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