T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+and TCR alpha beta+/CD19+Depletion Platforms

FRONTIERS IN ONCOLOGY(2022)

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摘要
BackgroundT-cell depleted (TCD) haploidentical transplantation using CD3+/CD19+ and TCR alpha beta+/CD19+ depletion techniques has been increasingly used in children with hematological malignancies. We present a retrospective study aimed to compare transplant outcomes in children with leukemia receiving a TCD haploidentical transplant using either CD3+/CD19+ or TCR alpha beta+/CD19+ platforms. MethodsA total of 159 children with leukemia (ALL=80) (AML=79) that received a TCD haploidentical transplantation using either CD3+/CD19+ (n=79) or TCR alpha beta+/CD19+ (n=80) platforms between 2005 and 2020 were included. Median age was 9 years in both groups. There were no differences in patient, donor, and transplant characteristics between groups except for donor KIR B genotype more frequent in the TCR alpha beta+/CD19+ group (91%) than in the CD3+/CD19+ group (76%) (p=0.009) and a high number of NK+ cells and lower CD19+ cells infused in the TCR alpha beta+/CD19+ group (35.32x10(6)/kg and 0.06 x10(6)/Kg) than in the CD3+/CD19 group (24.6x10(6)/Kg and 0.25 x10(6)/Kg) (p=0.04 and p=0.0001), respectively. Conditioning was based on TBF. Median follow-up for survivors was 11 years (range; 8-16 y) in CD3+/CD19+ group and 5 years (range; 2-9 y) in the TCR alpha beta+/CD19+ group. ResultsEngraftment kinetics were similar in both groups (13 days for neutrophils and 10 days for platelets). There was no difference in the incidence of acute GvHD II-IV (29 +/- 5% in the CD3+/CD19+ group vs 38 +/- 5% in the TCR alpha beta+/CD19+ group) and chronic GvHD (32 +/- 5% vs 23 +/- 4%, respectively). NRM was 23 +/- 5% in the CD3+/CD19+group vs 21 +/- 4% in the TCR alpha beta+/CD19+group. Relapse incidence was also similar, 32 +/- 5% vs 34 +/- 6%, respectively. DFS and OS were not different (45 +/- 5% vs 45 +/- 6% and 53 +/- 6% vs 58 +/- 6% respectively). As there were no differences on transplant outcomes between groups, we further analyzed all patients together for risk factors associated with transplant outcomes. On multivariate analysis, we identified that early disease status at transplant (HR: 0.16; 95%CI (0.07-0.35) (p=0.0001), presence of cGvHD (HR: 0.38; 95%CI (0.20-0.70) (p= 0.002), and donor KIR-B genotype (HR: 0.50; 95%CI (0.32-0.90) (p=0.04) were associated with better DFS. ConclusionsOur data suggest that there are no advantages in transplant outcomes between TCD platforms. Risk factors for survival are dependent on disease characteristic, donor KIR genotype, and chronic GvHD rather than the TCD platform used.
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关键词
haploidentical transplant, hematological malignancies, immune reconstitution, children, T-cell depletion
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