Recurrent bacterial infections, but not fungal infections, characterise patients with ELANE‐related neutropenia: a French Severe Chronic Neutropenia Registry study

Abstract

Among 143 patients with elastase, neutrophil-expressed (ELANE)-related neutropenia enrolled in the French Severe Chronic Neutropenia Registry, 94 were classified as having severe chronic neutropenia (SCN) and 49 with cyclic neutropenia (CyN). Their infectious episodes were classified as severe, mild or oral, and analysed according to their natural occurrence without granulocyte-colony stimulating factor (G-CSF), on G-CSF, after myelodysplasia/acute leukaemia or after haematopoietic stem-cell transplantation. During the disease's natural history period (without G-CSF; 1913 person-years), 302, 957 and 754 severe, mild and oral infectious events, respectively, occurred. Among severe infections, cellulitis (48%) and pneumonia (38%) were the most common. Only 38% of episodes were microbiologically documented. The most frequent pathogens were Staphylococcus aureus (37Á4%), Escherichia coli (20%) and Pseudomonas aeruginosa (16%), while fungal infections accounted for 1%. Profound neutropenia (<200/ mm 3 ), high lymphocyte count (>3000/mm 3 ) and neutropenia subtype were associated with high risk of infection. Only the p.Gly214Arg variant (5% of the patients) was associated with infections but not the overall genotype. The first year of life was associated with the highest infection risk throughout life. G-CSF therapy achieved lower ratios of serious or oral infectious event numbers per period but was less protective for patients requiring >10 µg/kg/day. Infections had permanent consequences in 33% of patients, most frequently edentulism.

Inborn Errors of Immunity Causing Pediatric Susceptibility to Fungal Diseases

“…In this regard, IC has been reported in patients with congenital neutropenia syndromes (ELANE, HAX1, etc.) [ 78 ] and leukocyte adhesion disorders 1 (LAD-1, ITKB2) [ 79 ]. Similarly, complete myeloperoxidase (MPO) deficiency or chronic granulomatous disease (CGD) have been associated with deep-seated Candida infections [ 80 , 81 , 82 ].…”

ELANE neutropenia and solid tumors: Four cases from the French severe chronic neutropenia registry

“…As of April 31, 2021, the French severe chronic neutropenia registry included 147 patients with ELANE-N. 3 The World Health Organization classification of cancers was applied during a centralized review of the tumor samples. ELANE-N variants were identified and cancersusceptibility genes were studied by a 112 genes panel (Table 1, Panel #1).…”

“…As of April 31, 2021, the French severe chronic neutropenia registry included 147 patients with ELANE‐N 3 . The World Health Organization classification of cancers was applied during a centralized review of the tumor samples.…”

Chronic neutropenia: how best to assess severity and approach management?

“…According to evidence-based methodology, the grade of evidence is extremely low and, to the best of our best knowledge, we may have identified only one randomized study that evaluated the impact of Granulocyte-Colony Stimulating factor (GCSF) in chronic neutropenia [1], and the number of cohort studies that included more than 100 patients and focused on aspects of monogenic neutropenia was <15 [2][3][4][5][6][7][8][9][10][11][12][13][14]. This underlines the real difficulties in collecting data and organizing clinical trials and cohorts in this medical area, and explains why many clinical decisions are still based on expert opinion, rather than large cohort studies.…”

“…There are also many situations in which the neutropenia, including very profound neutropenia, has minimal or no infectious consequence because the overall total body neutrophil count is not affected. At contrary, ELANE neutropenia can be considere as a model of 'pure' chronic neutropenia and data from a cohort of such patients display a overview of the typology of infections which may occur in neutropenia patients [14]. The most frequent sites are mucocutaneous; ear, nose, and throat; and pulmonary.…”