HLA-Haploidentical Transplantation in Children with Primary Immunodeficiency Using Post Cyclophosphamide

Haploidentical donor can be considered as an alternative source of stem cells for primary immune deficiencies (PIDs) who does not have a full matched donor. Due to toxicity of Post Cy, the dose is reduced from 50mg/kg on day 3 and 5 to 25mg/kg.METHODS: Fifteen (15) pediatric (age at transplant <14 years) PID patients underwent HSCT from October 2019 to May 2023 using a haploidentical HLA donor at our institution. Primary indications for transplantation included Severe Combined Immune Deficiency (SCID) in 12(80%) and, Chronic Granulomatous Disease, Omenn Syndrome and Wiskot Aldrich disease in one (6.7%) each. Conditioning regimen was ATG/Busulfan/Fludarabine/Thiotepa in 8(53.3%), ATG/Fludarabine/Thiotepa/Treosulfan in 3(20.0%), Busulfan/Fludarabine/Thiotepa in 1(6.7%), ATG/Busulfan/Fludarabine in 2(13.3%), followed by ATG/Busulfan/Cyclophosphamide/Thiotepa in 1(6.7%). Source of stem cells was bone marrow (BM) in 10(67.7%) and PBSC in 5(33.3%). Median CD34+ cell dose for BM was 8.84 × 10^6 per kg (range, 4.56-12.8) and for PBSC was 10.0 × 10^6 per kg.RESULTS: Fourteen patients (n=14,93.3%) had successful ANC engraftment with a median time to ANC recovery of 14 days (range, 13-16).Median time to platelets recovery was 26 days (range, 16-69). In terms of chimeric studies measured on day+100 in 14 patients, all but one were maintaining 100%donor chimerism. Acute GVHD was seen in 26.7%(n=12). No chronic GVHD was recorded.During day+100, hypertension was seen in 9(60.0%), SOS/VOD 4(26.7%), CMV reactivation in 4(26.7%), hemorrhagic cystitis in 2(13.3%), mucositis in 2(13.3%; both grade 2) and interstitial pneumonia in 1(6.7%). No seizures were observed. Bacterial infection were recorded in 6 (40.0%), fungal in 2(13.3%) and viral in 1(6.7%).At a median follow-up of 29.1 months and mortality rate of 20.0%, three-year overall survival is 80.0%(±10.3%). All 12 alive patients, were maintaining their graft.Preliminary outcome data on our cohort of immunodeficiency patients who underwent HSCT using haploidentical donor with reduced post-Cy dose is encouraging.