Paediatric B-lymphoblastic leukaemia with low peripheral blasts: a potential diagnostic pitfall

B cell acute lymphoblastic leukaemia (B-ALL) infrequently presents with undetectable or very low peripheral blood (PB) lymphoblasts, which may cause diagnostic difficulties. We report the clinicopathological features of paediatric patients with B-ALL who presented with low (<5%; n=31) PB lymphoblasts by flow cytometry. 15 patients presented with <1% PB lymphoblasts (range: 0.0%-0.9%), a level potentially undetectable by manual smear review and standard 100-cell count. Compared with patients presenting with ≥5% PB lymphoblasts (n=45), those with <5% had more frequent musculoskeletal symptoms, less frequent lymphadenopathy and hepatosplenomegaly, higher platelet counts, lower white blood cell counts and lower lactate dehydrogenase. The presence of low PB lymphoblasts was associated with favourable cytogenetics (ETV6::RUNX1 or high hyperdiploidy without IKZF1 deletion) and less frequent central nervous system involvement. Aleukemic/low PB lymphoblast presentation of B-ALL is associated with unique clinicopathological features that overlap with non-malignant disorders. A high degree of clinical suspicion and careful review of PB flow cytometry data are required for timely diagnosis.