Significant Growth in HCT Use for Haemoglobinopathies in the Last Decade Driven By Sickle Cell Disease across All Ages with Excellent Outcomes: An Analysis of EBMT Haemoglobinopathies Working Party

Background: Allogeneic haemopoietic cell transplantation (HCT) is a well-established curative treatment modality for transfusion dependent thalassaemia (TDT) and sickle cell disease (SCD) (Baronciani, BMT 2016; de la Fuente, Lancet Hematology 2020). Significant population changes in high income countries and advances in conditioning regimens addressing both toxicity and donor availability have led to a wider application of HCT and generalized its use beyond HCT centres focused on its application. Conversely, the development of screening programmes and new therapeutic interventions is likely to have altered uptake. Whilst the real-world impact on HCT trends in the last decade is not known, it is of great importance for public policy.

Aims: We hypothesized significant changes in number and composition of transplants for haemoglobinopathies in the last decade.

Methods: The EBMT database was used to analyse the number of transplants from 2010 to 2021. Variable studied included the type of disease (TDT or SCD), year of transplantation, whether the recipient was of paediatric (up to 18 years of age) or adult , and 2-year overall survival (OS).

Results: A total of 4,622 first HCT procedures were completed for patients with haemoglobinopathies: 2,807 were carried out for TDT and 1,815 for SCD. 2,601 children with TDT underwent HCT at a median age of 6.7 years (IQR 3.8-10.8, range 0.5-18) whereas adults constituted 206 procedures at a median age of 22.1 years (IQR 10.6-26; range 18-44.8). 1,331 children with SCD underwent HCT at a median age of 9.6 years (IQR 6.3-13, range 1.1-18) whereas adults constituted 484 procedures at a median age of 26.5 years (IQR 21.3-32.2; range 18-49.2).

Whereas in the first year of analysis (2010) the number of HCT were 57 children (4.3% of total number across period for subgroup) and 4 adults (0.8%) for SCD and 204 children (7.8%) and 14 adults (6.8%) for TDT, at the end (2021), there were 170 children (12.8%) and 119 adults (24.4%) for SCD and 130 children (5%) and 8 adults for TDT (3.9%).

The overall number of transplants undertaken for haemoglobinopathies has almost doubled (n = 279 in 2010 vs n = 522 in 2021, 181% increase) over a decade despite the reduction seen during the pandemic. This is due to a 4.5-fold increase in the number of transplants for SCD whereas the number of transplants for TDT have not yet recovered to pre-pandemic levels and it follows a reducing trend since 2017. The increase in HCT for SCD has occurred across all ages but it is particularly marked for adults, 24.4% of all procedures occurring in the last year of study (2021).

With a median follow up of 2 years, the 2-years OS in patients transplanted for TDT was 92.1% (90.8-93.2) for children and 84.4% for adults (78.1-89); whereas for SCD it was 95.7% (94.3-96.7) for children and 93.7% for adults (901-95.7).

Conclusion: HCT for haemoglobinopathies has experienced a sustained growth in the last decade, driven by the number of procedures for SCD across all ages. In particular, the number of transplants for adults with SCD now constitutes 22% of all activity. This is underpinned by the lack of difference in the excellent overall outcomes between adult and children in SCD, despite recipients being older than in TDT.

de la Fuente:Vertex: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MAAT Pharma: Membership on an entity's Board of Directors or advisory committees; Sangamo: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Dalle:Teva: Current equity holder in private company; Vertex: Consultancy, Honoraria; Pierre Fabre Médicaments: Consultancy, Honoraria, Other: travels; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Symbiopharm: Consultancy, Honoraria; Orchard: Consultancy, Honoraria. Corbacioglu:Vertex Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Angelucci:BMS: Other: DMC; Vifor: Other: DMC; Regeneron: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Menarini: Honoraria, Speakers Bureau; Vertex: Other: DMC.