Isolated leukopenia in children and adolescents referred to a Pediatric Hematology Clinic

Aim: Pediatric isolated leukopenia (IL) includes multiple conditions but data to guide evaluation of children and adolescents are scarce. The aim of this study was to investigate the underlying diagnoses of IL in a cohort of children and adolescents referred to our Clinic. Methods: Retrospective analysis of 134 consecutive patients with IL, evaluated and followed-up in a Pediatric Hematology Outpatient Clinic. Firstlevel investigations included complete blood count (CBC) with differential, mean corpuscular volume (MCV), and fetal hemoglobin. Results: IL resolved in 50 subjects (37.3%). Seventy-two children (53.7%) were classified as having idiopathic leukopenia. Resolution was less likely if patients presented with more than 1 abnormality at first-level hematological investigations at the time of referral. Molecular analyses identified potential disease-causing variants in 6.7% of the patients. Autoimmune disorders (AID) and clinical primary immunodeficiencies (cPID) were common (10.4% and 9.7%, respectively). Five patients (3.7%) ultimately developed a myelodysplastic syndrome (MDS). Patients with monocytopenia and increased MCV had higher risk of developing MDS (p = 0.0002 and p = 0.0001, respectively). Conclusions: In case of recent infection without monocytopenia, increased MCV or multiple CBC abnormalities, post-infectious IL is frequent and white blood cells (WBC) fully recover. A consistent number of patients had underlying AID or cPID. Whenever leukopenia persists beyond 12 months, molecular analyses should be performed and a clonal hematopoietic disorder should be excluded.