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C.E. Dandoy et al.
P=0.01) and 4–10 years (HR 2.29, 95% CI: 1.57–3.33, P<0.0001). Chronic GvHD was higher with HLA-mis- matched cord blood compared to HLA-matched sibling donors (HR 2.04, 95% CI: 1.10–3.67, P=0.02). Chronic GvHD risks did not differ between other donor groups (data not shown).
Non-relapse mortality and relapse
Non-relapse mortality was higher with TBI-containing regimens (Table 2, Figure 1A). The 1- and 5-year incidence of non-relapse mortality with TBI-containing regimens were 17% (95% CI: 12–22) and 22% (95% CI: 16–28). The corresponding incidence with non-TBI regimens were 8% (95% CI: 6–11) and 11% (95% CI: 8–15). Compared to patients aged 4–10 years, non-relapse mortality was higher in patients aged 11–21 years (HR 1.99, 95% CI: 1.15–3.46, P=0.01) but not in those aged ≤3 years (HR 1.71, 95% CI: 0.85–3.44, P=0.13). Infections were higher with TBI-con- taining compared to non-TBI regimens (Table 3A). Veno- occlusive disease was lower with TBI-containing regimens (Table 3A). Patients who survived at least 1 year after trans- plantation in remission were evaluable for organ dysfunc- tion (Table 3B). Endocrine dysfunction (thyroid or gonadal) was higher with TBI-containing regimens. Pulmonary, car- diac and renal complications did not differ between treat- ment groups.
Relapse risks were lower in TBI-containing regimens (Table 2, Figure 1B). The 1- and 5-year incidence of relapse with TBI-containing regimens were 15% (95% CI: 11–22) and 23% (95% CI: 17– 29). The corresponding relapse inci- dence with non-TBI regimens were 26% (95% CI: 22–31) and 37% (95% CI: 32–42), P<0.0001. Relapse risks did not differ between patients aged 4-10 and 11-21 years (HR 1.17, 95% CI: 0.82–1.69, P=0.39). Relapse was higher in patients aged ≤3 years compared to those aged 4-10 years (HR 2.49, 95% CI: 1.68–3.69, P<0.0001) and 11–21 years (HR 2.12, 95% CI: 1.51–2.98, P<0.0001). Compared to bone marrow and central nervous system involvement at diagnosis,
relapse risks were higher in patients with bone marrow involvement alone (HR 1.93, 95% CI: 1.27–2.93, P=0.002) and bone marrow with extramedullary site(s) excluding central nervous system involvement (HR 1.88, 95% CI: 1.01–3.50, P=0.04). Acute grade 2-4 GvHD was associated with lower relapse risk (HR 0.63, 95% CI: 0.44–0.89, P=0.008) but this was independent of conditioning regi- men. The effect of acute grade 3-4 (HR 0.65, 95% CI: 0.39– 1.09, P=0.10) and chronic GvHD (HR 0.74, 95% CI: 0.48– 1.15, P=0.19) on relapse did not meet the level of signifi- cance that was set a priori.
Overall and leukemia-free survival
There were no differences in overall or leukemia-free sur- vival by treatment groups (Table 2, Figure 2A and B). Age was associated with both overall and leukemia-free survival and cytogenetic risk with leukemia-free survival. Compared to patients aged 4-10 years, survival was lower for those aged 11– 21 years (HR 1.82, 95% CI: 1.28–2.59, P<0.0001) and ≤3 years (HR 2.79, 95% CI: 1.90–4.10, P<0.0001). Survival was also lower in patients aged ≤3 years compared to those aged 11–21 years (HR 1.52, 95% CI: 1.14–2.08, P=0.005). Compared to favorable cytogenetics, leukemia-free survival was lower with intermediate risk (HR 1.85, 95% CI: 1.10–3.09, P=0.0198) and poor risk (HR 2.46, 95% CI: 1.42–4.27, P=0.0013). The 5-year overall sur- vival was 61% (95% CI: 54–68) and 61% (95% CI: 56–66) after TBI-containing and non-TBI containing regimens. The corresponding leukemia-free survival was 53% (95% CI: 46–60) and 53% (95% CI: 48–58).
Transplant period
As the current analysis included patients transplanted between 2008 and 2016, we tested for an effect of trans- plant period (2012-2016 vs. 2008-2011) on non-relapse mor- tality (HR 0.75, 95% CI 0.48 - 21.17, P=0.21), relapse (HR 1.04, 95% CI: 0.78–1.41, P=0.78), overall (HR 0.93, 95% CI: 0.71– 1.22, P=0.62) and leukemia-free survival (HR 0.96,
AB
Figure 1. Non-relapse mortality and relapse. (A) Cumulative incidence of non-relapse mortality with total body irradiation (TBI)-containing and non-TBI regimens, (B) cumulative incidence of relapse with TBI-containing and non-TBI regimens.
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