Immune Reconstitution Following TCRαβ/CD19-Depleted Hematopoietic Cell Transplantation for Hematologic Malignancy in Pediatric Patients: Immune Reconstitution Following TCRαβ/CD19-Depleted HCT

ABSTRACT Background TCRαβ/CD19-depleted HCT has been used with excellent outcomes in pediatric patients with hematologic malignancies, and several studies have demonstrated rapid immune reconstitution in the nonmalignant setting. However, immune recovery following TCRαβ/CD19-depleted HCT for malignancy remains incompletely elucidated. Furthermore, the majority of studies to date have used haploidentical and matched unrelated donors. We report here results of immune reconstitution following TCRαβ/CD19-depleted HCT for hematologic malignancy in 51 pediatric patients where the majority of patients received grafts from unrelated donors. Methods Fifty-one pediatric patients with hematologic malignancies were enrolled. Grafts were from matched unrelated (n=20), mismatched unrelated (n=20) and haploidentical (n=11) donors. Median CD34+ cell dose was 10.2 × 106/kg (range 4.54-20), and median TCRαβ+ cell dose was 2.53 × 104/kg (range 0-44.9). Conditioning was myeloablative with either busulfan or total body irradiation, cyclophosphamide, and thiotepa. Thirty-three patients also received rabbit anti-thymocyte globulin. No prophylactic post-transplant immune suppression was routinely given. Forty-three patients received rituximab on day +1 for recipient positive Epstein-Barr virus serology. Results Forty-nine (96%) patients engrafted with a median time to neutrophil recovery of 13 days (range 8-30). Thirty-seven (73%) patients are alive at a median follow-up of 25 months (range 6-50). Nine (18%) patients developed Grade II-IV acute GVHD, and 5 (11%) patients developed extensive chronic GVHD. Twenty-six (51%) patients experienced viral reactivation. T cell reconstitution was rapid with significant numbers of CD3+, CD4+ and CD8+ T cells present on first assessment 4 months post-HCT, and significant numbers of naive CD4+ T cells were present by 8 months post-HCT. Chronic GVHD was associated with delayed T cell recovery; however, T cell reconstitution was not affected by underlying diagnosis, donor source, TCRαβ+ T cell dose, conditioning regimen, or use of anti-thymocyte globulin. B cell recovery mirrored T cell recovery, and IVIG was discontinued at a median of 8 months (range 4-22) post-HCT in patients alive and relapse-free at last follow-up. Conclusion Immune reconstitution is rapid following TCRαβ/CD19-depleted HCT in pediatric patients with hematologic malignancies. Donor graft source, haploidentical or unrelated, did not affect immune reconstitution. Viral reactivation is common in the first 100 days post-HCT, indicating that improved T cell defense is needed in the early post-HCT period.