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TCR-αβ/CD 19 Depleted Graft Versus T Replete Graft With Post-Transplant Cyclophosphamide in Children Undergoing
Anuraag Reddy Nalla1, Kavitha Ganesan1, Vijayshree Muthukumar1
1Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, Tamil Nadu, India.
Insights
T-cell depleted haploidentical stem cell transplants show superior survival in children with inborn errors of immunity compared to T-replete grafts. Viral reactivation remains a challenge, but strategies like Letermovir prophylaxis may improve outcomes.
Area of Science:
- Immunology
- Hematology
- Pediatrics
Background:
- Inborn errors of immunity (IEI) pose significant challenges in pediatric healthcare.
- Haploidentical hematopoietic stem cell transplantation (HSCT) offers a viable treatment option for IEI.
- Comparing T-cell depleted grafts with T-replete grafts using post-transplant cyclophosphamide (PTCY) is crucial for optimizing HSCT outcomes.
Purpose of the Study:
- To evaluate the efficacy and survival rates of TCRαβ/CD19-depleted versus T-replete grafts in pediatric IEI patients undergoing haploidentical HSCT.
- To compare engraftment, graft-versus-host disease (GvHD), and overall survival between the two graft types.
Main Methods:
- Retrospective analysis of 230 children (birth to 18 years) with IEI who underwent HSCT.
- Focus on 105 patients who received haploidentical HSCT between April 2009 and September 2024.
- Comparison of outcomes between 65 patients receiving TCR-αβ/CD19-depleted grafts and 40 patients receiving T-replete grafts with PTCY.
Main Results:
- No significant differences in engraftment rates (89% vs. 85%) or acute/chronic GvHD (8.6%/12% vs. 15%/17.5%) between T-depleted and T-replete groups.
- Overall 5-year survival was 62% for the T-depleted group versus 54% for the T-replete group.
- Survival was significantly higher in younger children (<2 years) in the T-depleted cohort (60% vs. 37%, p=0.001).
Conclusions:
- TCRαβ/CD19-depleted haploidentical HSCT demonstrates superior survival compared to T-replete grafts with PTCY in pediatric IEI.
- Viral reactivation persists as a significant complication requiring management.
- Strategies such as Letermovir prophylaxis and memory cell add-back are proposed to further enhance survival rates.
Background:
The study aimed to analyze the outcomes of TCRαβ/CD19-depleted and T-replete graft with post-transplant cyclophosphamide (PTCY) in haploidentical hematopoietic stem cell transplantation (HSCT) in inborn errors of immunity (IEI).
Patients And Methods:
We performed a retrospective analysis of children from birth to 18 years of age with IEI who underwent haploidentical HSCT between April 2009 and September 2024, with a minimum follow-up period of 12 months.
Results:
A total of 230 children with IEI underwent HSCT in the 15-year period, where 105 (45%) underwent haploidentical HSCT and were included in the analysis with a follow up period of 0.5 to 170 months. TCR-αβ/CD19-depleted HSCT was done in 65 (62%) children, while T-replete graft with PTCY was used in 40 (38%) children. There was no significant difference in engraftment rates, acute and chronic graft versus host disease rates between both the cohorts: T-depleted group-89%, 8.6%, 12% respectively versus T-replete group-85%, 15%, 17.5% respectively. The 5-year overall survival was 62% (95% CI: 48%-73%) in the TCR-αβ/CD 19-depleted cohort in comparison to 54% (95% CI: 48% to 73%) in the PTCY cohort. When the survival was compared in children less than 2 years of age, it was 60% in the TCR-αβ/CD 19 depleted cohort versus 37% in PTCY cohort (p value of 0.001).
Conclusion:
Survival was superior in the T depleted cohort as compared to the T replete group, with viral reactivation remaining a persisting challenge. Letermovir prophylaxis and memory cell add-back would be potential strategies to improve survival.
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