T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms
BackgroundT-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 TC...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.884397/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Marta Gonzalez-Vicent |
| collection | DOAJ |
| description | BackgroundT-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.MethodsA 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.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 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.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. |
| first_indexed | 2024-04-13T19:03:31Z |
| format | Article |
| id | doaj.art-79077ef33ef34541ac3aa18390af5be3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T19:03:31Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-79077ef33ef34541ac3aa18390af5be32022-12-22T02:34:01ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.884397884397T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion PlatformsMarta Gonzalez-Vicent0Blanca Molina1Ivan Lopez2Josune Zubicaray3Julia Ruiz4Jose Luis Vicario5Elena Sebastián6June Iriondo7Ana Castillo8Lorea Abad9Manuel Ramirez10Julian Sevilla11Miguel A. Diaz12Hematopoietic Stem Cell Transplantation and Cellular Therapy Unit, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainHematopoietic Stem Cell Transplantation and Cellular Therapy Unit, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainHematopoietic Stem Cell Transplantation and Cellular Therapy Unit, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainDivision of Hematology, Blood Bank and Graft Manipulation Unit, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainHematopoietic Stem Cell Transplantation and Cellular Therapy Unit, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainHistocompatibility Lab, Community Transfusion Center of Madrid, Madrid, SpainDivision of Hematology, Blood Bank and Graft Manipulation Unit, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainDivision of Hematology, Blood Bank and Graft Manipulation Unit, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainOncology/Hematology Lab, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainOncology/Hematology Lab, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainOncology/Hematology Lab, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainDivision of Hematology, Blood Bank and Graft Manipulation Unit, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainHematopoietic Stem Cell Transplantation and Cellular Therapy Unit, Hospital Infantil Universitario “Niño Jesus” Madrid, Madrid, SpainBackgroundT-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.MethodsA 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.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 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.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.https://www.frontiersin.org/articles/10.3389/fonc.2022.884397/fullhaploidentical transplanthematological malignanciesimmune reconstitutionchildrenT-cell depletion |
| spellingShingle | 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 T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms Frontiers in Oncology haploidentical transplant hematological malignancies immune reconstitution children T-cell depletion |
| title | T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms |
| title_full | T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms |
| title_fullStr | T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms |
| title_full_unstemmed | T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms |
| title_short | T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms |
| title_sort | t cell depleted haploidentical transplantation in children with hematological malignancies a comparison between cd3 cd19 and tcrαβ cd19 depletion platforms |
| topic | haploidentical transplant hematological malignancies immune reconstitution children T-cell depletion |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.884397/full |
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