Comparing between HLA-matched sibling donor allogenic HSCT and non-sibling matched related donor allogenic HSCT outcome in pediatric patients; single center retrospective study.

BACKGROUND: Extended family donor search other than siblings may yield an HLA matched donor in communities with high rate of consanguinity. The outcome of patients who are transplanted from non-sibling matched related donors (NS-MRD) including engraftment and graft versus host disease (GVHD) are scarce in comparison with matched sibling donor (MSD). METHODS: We retrospectively reviewed the outcome of all our pediatric hematopoietic stem cell transplantation (HSCT) patients who had non-sibling matched related donor and controlled them with matched sibling donor HSCT (based on age, indication of HSCT, conditioning regimen, GVHD prophylaxis, serotherapy, stem cell source and cytomegalovirus status). RESULTS: A total of 76 patients were reviewed during study period. Thirty patients (39.5%) in NS-MRD arm and 46 patients in MSD (60.5%) were identified after matching in age, disease, and conditioning regimens. All patients had similar approach including stem cell source and GVHD prophylaxis (CNI + 2nd agent). Out of the NS-MRD group, 18 patients (59%) had one of their parents as a donor and the rest as second degree relatives. Both groups were equally distributed and were homogeneous. Both groups had no statistically significant difference in outcome including engraftment, GVHD and Chimerism tests results. GVHD was seen in (13%) NS-MRD patients compared to (11%) in MSD patients. All patients remain alive with median follow up of 1249 days (431-3525). CONCLUSIONS: This study showed no significant difference in allogenic HSCT outcomes between matched sibling donors and non-sibling matched related donors and support using the same management approach in terms of conditioning therapy, GVHD prophylaxis, and serotherapy only if indicated.

Human leucocyte antigen-matched related haematopoietic stem cell transplantation using low-dose cyclophosphamide, fludarabine and thymoglobulin in children with severe aplastic anaemia.

When human leucocyte antigen-matched related donors are available, haematopoietic stem cell transplantation (HSCT) in children with severe aplastic anaemia (SAA) represents the standard of care. Cyclophosphamide (Cy) 200 mg/kg and anti-thymocyte globulin (ATG) are frequently administered, but to-date, no standard conditioning regimen exists. In this study, we investigated the efficacy of a unified HSCT conditioning protocol consisting of low-dose Cy 80 mg/kg, fludarabine and ATG. Data were reviewed from children aged ≤14 years with either acquired SAA or non-Fanconi anaemia inherited bone marrow failure syndrome (IBMFS) between 2011 and 2022 at various Saudi institutions. Graft-versus-host disease (GVHD) prophylaxis included mycophenolate mofetil and calcineurin inhibitors. HSCT was performed in 32 children (17 females and 15 males). Nine patients had deleterious mutations (two ERCC6L2, two ANKRD26, two TINF2, one LZTFL1, one RTEL1 and one DNAJC21). Four patients had short telomeres. All 32 patients engrafted successfully. At 3 years post-transplant, the event-free survival was 93% and overall survival was 95%. Two patients experienced secondary graft failure or myelodysplastic syndrome. A low probability of GVHD was observed (one acute GVHD II and one mild chronic GVHD). These data highlight how HSCT using low-dose Cy as part of a fludarabine-based regimen is safe and effective in SAA/non-Fanconi anaemia IBMFS.