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Published on: September 6, 2017
Immune reconstitution in children after haploidentical haematopoietic stem cell transplantation
Saranthorn Apasuthirat1, Nopporn Apiwattanakul1, Usanarat Anurathapan1
1Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Insights
Pediatric patients undergoing haploidentical stem cell transplants with post-transplant cyclophosphamide show delayed immune reconstitution and higher viral infection risks. The addition of anti-T lymphocyte globulin further impedes T cell recovery and increases BK virus reactivation.
Area of Science:
- Immunology
- Hematology
- Pediatric Oncology
Background:
- Immune reconstitution (IR) kinetics in pediatric patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCy) require further investigation.
- Comparison of IR patterns between haploidentical and HLA-matched HSCT in children is essential for understanding post-transplant outcomes.
Purpose of the Study:
- To compare immune reconstitution patterns in pediatric patients after haploidentical HSCT with PTCy versus HLA-matched HSCT.
- To identify risk factors for viral infections in these pediatric HSCT recipients.
Main Methods:
- Prospective measurement of lymphocyte subsets before and up to 12 months after HSCT.
- Monitoring of viral loads for cytomegalovirus (CMV), Epstein-Barr virus, adenovirus, and BK virus (BKV) in blood and urine.
Main Results:
- Haploidentical HSCT recipients exhibited significantly lower median counts of T cells and T helper cells at 1 month post-HSCT compared to HLA-matched recipients.
- Delayed recovery of T cell subsets and B cells was observed in the haploidentical group throughout the first year.
- Increased incidence of BKV hemorrhagic cystitis, blood CMV, and urine adenovirus reactivation was noted in the haploidentical group. Addition of anti-T lymphocyte globulin (ATG) further delayed T cell recovery and increased BKV reactivation.
Conclusions:
- Pediatric haploidentical HSCT with PTCy is associated with delayed immune reconstitution and a higher risk of viral reactivation compared to HLA-matched HSCT.
- The use of ATG in conjunction with PTCy exacerbates T cell recovery delay and elevates the risk of BKV reactivation.
Introduction:
Immune reconstitution (IR) kinetics of paediatric patients underwent haploidentical haematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCy) have not been extensively studied. We compared IR patterns of children receiving HSCT from haploidentical (n = 92) and HLA-matched donors (n = 36), and analysed risk factors for viral infection in these patients.
Methods:
We prospectively measured lymphocyte subset numbers before HSCT and at 1, 3, 6 and 12 months after HSCT. Blood cytomegalovirus (CMV), Epstein-Barr virus, adenovirus, BK virus (BKV) and urine adenovirus and BKV viral loads were measured at designated time points.
Results:
The median numbers of total T and T helper cells at 1 month were significantly lower in the haploidentical group compared with the HLA-matched group. Haploidentical HSCT recipients had significantly lower median numbers of several T cell subsets and B cells for 1 year after HSCT. The median NK cell count of the haploidentical group was lower at 1 month. BKV haemorrhagic cystitis, blood CMV and urine adenovirus reactivation were more frequently found in the haploidentical group. Post-haploidentical HSCT patients receiving anti-T lymphocyte globulin (ATG) had significantly lower median numbers of total T cells (at 1 month) and T helper cells (at 6 and 12 months) and higher rate of blood BKV reactivation compared with those without ATG.
Conclusion:
Paediatric patients who undergo haploidentical HSCT with PTCy are likely to have delayed IR and an increased risk of viral reactivation/infection compared with HLA-matched HSCT. The addition of ATG to PTCy delayed T cell recovery and increased risk of BKV reactivation.
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