Improving Diagnosis in Idiopathic Cytopenia Using Gene Sequencing

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Improving Diagnosis in Idiopathic Cytopenia Using Gene Sequencing

Conditions
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Cytopenia

Intervention / Treatment
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* Procedure: Bone Marrow Aspirate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Bone Marrow Aspirate|Bone marrow aspirate|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with idiopathic cytopenia with a mutation |  | 5 years |