Long-lasting, late-onset, and chronic idiopathic neutropenia project

An SWG Grant-supported project initiated by EHA's SWG on Granulocytes and Constitutional Marrow Failure Disorders.

Project team

Dr Francesca Fioredda Dr Francesca Fioredda

Senior Hematologist
Giannina Gaslini Children's Hospital

Dr Grigorios Tsaknakis Dr Grigorios Tsaknakis

Post-doctoral researcher, Prof Dr Helen Papadaki’s Haemopoiesis Research Lab, School of Medicine
University of Crete

Project background and aims

This SWG Grant-funded project will help to support an increased knowledge of LLNp, LONp, and CIN.

Neutropenia is a condition that affects the amount of neutrophils in a person's blood. It means they have a low number of these white blood cells.

There are two types of neutropenia that are not categorized as either primary autoimmune neutropenia or the idiopathic neutropenia of infancy. These are:

  • Long-lasting neutropenia (LLNp)—which is a type of neutropenia that lasts for more than the typical period of 24 to 36 months
  • Late-onset neutropenia (LONp)—which is a type of neutropenia that has a delayed or a very delayed onset

Both of these types of neutropenia:

  • Are sometimes diagnosed by chance, due to the very mild clinical phenotype
  • Do not usually show remission

As shown in a recent paper from our group, both of these forms might be considered as a unique entity that's sustained, at least in a little subgroup, by an underlying genetic background.

In both cases, patients show signs of immune dysregulation. This may be present at the beginning, with a tendency to worsen over time (leukopenia, lymphopenia with decreased B and NK cell numbers).

We could speculate that, because they present few symptoms, neutropenias that arise in late infancy or adolescents may be under-diagnosed until adulthood. At that point, they will present as chronic idiopathic neutropenia (CIN).

If this hypothesis is correct, there could be a link that joins neutropenia in children with neutropenia in adults. In this view, any collaboration between pediatricians and adult hematologists is of outstanding importance.

This SWG Grant-funded project will help to create the basis of that connection by supporting increased knowledge of LLNp, LONp, and CIN. In particular, it will provide information on their:

  • Clinical and immunological features
  • Genetic background—through the application of the whole-exome sequencing (WES) technique

By furthering knowledge on LLNp, LONp, and CIN, we can help clinicians to:

  • Understand the underlying mechanisms of these disorders
  • Tailor diagnostic work-ups
  • Manage all affected patients more appropriately

‘Our research hypothesis is that:

  • A constitutional/congenital background might exist in some CIN cases
  • The CIN phenotype can be also an epiphenomenon of immune dysregulation and associated underlying disorders

This grant will significantly contribute towards delineating the pathogenesis of CIN through the:

  • Identification of variants with high probability to display a causative role
  • Indication of a potential continuum in the spectrum of CIN from childhood to adulthood, at least in some cases
  • Identification of cases with common genetic background'

— Dr Grigorios Tsaknakis