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M.L. MacMillan et al.
Figure 1. Response by Minnesota GvHD Risk Score.
As measured by the net reclassification index, the Minnesota GvHD Risk Score improves both the true-pos- itive and false-positive rates and is a better predictor of response to upfront steroid therapy, survival and TRM than other published GvHD Risk Scores based upon clini- cal grading criteria.1 Our previous analysis revealed that this GvHD Risk Score would reclassify 83% patients grad- ed by the Center for International Blood and Marrow Transplant Research (CIBMTR) grading system3 and 27% if the Minnesota GvHD grading system4,5 were used allowing for more appropriate, risk stratified therapy at initial GvHD diagnosis.3-6
To validate this Minnesota GvHD Risk Score in a con- temporary cohort with greater variety of conditioning reg- imens and donor grafts, we examined an independent cohort of 355 patients diagnosed with acute GvHD who were treated with systemic steroids as initial therapy at the University of Minnesota.
Methods
Between December 2007 and December 2016, 355 first allo- geneic HCT patients developed grade I-IV acute GvHD and were treated with prednisone 60 mg/m2/day per os (PO) (or methyl- prednisolone 48 mg/m2/day intravenously (IV)) as initial therapy and are included in this analysis. Patients with grade I GvHD not treated with systemic therapy were excluded from this analysis. All HCT protocols were reviewed and approved by the Masonic Cancer Center Protocol Review Committee and the Institutional Review Board at the University of Minnesota.
Patient and transplant characteristics
Patient and transplant characteristics are shown in Table 1 for our new cohort of 355 patients as well as our old cohort of 1723 patients for comparison. The date of transplant did not overlap between the two groups. The median patient age was similar being 49 years (range, 0.2-75) and 40 years (range 0.2-76). In each cohort, 62% were males and the majority had a malignant disease.
In both groups approximately 1/3 of patients received a human leukocyte antigen (HLA)-matched sibling bone marrow (BM) or peripheral blood stem cell (PBSC) donor graft. In our new cohort, there were fewer HLA matched or mismatched unrelated donor (URD) grafts used. A much greater proportion of patients received an umbilical cord blood (UCB) graft; now 55% compared to only 15% previously. Details of the preparative therapy, GvHD pro- phylaxis and supportive therapies have been previously reported. 7-10 In the new cohort, 50% patients received reduced intensity conditioning (RIC) compared to only 26% patients previously. In our new cohort, GvHD prophylaxis consisted of cyclosporine A (CSA) or tacrolimus based therapy in 92% of patients, ex vivo T-cell depletion in 1% of patients, and sirolimus plus mycopheno- late mofetil (MMF) in 7% of patients.
GvHD therapy and measurement of response to prednisone
All patients were to receive daily, thrice divided doses of pred- nisone 60 mg/m2/day orally (or methylprednisolone IV equivalent, 48 mg/m2) for seven consecutive days, followed by daily pred- nisone for seven days as initial therapy for acute GvHD. Patients were maintained on therapeutic levels of CSA, tacrolimus or sirolimus. Additionally, patients with skin acute GvHD were treat- ed with topical 0.1% triamcinolone cream or 1% hydrocortisone cream (for facial rash) three times daily. If a response to prednisone was observed, patients continued therapy with oral prednisone 60 mg/m2/day through day 14 and then commenced a taper of steroids over eight weeks.11,12 Response to therapy was evaluated by the attending physician and prospectively recorded weekly in the University of Minnesota BMT Database by determining the GvHD clinical stage score for each time point (±3 days).13 Additional detail of GvHD data collection and scoring, supportive care and statistical analyses are detailed in the Online Supplementary Methods section.
Results
For the entire cohort, the median time from HCT to ini- tiation of steroid therapy was 37 days (range 10-170,
P=0.02 P
520
haematologica | 2020; 105(2)