Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in relapsed/ refractory follicular lymphoma

Paediatric myelodysplastic syndromes (MDS) are stem cellclonal disorders characterised by ineffective haematopoie-sis, presenting as chronic cytopenias and an increasedrisk of progression to acute myeloid leukaemia (AML).Interestingly, 10%–30% of children with paediatric MDShave pathogenic germline predisposition to AML and maypresent with multisystem syndromic anomalies. In the ab-sence of a pathogenic molecular abnormality, many chil-dren with cytopenias remain without a unifying diagnosisor management plan. In order to address this area of unmetclinical need, we established a national study, also supportedby a BSH cohort grant, in order to: 1. document the true in-cidence of these conditions in children in the UK; 2. cap-ture their clinical characteristics and response to treatment;and 3. perform genomic characterisation of these patients inorder to identify the molecular drivers for this heterogene-ous rare cohort of patients.Methods/Project Description: Paediatric patients withsuspected MDS were recruited through the UK paediatricMDS-JMML study, open in 18 tertiary paediatric haematol-ogy centres. Patients with a new diagnosis were prospectivelyrecruited to the study and serial clinical data and samplesfrom diagnosis to relapse were collected. A targeted next-generation sequencing (NGS) panel was used for the de-tection of known disease-driver mutations and, in selectedcases, whole-genome sequencing (WGS) was also utilised,following appropriate parental consent.Results: One hundred and twenty-four children, with adiagnosis of suspected MDS were recruited to the studyfrom 2015 to date. Following central review of the diagnos-tic investigations, 47 cases (38%) were identified to have denovo MDS; 12/124 (9.7%) cases presented with AML on thebackground of MDS; 5/124 cases developed dysplasia on thebackground of an inherited BM failure syndrome (4%); and2/124 cases presented as secondary MDS. Four cases pre-senting as suspected MDS eventually received other diagno-ses: Pearson’s syndrome (n = 2), XIAP deficiency (n = 1) andWiskott–Aldrich syndrome (n = 1). The remaining 54/124children (43.5%) were identified to have sustained cytope-nias, BM dysplasia, requiring frequent supportive care suchas transfusions, with no MDS associated mutations identi-fied through NGS.

https://clin.larvol.com/abstract-detail/BSH 2024/70982125