Page 52 - Haematologica May 2022

H.T. Greinix et al.
Figure 4. Three-year non-relapse mortality after aGvHD grades II-IV over time. Cumulative incidence estimates were calculated for NRM in a competing risks frame- work with relapse as a competing risk for estimation of NRM. Data are shown according to transplantation periods 1990-1995, 1996-2000, 2001-2005, 2006-2010 and 2011-2015.
had no significant impact on relapse incidence for the cohort as a whole, patients with AML (HR 1.22 (1.08- 1.37); P<0.001) and ALL (HR 1.53 (1.21-1.94), P<0.001) given RIC had a significant increased relapse risk while this was not the case in patients with MDS, respectively.
Outcomes after aGvHD grades III-IV
Survival at 36 months after aGvHD grades III-IV increased significantly (P<0.001) from 22% (19-25%) to 23% (21-25%), 28% (27-30%), 28% (27-30%), and 29% (27-31%) for the periods 1990-1995, 1996-2000, 2001- 2005, 2006-2010, and 2011-2015, respectively (Figure 3B).
In multivariate analysis, URD (HR 1.18 (1.1-1.27); P<0.001), not in CR at HSCT (HR 1.25 (1.17-1.34); P<0.001) and use of ATG/alemtuzumab (HR 1.28 (1.17- 1.4); P<0.001) were all associated with increased mortality after aGvHD grades III-IV. Of note is that mortality decreased in the more recent transplant cohorts treated without ATG/Alemtuzumab (HR 0.74 (0.69-0.8); P<0.001) and treated with ATG/Alemtuzumab (HR 0.86 (0.78-0.95); P=0.002).
Discussion
In retrospective analyses, improvement over time in sur- vival outcome for patients given allogeneic HSCT has been reported in parallel with changes of transplant practices. These include a spectrum of diseases treated with allograft- ing, more frequent use of PBSC rather than BM, adminis- tration of more unrelated instead of related donor grafts, and older patient and donor age.11 Whether outcome improvement over time is also found in patients experienc- ing severe aGvHD is less well known. Therefore, we ana-
lyzed the outcome of patients experiencing severe aGvHD over time in a large patient cohort reported to the EBMT. We observed a significant decrease of aGvHD grades II to IV and grades III to IV over time that was most pronounced in the more recent transplant cohort. Since having an URD compared to a related donor significantly increased the risk for aGvHD in multivariate analysis of our patient cohort, improvements in HLA typing in the more recent transplant years could have an impact on this finding. Over recent years and based on the outcome of numerous studies, the identity of ten alleles in five HLA loci, namely HLA-A, -B, -C, -DRB1, and -DQB1, and using high-resolution typing instead of serologic typing has become the gold standard of URD matching. Several studies have shown an association between allelic mismatches in HLA-A, -B, -C and -DRB1 and higher rates of aGvHD.14-16 Recent developments in clinical diagnosis, improved understanding of pathophysi- ological features, the use of both standard and experimen- tal options for prevention, and the use of biomarkers to tai- lor treatment to individual patients could lead to a further reduction in aGvHD rates in the future.
After adjusting for significant patient-, disease-, and transplant-related variables, patients with aGvHD grades II-IV, in the more recent cohort, had significantly lower NRM and better DFS and OS compared with those in the earlier years. Three-year survival of patients experiencing aGvHD grades II-IV improved significantly over time, reaching 45% for patients given HSCT between 2011 and 2015. Whereas Khoury et al., observed significant improvements in OS over time that was limited to patients treated with tacrolimus-based GvHD prophylax- is, and mostly in those with overall grade II aGvHD, GvHD prophylaxis had no significant impact on OS in our cohorts, in multivariate analysis.12 Of note is that three-
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