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

Marta Gonzalez-Vicent; Blanca Molina; Ivan Lopez; Josune Zubicaray; Julia Ruiz; Jose Luis Vicario; Elena Sebastián; June Iriondo; Ana Castillo; Lorea Abad; Manuel Ramirez; Julian Sevilla; Miguel A Diaz

doi:10.3389/fonc.2022.884397

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

Front Oncol. 2022 Jun 20:12:884397. doi: 10.3389/fonc.2022.884397. eCollection 2022.

Authors

Affiliations

¹ Hematopoietic Stem Cell Transplantation and Cellular Therapy Unit, Hospital Infantil Universitario "Niño Jesus" Madrid, Madrid, Spain.
² Division of Hematology, Blood Bank and Graft Manipulation Unit, Hospital Infantil Universitario "Niño Jesus" Madrid, Madrid, Spain.
³ Histocompatibility Lab, Community Transfusion Center of Madrid, Madrid, Spain.
⁴ Oncology/Hematology Lab, Hospital Infantil Universitario "Niño Jesus" Madrid, Madrid, Spain.

Abstract

Background: T-cell depleted (TCD) haploidentical transplantation using CD3+/CD19+ and TCRαβ+/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 TCRαβ+/CD19+ platforms.

Methods: A total of 159 children with leukemia (ALL=80) (AML=79) that received a TCD haploidentical transplantation using either CD3+/CD19+ (n=79) or TCRαβ+/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 TCRαβ+/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 TCRαβ+/CD19+ group (35.32x10⁶/kg and 0.06 x10⁶/Kg) than in the CD3+/CD19 group (24.6x10⁶/Kg and 0.25 x10⁶/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 TCRαβ+/CD19+ group.

Results: Engraftment 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 TCRαβ+/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 TCRαβ+/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.

Conclusions: Our 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.

Keywords: T-cell depletion; children; haploidentical transplant; hematological malignancies; immune reconstitution.