Background Our centre performed the first ex-vivo T-lymphocyte depleted (TCD) haploidentical allograft in 1987 in a child with PID. Different TCD methods have been used including CAMPATH-1M TCD marrow (n=34), CD34+ selected marrow (CD34-S, n=34), CD3/CD19 TCD PBSC (n=7), and CD3-TCRαβ/CD19 TCD PBSC (αβ-TCD, n=30)). This study aimed to examine transplant outcomes according to different methods in children with PID. Methods Between Jan 1987 and Mar 2019, 105 PID patients underwent first TCD allograft and were included in the study. Thirteen patients who received gene-modified add-back T cells were excluded. The main outcomes of interest were OS, EFS and graft failure. An event was defined as death, graft failure or second procedures for slipping chimerism. Other endpoints were neutrophil engraftment, GvHD, immune reconstitution and donor chimerism. Log-rank test was used to compare OS and EFS according to TCD methods. Cumulative incidences (CI) graft failure was calculated using a competing risk analysis, considering death as a competing event. Multilevel mixed effects modelling was performed for the longitudinal analysis of immune reconstitution and CAMPATH-1M was used as a reference group. Results Donors were haploidentical donor (n=84, 83%), MUD/MFD (n=9, 9%) and MMFD/MMUD (n=8, 8%). 94% received conditioning. Thirteen (12%) patients had aGvHD, of whom 3 had grade III-IV. None had cGvHD. The cause of death changed from predominantly infection (18/25, 72%) in CAMPATH-IM and CD34-S to non-infectious causes in all 6 deaths in CD3/CD19 and αβ-TCD. Analysis by TCD methods revealed a 5-year OS of 58% (95% CI, 40-73%) for CAMPATH-1M, 68% (49-81%) for CD34-S, 69% (22-91%) for CD3/CD19 TCD and 83% (61-93%) for (αβ-TCD (p=0.24). Age was a significant predictor of OS for non-SCID PID (p=0.02). The corresponding EFS was 46% (29-62%) for CAMPATH-1M, 47% (30-62%) for CD34-S, 69% (95% CI, 22-91%) for CD3/CD19 TCD and 83% (61-93%) for αβ-TCD (p=0.04) (Fig 1B) The CI of graft failure reduced significantly, from 29% (14-61%) for CAMPATH-1M, to 19% (95%CI, 8-45%) for CD34-S, 17% (2-18%) for CD3/CD19 TCD and none had graft failure in αβ-TCD (p=0.002) (Figure 1C). CD4+ lymphocytes were significantly higher in CD34-S at months 4 (p=0.02), 5 (p=0.01), and 6 (p=0.006) post-HCT and at month 4 (p=0.04) post-HCT in αβ-TCD when compared to CAMPATH-1M (Fig 1D). The median donor myeloid chimerism at last follow-up was higher in newer TCD; 100% (range, 0-100%) for αβ-TCD, 93% (0-100%) for CD3/CD 19 depletion, 6% (0 -49%) for CD34-S, 20% (0-100%) for CAMPATH-1M (p Conclusions Outcomes after CD3+TCR αβ/CD19+ depletion are superior to previously used TCD methods. In an experienced centre it is a safe alternative procedure and enables a wide spectrum of PID to be transplanted. The result has led to evolution of donor hierarchy in our centre.