Similar outcome of upfront‐unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT

Abstract

SummaryWe explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 AE 4% compared to 91 AE 3% in the MSD controls (P = 0Á30) and 94 AE 3% in the IST controls (P = 0Á68) and 74 AE 9% in the unrelated donor HSCT post-IST failure controls (P = 0Á02).The 2-year event-free survival in the upfront cohort was 92 AE 5% compared to 87 AE 4% in MSD controls (P = 0Á37), 40 AE 7% in IST controls (P = 0Á0001) and 74 AE 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0Á02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD.

In support of upfront stem cell transplantation as first‐line therapy for paediatric patients with idiopathic severe aplastic anaemia who lack a sibling donor

“…Similar to observations by Dufour et al (2015b), complications and morbidity post-transplant were minimal. Overall failure rate post-IST was 67%, with prolonged cytopenias and only partial remissions.…”

“…These findings prompted a study of MUD BMT as first line therapy in a UK cohort of 29 children with idiopathic SAA who lacked a matched sibling donor (Dufour et al, 2015b). Compared to historical matched controls, upfront MUD BMT was demonstrated to have superior results to first line IST and to MUD BMT performed following failure of IST, with a similar OS (96% vs. 91%) and 2-year EFS (92% vs. 87%) as SIB BMT.…”

“…Although OS following IST has been very good in the paediatric population (83-94%, Dufour et al, 2015a;Yoshida et al, 2014), quality of life is significantly compromised by the restrictions imposed by prolonged cytopenias as a result of slow count recovery (at least 3-4 months in most cases), with the majority of children only achieving partial remissions (Joeng et al, 2014). Dufour et al (2015b) suggested that a change in the paediatric idiopathic SAA treatment algorithm should be instigated with consideration of upfront MUD BMT, when readily available, in place of IST in those without a matched sibling donor. With this in mind, we retrospectively examined the management, count recovery and outcomes of all children diagnosed in Ireland with SAA over a 15-year period.…”

Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party

“…7 Moreover, excellent UD allo-HSCT results were reported in children receiving in vivo T-cell depletion as part of their conditioning regimen, in the setting of both IST failure 8 and up-front treatment. 9 Together, these recent results suggest considering early UD allo-HSCT as a preferred option for younger patients who lack HLA-identical siblings, provided the graft be performed early after diagnosis. However, although the age limit for this procedure, the timing of UD allo-HSCT and the impact of HLA mismatch have been tested as singular factors, the combined effect of these variables during the natural history of the disease remains unclear.…”

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

“…In particular, young patients with disease duration of <1 year have achieved better results than adults did [40]. The EBMT group demonstrated that upfront matched or mismatched unrelated donor HSCT has similar outcomes to matched sibling donor HSCT in idiopathic severe AA of childhood and adolescence [41]. Further, a Japanese study found no differences in OS and FFS between matched sibling donor and unrelated donor HSCT [42].…”