A higher CD34 + cell dose correlates with better event-free survival after KIR-ligand mismatched cord blood transplantation for childhood acute myeloid leukemia

A total of 299 patients were included, consisting of 238 patients in the KIR-L match group and 61 patients in the KIR-L mismatch group (Additional file 1: Figure S1). The background characteristics of two groups were overall similar (Additional file 1: Table S1). The median follow-up period for survivors was 7.2 years (range, 0.1–22.4). The cumulative incidence rates of neutrophil recovery, platelet engraftment, and acute/chronic graft-versus-host disease did not differ significantly between the groups (Additional file 1: Figure S2-4).

The 5-year event-free survival (5y-EFS) rate was 69.8% for the KIR-L match group and 74.0% for the KIR-L mismatch group (p = 0.490; Table 1). The 5-year cumulative incidences of relapse were 22.3% and 15.2% (p = 0.257), and the 5-year cumulative incidences of non-relapse mortality (NRM) were 7.9% and 10.8% (p = 0.605) for the KIR-L match and mismatch groups, respectively, and the causes of death were similar between the groups (Additional file 1: Tables S2 and S3).

Table 1 Univariate and multivariate analysis for event-free survival

As a number of previous studies have suggested that CD34 + cell doses have an impact on the survival and/or engraftment [9,10,11], we stratified patients by CD34 + cell dose, and univariate analysis revealed a significant correlation between higher CD34 + cell dose and better EFS in the KIR-L mismatch group, as 5y-EFS was 34.3% for those with less than 1 × 105/kg, 71.8% for those with 1–2 × 105/kg, 86.7% for those with 2–3 × 105/kg, and 90.9% for those with ≥ 3 × 105/kg CD34 + cell doses (Fig. 1B, p = 0.006). On the other hand, this correlation was not detected in the KIR-L match group (Fig. 1A; p = 0.325). The impacts of CD34 + cell doses on EFS in the KIR-L mismatch group was attributed not only to the lower NRM but also to the lower relapse rate among those receiving higher doses, although neither was significant according to univariate analysis (Fig. 1C and D). These results were similar when we classified the patients into two groups: one with CD34 + cell doses less than the median (referred to as CD34low) and the other with CD34 + cell doses equal to or greater than the median (CD34high) (Additional file 1: Figure S5).

Fig. 1figure 1

Event-free survival according to the infused CD34 + cell dose in the (A) KIR-ligand match group and (B) KIR-ligand mismatch group. The cumulative incidence of (C) relapse and (D) non-relapse mortality according to the infused CD34 + cell dose in the KIR-ligand mismatch group is also shown. EFS, event-free survival; CIR, cumulative incidence of relapse; CINRM, cumulative incidence of non-relapse mortality; CI, confidence interval; NA, not available; KIR, killer immunoglobulin-like receptor

In the multivariate analysis for EFS, the KIR-Lmismatch–CD34high (≥ median dose) subgroup was identified as an independent favorable prognostic factor (hazard ratio = 0.19, p = 0.029; Table 1). We also performed multivariate analysis for the incidence of relapse, and the KIR-Lmismatch–CD34high subgroup was identified as an independent favorable prognostic factor (hazard ratio = 0.09, p = 0.021; Additional file 1: Table S4).

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