Improving Diagnosis in Idiopathic Cytopenia Using Gene Sequencing

Royal Marsden NHS Foundation Trust

Status: Unknown

Conditions: Cytopenia

Treatments: Procedure: Bone Marrow Aspirate

Study type: Observational

Funder types: Other

Identifiers

NCT03026751

CCR4384

Details and patient eligibility

About

10% of the cases referred to the specialist diagnostic haemato-pathology service at RMH are for cytopenias.

The hypothesis to be tested is that a proportion of patients with idiopathic cytopenias have mutations in myelodysplasic syndrome (MDS)-associated genes. The investigators will sequence a panel of known MDS-associated genes in patient material (bone marrow and blood) that is sent routinely to the diagnostic service where conventional techniques have failed to establish a clear diagnosis. 200 patients with idiopathic cytopenia will be followed up to determine their survival, blood counts and development of acute leukaemia and other haematological malignancies. The clinical outcomes will be correlated with any mutations detected.

Full description

Patients with cytopenias will be identified by their local District General Consultant haematologist and consent obtained. A bone marrow sample will be sent to RMH as per usual diagnostic pathway.

Once received at the RMH, an aliquot will be frozen down for sequencing by the Molecular Pathology lab. Only those cases of cytopenia without a specific diagnosis will be the focus of this study.

Results will be fed back to referring consultants with caveats regarding significance.

Patients will undergo telephone follow up and data will also be provided by local consultants.

The investigators will look at overall survival, development of haematological malignancies and full blood count. This will occur annually.

Enrollment: 285 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed informed consent
• Patients >= 18 years old
• Life expectancy more than 12 months
• Cytopenia defined as Hb < 110g/L and/or Neutrophils <1.5 x109/L and/or Platelets <100 x109/L

Exclusion criteria

• Known haematological malignancy or aplastic anaemia/paroxysmal nocturnal haemoglobinuria
• Cytopenia of known aetiology (after examination of blood film and other investigations have occurred). These include haematinic deficiency (patients unresponsive to appropriate haematinic deficiency may enter the study), autoimmune cytopenias, chronic renal anaemia (for those with isolated anaemia), known haemoglobinopathy (for those with isolated anaemia), chronic viral diseases (Hep B/C/HIV), cytopenias associated with liver disease, cytopenias associated with systemic autoimmune conditions (eg SLE, rheumatoid arthritis), anaemia of chronic disease (for those with isolated anaemia).
• Cytotoxic chemotherapy or other myelosuppressive drugs or radiotherapy within 12 months
• Inadequate bone marrow sample for gene testing