An assay for neutrophil-specific antibodies is frequently used in the workup of chronic severe neutropenia and is suggestive of autoimmune, or sporadically alloimmune neutropenia, rather than severe congenital neutropenia (SCN). We analyzed a neutropenia consortium database for the outcomes of antibody testing initiated before receiving genetic diagnosis in Polish SCN cohort. Test results, performed in a single reference laboratory, were available for 14 patients with ELANE-mutated SCN or cyclic neutropenia, and were frequently positive (36%). We note that the trigger for genetic studies in severe neutropenia should not be affected by antibody-positivity and should be clinically driven.

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Venetoclax, the best established BH3 mimetic, is a practice-changing proapoptotic drug to treat blood cancers in adults. In paediatrics, the data are less but exciting results were recently presented in relapsed or refractory leukaemias demonstrating significant clinical activity. Importantly, the interventions could be potentially molecularly guided as vulnerabilities to BH3 mimetics were reported. Currently, venetoclax is not incorporated into paediatric treatment schedules in Poland but it has been already used in patients that failed conventional therapy in Polish paediatric haemato-oncology departments. The aim of the study was to gather clinical data and correlates of all paediatric patients treated thus far with venetoclax in Poland. We set out to gather this data to help choose the right clinical context for the drug and stimulate further research. The questionnaire regarding the use of venetoclax was sent to all 18 Polish paediatric haemato-oncology centres. The data of November 2022 were gathered and analysed for the diagnoses, triggers for the intervention, treatment schedules, outcomes and molecular associations. We received response from 11 centres, 5 of which administered venetoclax to their patients. Clinical benefit, in most cases consistent with haematologic complete remission (CR), was reported in five patients out of ten, whereas five patients did not show clinical benefit from the intervention. Importantly, patients with CR included subtypes expected to show venetoclax vulnerability, such as poor-prognosis ALL with TCF::HLF fusion. We believe that BH3 mimetics have clinical activity in children and should be available to paediatric haemato-oncology practitioners in well-selected applications.

Congenital defects of neutrophil number or function are associated with a severe infectious phenotype that may require intensive medical attention and interventions to be controlled. While the infectious complications in inherited neutrophil disorders are easily understood much less clear and explained are autoimmune and autoinflammatory phenomena. We survey the clinical burden of autoimmunity/autoinflammation in this setting, search for common patterns, discuss potential mechanisms and emerging treatments.