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Outcome of adult t(6;9) AML
Figure 1. Cumulative incidence of relapse (CIR) and cumulative incidence of death (CID) according to treatment strategy. CIR and CID included only patients achieving complete remission.
Table 2. Relapse-free and overall survival according to treatment strategy in first complete remission.
5-years RFS %
Allo-HCT (n=89) 45
Consolidation chemotherapy 7
(n=55)
95%-CI
35-59
3-19
5-year OS %
53
23
95%-CI
42-66
13-38
allo-HCT:allogeneic hematopoietic cell transplantation;CI:confidence interval;OS:overall survival;RFS:relapse-free survival.Median follow up was 5.43 years (95%CI:3.93-6.53 years).
patients. Forty-one patients received reduced-intensity conditioning. Source of donor was matched related in 46, matched unrelated in 54, haplo-identical in 11, cord blood in five, and unknown in one of the 117 patients.
Cumulative incidence of relapse, cumulative incidence of death in complete remission and survival
The median follow up of the entire cohort was 5.43 years (95%CI: 3.93-6.53 years). Median and 5-year OS of the entire cohort were 2.25 years (95%CI: 1.56-3.70 years) and 38% (95%CI: 31-47%). Five-year RFS and OS were 45% (95%CI: 35-59%) and 53% (95%CI: 42-66%) in patients proceeding to allo-HCT in CR1 after induction therapy (n=89), as compared to 7% (95%CI: 3-19%;) and 23% (95%CI: 13-38%), respectively, in those who received consolidation chemotherapy alone (n=55) (Table 2). In subgroup analysis, presence of FLT3-ITD had no prognostic impact on OS, either in the total analyzed cohort (P=0.093), or in those patients proceeding to allo- HCT (P=0.39). Similarly, additional chromosomal abnor- malities had no prognostic impact on OS in the men- tioned cohorts (P=0.49; P=0.86; respectively). A Cox regression analysis revealed, after limited backward selec- tion, higher WBC [hazard ratio (HR) for log10, 1.62; 95%CI: 1.12-2.29; P=0.005] and age (HR for a difference of 10 years, 1.29; 95%CI: 1.12-1.50; P=0.001) as unfavor- able variables, whereas platelet count, type of AML (de novo vs. therapy-related/secondary after previous MDS/myeloproliferative neoplasm), presence of FLT3- ITD, and additional cytogenetic aberrations had no impact on prognosis.
In 144 patients achieving CR1, CIR was significantly lower in patients proceeding to allo-HCT (n=89) as com- pared to those who were treated with consolidation chemotherapy (n=55; P<0.001). As expected, CID tended to be higher in patients proceeding to allo-HCT as com- pared to those receiving consolidation chemotherapy (P=0.08) (Figure 1).
One hundred and seventeen patients proceeded to allo- HCT in CR1 (n=89) or CR2 (n=10), or with refractory (n=15) or relapsed (n=3) disease. The influence of allo- HCT assessed as a time-dependent co-variable as post remission therapy on OS is illustrated by a Simon Makuch plot (Figure 2). In addition, Figure 3 shows a Kaplan Meier plot illustrating the influence of allo-HCT performed in CR1 on RFS. The Mantel-Byar tests revealed a significantly better OS (P=0.001) and RFS (P<0.0001) for patients proceeding to allo-HCT in CR1 as compared to consolidation with chemotherapy only. Neither type of conditioning (P=0.90) nor donor type (matched related donor versus matched unrelated/hap- loidentical/cord blood donor; P=0.30) had an impact on outcome. There was no difference in OS measured from date of transplant in patients transplanted in CR1 or CR2 as compared to those with active disease (P=0.66) (Figure 4). An Andersen-Gill model including allo-HCT as a time- dependent variable revealed higher WBC and older age as unfavorable variables, whereas allo-HCT performed either in CR or with active disease was associated with a favorable prognosis. Decade of treatment, additional chromosomal abnormalities or FLT3-ITD had no prog- nostic impact (Table 3).
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