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High uric acid levels and increased mortality after alloSCT
AB
≤ 4.3 mg/dL
≤ 4.3 mg/dL
> 4.3 mg/dL
> 4.3 mg/dL
C
≤ 4.3 mg/dL
Figure 2. Non-relapse mortality, relapse incidence and infection-related mortality at one year after allogeneic stem cell transplantation. Incidence of non-relapse mortality (NRM) (A), relapse incidence (RI) (B) and infection-related mortality (C) after allogeneic stem cell transplanta- tion (alloSCT) in cohorts according to uric acid serum levels prior to alloSCT: patients with high uric acid serum levels (blue line), patients with low uric acid levels (red line).
> 4.3 mg/dL
Table 3. Multivariate global comparison. Uric acid >4.3 mg/dL
versus ≤4,3 mg/dL Overall Survival
HR
2,83
1,59
1,59
2,65
0,96
1,08
1,52
1,68
95%CI P
Progression Free Survival Relapse Incidence Non-Relapse Mortality Chronic GvHD
Extensive Chronic GvHD
Acute GvHD II-IV
Acute GvHD III-IV
1,06 - 2,39 0.03 1,02 - 2,49 0.04
1,41 - 5,01
0,63 -1,45 0.84 0,62 - 1,88 0.79 0,95 - 2,43 0.08 0,88 - 3,19 0.11
In animal experiments and in a clinical pilot study the depletion of uric acid with rasburicase led to a reduced fre- quency of severe GvHD.7,8 Therefore, our initial hypothe- sis was to primarily find an association between uric acid with acute GvHD and then secondarily with NRM. However, we found a strong positive association of uric acid levels with mortality after alloSCT whereas the asso- ciation between uric acid levels and acute GvHD inci- dence was not statistically significant. One of the reasons could be the low incidence of GvHD in our cohort due to the patient characteristics of human leukocyte antigen (HLA)-identical sibling transplant with a high proportion of anti-thymocyte globulin (ATG) use. The use of in vivo T-cell depletion with ATG in HLA-identical sibling
1,72 - 4,68
<0.0001
0.003
GvHD: graft-versus-host disease; HR: hazard ratio; CI: confidence interval.
tumours, we were interested in a possible connection of uric acid levels and disease relapse. We found that the relapse incidence in all patients at 1 year was 13%. The relapse incidence was moderately increased in the cohort with higher uric acid levels (Figure 2B, Table 3 and Table 4, univariate HR 1.6, 95% CI: 1.0-2.5; P=0.09; multivariate HR 1.6, 95% CI: 1.0-2.5, P=0.04).
Discussion
This prospective study identifies uric acid levels, taken before start of conditioning therapy, as a laboratory bio- marker to predict mortality after alloSCT.
haematologica | 2020; 105(7)
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