Diagnostic evaluation in bone marrow failure disorders: what have we learnt to help inform the transplant decision in 2024 and beyond?

ABSTRACT

Aplastic anemia (AA) is the prototypical bone marrow failure syndrome. In the current era of readily available 'molecular annotation', application of comprehensive next-generation sequencing panels has generated novel insights into underlying pathogenetic mechanisms, potentially leading to improvements in personalized therapeutic approaches. New evidence has emerged as to the role of somatic loss of HLA class I allele expression in 'immune-mediated' AA, associated molecular aberrations, and risk of clonal evolution. A deeper understanding has emerged regarding the role of 'myeloid' gene mutations in this context, translating patho-mechanistic insights derived from wider clinical and translational research within the myeloid disorder arena. Here, we review contemporary 'tools' which aid in confirmation of a diagnosis of AA, with an additional focus on their potential in guiding therapeutic options. A specific emphasis is placed upon interpretation and integration of this detailed diagnostic information and how this may inform optimal transplantation strategies.