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

Abstract

SummaryWhen 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.

How to optimize outcome of patients undergoing HLA‐matched related haematopoietic stem cell transplantation in acquired and inherited bone marrow failure syndromes

“…In their paper, the authors report 5 the outcome of 32 children, aged ≤14 years, affected by aSAA ( n = 19) or non‐FA iBMFs ( n = 13) undergone allo‐HSCT from HLA 10/10 MRD after a reduced intensity non‐myeloablative conditioning regimen (RIC/NMA) with fludarabine (Flu) and a low dose of cyclophosphamide (Cy; 80 mg/kg cumulative dose) plus ATG (thymoglobulin, 10 mg/kg), leading to successful engraftment in all patients with a very low incidence of GvHD, resulting in a 3‐year OS and EFS of 95% and 93% respectively, that achieves 100% considering acquired SAA patients alone.…”