 95% CI, 0.50-1.01, P=0.06). There were no statistically significant interactions with other covari- ates.
Two years after the initiation of the steroid therapy, 92 patients had developed chronic GvHD for a cumulative incidence of 26% (95% CI 21-31%). No differences in the incidence of chronic GvHD were observed in those with SR or HR acute GvHD (28% verus 20%, P=0.54). Risks of chronic GvHD, however, were significantly lower in UCB recipients (HzR 0.6, 95% CI, 0.5-0.9, P=0.01) and in early onset GvHD (HzR 0.95, 95% CI, 0.92-0.98, P<0.01), but were higher in patients greater than 18 years of age ((HzR >2.8), P≤0.01).
Discussion
We previously demonstrated that our refined multicen- ter Minnesota GvHD Risk Score, based upon the initial GvHD stage, serves as a better predictor of response and survival than either our previously published GVHD Risk Score based upon the initial GvHD grade, or the reported Minnesota or CIBMTR GvHD grading systems.14 To vali- date this refined Minnesota GvHD Risk Score, we exam- ined a new, contemporary cohort of patients with acute GvHD treated at the University of Minnesota. This new cohort had a greater proportion of patients receiving RIC
and more UCB recipients. Our results confirm that the Minnesota GvHD Risk Score, based upon the initial GvHD stage, is a valuable and immediately available bed- side tool to define the risk in patients with acute GvHD. It also predicts the outcomes of response, survival and TRM better than other published GvHD Risk Scores determined by clinical grading criteria. These data suggest that a tailored approach to upfront GvHD therapy based upon this Minnesota acute GvHD Risk Score and other risk factors should be considered in order to improve out- comes and to plan novel treatment studies in patients with acute GvHD.
In 1974, the Glucksberg grading system was developed by examining the clinical severity of acute GvHD in 43 adult patients who received matched sibling donor (MSD) transplants after myeloablative conditioning from 1969-1973.15 This grading system was later modified, but in all iterations, grade III-IV acute GvHD was considered high risk. 4,12,16 In 1997, the CIBMTR grading system was developed from 2129 adult who received MSD trans- plants after myeloablative conditioning from 1986-1992, and patients with grades C and D are deemed high risk based upon subsequent survival, yet GvHD treatment response was not examined.3 However, clinical observa- tions suggest there are some patients with grade III GvHD who do well while some patients with grade II GvHD fare poorly.
We first attempted to better identify HR acute GvHD at diagnosis by examining the outcomes of 864 patients at
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haematologica | 2020; 105(2)