Outcomes of children with haematological malignancies given second haploidentical haematopoietic stem cell transplantation with either TCRαβ/CD19 depletion or post‐transplant cyclophosphamide

Human leukocyte antigen (HLA)-haploidentical haematopoietic cell transplantation (haplo-HCT) is a suitable salvage strategy in children with haematological malignancies experiencing either relapse or graft failure (GF) after the first HCT. Data comparing outcomes of transplant strategies using either TCRαβ/CD19 depletion (TCRαβ) or post-transplant cyclophosphamide (PTCy) are currently lacking. This retrospective, multicentre study included children with haematological malignancies who received a second haplo-HCT, in which either TCRαβ depletion or PTCy was used as the graft-versus-host disease (GvHD) prophylaxis strategy. Primary outcomes included overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM). Overall, 123 patients were analysed, 56 receiving PTCy and 67 receiving TCRαβ. Median age at transplant was 9.1 years (range, 1.0–24.7 years). Relapse and GF were the transplant indications in 96 and 27 patients respectively. The 24-month OS [56.8% (95% CI: 42.5%–71.1%) vs. 43.2% (95% CI: 31.4%–55.1%)] and EFS [44.1% (95% CI: 30.3%–57.8%) vs. 35.8% (95% CI: 24.3%–47.3%)] did not differ between PTCy or TCRαβ cohorts. The CIR [34.0% (95% CI: 23.1%–50.1%) vs. 37.3% (95% CI: 27.3%–50.8%), p = 0.28] and NRM [18.9% (95% CI: 10.7%–33.4%) vs. 25.3% (95% CI: 16.8%–38.2%), p = 0.48] were comparable. Cumulative incidence of 100-day of any-grade acute GvHD was higher in the PTCy cohort [55.3% (95% CI: 43.7%–70.4%) vs. 32.8% (95% CI: 23.3%–46.2%), p = 0.02], with non-statistically significant differences for grade II–IV and grade III–IV. The 24-month cumulative incidence of chronic GvHD was higher in the PTCy cohort [38.8% (95% CI: 27.6%–54.6%) vs. 11.9% (95% CI: 6.2%–22.8%), p < 0.01], including moderate–severe forms [15.3% (95% CI: 8.1%–29.1%) vs. 1.4% (95% CI: 0.2%–10.4%), p < 0.01]. Infectious complications were comparable except for a higher adenovirus reactivation rate in the TCRαβ group (14.3% vs. 29.9%, p = 0.04). PTCy and TCRαβ offer comparable clinical outcomes in the setting of second haplo-HCT, although PTCy is associated with a higher incidence of GvHD and lower adenovirus reactivation.