Patient characteristics
Among the 123 AML patients analyzed, 46.3% (n=57) were females. Median age was 31 years (range 12 to 62 years), one patient was more than 60 years old (0.81%). Median follow-up was 46 months (range 1 to 94 months). According to the AML-DRG model, 68, 43 and 12 patients were in low-, intermediate- and high-risk group, respectively. According to the AML-HCT-CR model, 68, 25, 18 and 12 patients were in low-, intermediate-, high- and very high-risk group, respectively. The basic clinical data of the patients were shown in Table 1.
GVHD
For the entire cohort, the cumulative incidence of grade II to IV acute GVHD at day 100 was 18.7% (95% CI 15.4-22), the cumulative incidence of all-grade chronic GVHD at 2 years was 25.4% (95% CI 21.9-28.9). The cumulative 100-day incidence of grade II to IV acute GVHD for the low-, intermediate- and high-risk AML-DRG groups was 19.1% (95% CI 16.6-21.7), 18.6% (95% CI 11.3-25.9) and 16.7% (95% CI 0-36.0), differences are not statistically significant (P=0.980). The incidence for all-grade chronic GVHD at 2 years was 31.3% (95% CI 25.6-37.0), 20.9% (95% CI 13.4-28.4) and 8.3% (95% CI 0-25.8), respectively (p=0.211) (Table 2) .
For the AML-HCT-CR model, the cumulative 100-day incidence of grade II to IV acute GVHD for the low-, intermediate-, high- and very high-risk groups was 19.1% (95% CI 13.9-24.3), 12.0% (95% CI 1.9-22.1), 27.8% (95% CI 12.6-43.0) and 16.7% (95% CI 0.0-36.2), respectively (p=0.610). The incidence for all-grade chronic GVHD at 2 years was 31.3% (95% CI 25.6-37.0), 28.0% (95% CI 16.1-39.9), 11.1% (95% CI 0-24.1) and 8.3% (95% CI 0-26.5), respectively (p=0.252) (Table 2).
Relapse and NRM
For the entire cohort, the 3-year cumulative incidences of relapse and NRM were 23.0% (95% CI 19.6-26.4) and 28.6% (95% CI 25.0-32.2), respectively. Reasons for relapse were hematological in 20 patients, extramedullary in 3 patients, and hematological plus extramedullary in 5 patients. Reasons for NRM were infection in 22 patients, acute GVHD in 11 patients, and hemorrhage in 5 patients.
The 3-year cumulative incidence of relapse for the low-, intermediate- and high-risk AML-DRG groups was 13.6% (95% CI 8.7-18.5), 30.2% (95%CI 22.3-38.2) and 50.0% (95% CI 27.6-72.4), respectively (p=0.002) (Figure 1B), with the corresponding 3-year NRM was 22.3% (95% CI 17.0-27.7), 34.9% (95% CI 26.8-43.0) and 41.7% (95% CI 19.0-64.4), differences are not statistically (p=0.314) (Figure 1C). The 3-year cumulative incidence of relapse for the low-, intermediate-, high- and very high-risk AML-HCT-CR groups was13.6% (95% CI 8.7-18.5), 24.0% (95% CI 12.4-35.6), 44.4% (95% CI 28.3-60.6) and 41.7% (95% CI 19.7-63.6), respectively (p=0.005) (Figure 2B), with the corresponding 3-year NRM was 22.3% (95% CI 17.0-27.7), 24.0% (95% CI 12.4-35.6), 44.4% (95% CI 28.2-60.7) and 50.0% (95% CI 27.3-72.7), differences are not statistically significant (p=0.095) (Figure 2C, Table 2).
OS and PFS
The 3-year OS and PFS of the entire cohort were 49.1% (95% CI 41.0-58.9) and 48.4% (95% CI 40.3-58.1). Patients in low-, intermediate- and high-risk AML-DRG groups had median OS of 33.5 (1~94), 10 (1~60) and 4 (1~69) months, respectively (p<0.001), with the corresponding 3-year OS of 65.4% (95% CI 54.9-78.0), 34.9% (95% CI 23.2-52.5) and 8.3% (95% CI 1.3-54.4), respectively (p<0.001). The 3-year PFS were 64.0% (95% CI 53.5-76.7), 34.9% (95% CI 23.2-52.5) and 8.3% (95% CI 1.3-54.4), respectively (p<0.001) (Figure 1A). The median OS for the low-, intermediate-, high- and very high-risk AML-HCT-CR groups were 33.5 (1~94), 28 (2~60), 6.5 (1~43) and 3.5 (1~69) months, respectively (p<0.001), with the corresponding 3-year OS of 65.4% (95% CI 54.9-78.0), 52.0% (95% CI 35.7-75.8), 11.1% (95% CI 3.0-41.0) and 8.3% (95% CI 1.3-54.4), respectively (p<0.001) (Figure 2A). The 3-year PFS were 64.0% (95% CI 53.5-76.7), 52.0% (95% CI 35.7-75.8), 11.1% (95% CI 3.0-41.0) and 8.3% (95% CI 1.3-54.4), respectively (p<0.001) (Table 2).
In univariable analysis for OS, patients with intermediate and high-risk AML-DRG groups had a significantly increased risk of death with hazard ratio (HR) of 2.29 (95% CI 1.3-3.9; p=0.003) and 5.14 (95% CI 2.5-10.6; p<0.001), respectively when compared with the low-risk group. Also, the risk of death was higher in high-risk group compared with the intermediate-risk group (HR 2.26, 95% CI 1.1-4.6; p=0.023), confirming the ability of the AML-DRG model in post-transplant survival prediction. For AML-HCT-CR groups, patients with high (HR 4.43, 95% CI 2.3-8.5; p<0.001) and very high-risk groups (HR 5.82, 95% CI 2.8-12.0; p<0.001) had significantly increased risk of death than low-risk group, while there was no difference between low and intermediate-risk (HR 1.37, 95% CI 0.7-2.7; p=0.365) and between high and very high group (HR 1.47,95% CI 0.7-3.2; p=0.329). Similar results were found in a univariable analysis for PFS as summarized in Table 3.
Multivariate analysis
Multivariable analysis confirmed that the HCT-CR and AML-HCT-CR models could be used to predict the OS of patients in different risk groups after adjusted for other variables including age, sex, conditioning type, transplant modality, and stem cell source. See Table 4 for details.
Comparison of prognostic stratification:
The C-indexes of the AML-DRG, AML-HCT-CR, DRI, ELN2017 genetic risk, and HCT-CI/Age model were 0.680 (95% CI 0.586-0.774), 0.705 (95% CI 0.613-0.797), 0.605 (95% CI 0.506-0.705), 0.519 (95% CI 0.416-0.621) and 0.601 (95% CI 0.501-0.700), respectively. Compared with the DRI model and the HCT-CI/Age, the AML-DRG and AML-HCT-CR models had significantly better discrimination ability on OS prediction with C-index. The risk assessment ability of AML-DRG and AML-HCT-CR may be better than that of ELN2017 genetic risk, DRI and HCT-CI/Age models.