Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant

Abstract

SummaryThis study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0-12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen-matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0Á18). Event-free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0Á001). Ninety-one of 167 patients (55%) failed front-line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up-front (P 0Á017). Rejection was 2% for MFD HSCT and HSCT post-IST failure (P 0Á73). Acute graft-versus-host disease (GVHD) grade II-IV was 8% in MFD graft vs. 25% for HSCT post-IST failure (P < 0Á0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post-IST failure (P < 0Á0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first-line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option.

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

“…The finding of younger age as associated with a better outcome is in line with two recent large EBMT studies that showed OS rates of 83% and of 78%, respectively, in children and adolescents undergoing UD HSCT after failed IST. 19,20 Moreover, it is of interest that previous reports identified a significant age cut off of 20 years for UD allo-HSCT. 16,21 In the EBMT series, 3 Bacigalupo et al showed that, in the context of global improvement of transplantation procedures and outcomes, an age cut off of 27 years could not predict OS, underlining the need to reassess the age limit in this context.…”

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

“…Further, clonal transformation to myelodysplasia represents a serious complication of IST. The EBMT study reported a 3-year event-free survival after IST in children with AA of just 33 %, with 55 % of patients failing front-line IST and requiring rescue HSCT [6]. Therefore, the use of predictive biomarkers for identifying patients suitable for up-front Abstract The decision to select hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST) as initial therapy in acquired aplastic anemia (AA) is currently based on patient age and the availability of a human leukocyte antigen (HLA)-matched donor.…”

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

“…For those children lacking a matched sibling donor, immunosuppressive therapy (IST) with horse antithymocyte globulin (ATG) and ciclosporin is considered first-line therapy (Marsh et al, 2009). However, a recent study on the outcome of 563 children with SAA has demonstrated that event-free survival (EFS) at 3 years post-IST is sub-optimal at only 33%, with an overall failure rate of 55% (Dufour et al, 2015a). Rescue HLAmatched unrelated donor bone marrow transplant (MUD BMT) in those children who failed IST resulted in an overall survival (OS) of 78% and EFS of 71%, outcomes that were similar to that achieved with SIB BMT.…”

“…Transplant-related morbidity and mortality were minimal. 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.…”